A Finite Element Model of the THOR-K Dummy for Aerospace and Aircraft Impact Simulations

NASA Technical Reports Server (NTRS)

Putnam, Jacob; Untaroiu, Costin D.; Somers, Jeffrey T.; Pellettiere, Joseph

2013-01-01

1) Update and Improve the THOR Finite Element (FE) model to specifications of the latest mod kit (THOR-K). 2) Evaluate the kinematic and kinetic response of the FE model in frontal, spinal, and lateral impact loading conditions.

Magnetic resonance imaging of rodent spinal cord with an improved performance coil at 7 Tesla

NASA Astrophysics Data System (ADS)

Solis-Najera, S. E.; Rodriguez, A. O.

2014-11-01

Magnetic Resonance Imaging of animal models provide reliable means to study human diseases. The image acquisition particularly determined by the radio frequency coil to detect the signal emanated from a particular region of interest. A scaled-down version of the slotted surface coil was built based on the previous results of a magnetron-type surface coil for human applications. Our coil prototype had a 2 cm total diameter and six circular slots and was developed for murine spinal cord at 7 T. Electromagnetic simulations of the slotted and circular coils were also performed to compute the spatially dependent magnetic and electric fields using a simulated saline-solution sphere. The quality factor of both coils was experimentally measured giving a lower noise figure and a higher quality factor for the slotted coil outperforming the circular coil. Images of the spinal cord of a rat were acquired using standard pulse sequences. The slotted surface coil can be a good tool for spinal cord rat imaging using conventional pulse sequences at 7 T.

Development and validation of a subject-specific finite element model of the functional spinal unit to predict vertebral strength.

PubMed

Lee, Chu-Hee; Landham, Priyan R; Eastell, Richard; Adams, Michael A; Dolan, Patricia; Yang, Lang

2017-09-01

Finite element models of an isolated vertebral body cannot accurately predict compressive strength of the spinal column because, in life, compressive load is variably distributed across the vertebral body and neural arch. The purpose of this study was to develop and validate a patient-specific finite element model of a functional spinal unit, and then use the model to predict vertebral strength from medical images. A total of 16 cadaveric functional spinal units were scanned and then tested mechanically in bending and compression to generate a vertebral wedge fracture. Before testing, an image processing and finite element analysis framework (SpineVox-Pro), developed previously in MATLAB using ANSYS APDL, was used to generate a subject-specific finite element model with eight-node hexahedral elements. Transversely isotropic linear-elastic material properties were assigned to vertebrae, and simple homogeneous linear-elastic properties were assigned to the intervertebral disc. Forward bending loading conditions were applied to simulate manual handling. Results showed that vertebral strengths measured by experiment were positively correlated with strengths predicted by the functional spinal unit finite element model with von Mises or Drucker-Prager failure criteria ( R 2  = 0.80-0.87), with areal bone mineral density measured by dual-energy X-ray absorptiometry ( R 2  = 0.54) and with volumetric bone mineral density from quantitative computed tomography ( R 2  = 0.79). Large-displacement non-linear analyses on all specimens did not improve predictions. We conclude that subject-specific finite element models of a functional spinal unit have potential to estimate the vertebral strength better than bone mineral density alone.

Light distribution properties in spinal cord for optogenetic stimulation (Conference Presentation)

NASA Astrophysics Data System (ADS)

GÄ secka, Alicja; Bahdine, Mohamed; Lapointe, Nicolas; Rioux, Veronique; Perez-Sanchez, Jimena; Bonin, Robert P.; De Koninck, Yves; Côté, Daniel

2016-03-01

Optogenetics is currently one of the most popular technique in neuroscience. It enables cell-selective and temporally-precise control of neuronal activity. Good spatial control of the stimulated area and minimized tissue damage requires a specific knowledge about light scattering properties. Light propagation in cell cultures and brain tissue is relatively well documented and allows for a precise and reliable delivery of light to the neurons. In spinal cord, light must pass through highly organized white matter before reaching cell bodies present in grey matter, this heterogenous structure makes it difficult to predict the propagation pattern. In this work we investigate the light distribution properties through mouse and monkey spinal cord. The light propagation depends on a fibers orientation, leading to less deep penetration profile in the direction perpendicular to the fibers and lower attenuation in the direction parallel to the fibers. Additionally, the use of different illumination wavelengths results in variations of the attenuation coefficient. Next, we use Monte-Carlo simulation to study light transport. The model gives a full 3-D simulation of light distribution in spinal cord and takes into account different scattering properties related to the fibers orientation. These studies are important to estimate the minimum optical irradiance required at the fiber tip to effectively excite the optogenetic proteins in a desired region of spinal cord.

Discrepancies in anthropometric parameters between different models affect intervertebral rotations when loading finite element models with muscle forces from inverse static analyses.

PubMed

Zhu, Rui; Rohlmann, Antonius

2014-06-01

In only a few published finite element (FE) simulations have muscle forces been applied to the spine. Recently, muscle forces determined using an inverse static (IS) model of the spine were transferred to a spinal FE model, and the effect of methodical parameters was investigated. However, the sensitivity of anthropometric differences between FE and IS models, such as body height and spinal orientation, was not considered. The aim of this sensitivity study was to determine the influence of those differences on the intervertebral rotations (IVRs) following the transfer of muscle forces from an IS model to a FE model. Muscle forces were estimated for 20° flexion and 10° extension of the upper body using an inverse static musculoskeletal model. These forces were subsequently transferred to a nonlinear FE model of the spino-pelvic complex, which includes 243 muscle fascicles. Deviations of body height (±10 cm), spinal orientation in the sagittal plane (±10°), and body weight (±10 kg) between both models were intentionally generated, and their influences on IVRs were determined. The changes in each factor relative to their corresponding reference value of the IS model were calculated. Deviations in body height, spinal orientation, and body weight resulted in maximum changes in the IVR of 19.2%, 26% and 4.2%, respectively, relative to T12-S1 IVR. When transferring muscle forces from an IS to a FE model, it is crucial that both models have the same spinal orientation and height. Additionally, the body weight should be equal in both models.

A model of cerebrocerebello-spinomuscular interaction in the sagittal control of human walking.

PubMed

Jo, Sungho; Massaquoi, Steve G

2007-03-01

A computationally developed model of human upright balance control (Jo and Massaquoi on Biol cybern 91:188-202, 2004) has been enhanced to describe biped walking in the sagittal plane. The model incorporates (a) non-linear muscle mechanics having activation level -dependent impedance, (b) scheduled cerebrocerebellar interaction for control of center of mass position and trunk pitch angle, (c) rectangular pulse-like feedforward commands from a brainstem/ spinal pattern generator, and (d) segmental reflex modulation of muscular synergies to refine inter-joint coordination. The model can stand when muscles around the ankle are coactivated. When trigger signals activate, the model transitions from standing still to walking at 1.5 m/s. Simulated natural walking displays none of seven pathological gait features. The model can simulate different walking speeds by tuning the amplitude and frequency in spinal pattern generator. The walking is stable against forward and backward pushes of up to 70 and 75 N, respectively, and with sudden changes in trunk mass of up to 18%. The sensitivity of the model to changes in neural parameters and the predicted behavioral results of simulated neural system lesions are examined. The deficit gait simulations may be useful to support the functional and anatomical correspondences of the model. The model demonstrates that basic human-like walking can be achieved by a hierarchical structure of stabilized-long loop feedback and synergy-mediated feedforward controls. In particular, internal models of body dynamics are not required.

Transverse tripolar spinal cord stimulation: theoretical performance of a dual channel system.

PubMed

Struijk, J J; Holsheimer, J

1996-07-01

A new approach to spinal cord stimulation is presented, by which several serious problems of conventional methods can be solved. A transverse tripolar electrode with a dual-channel voltage stimulator is evaluated theoretically by means of a volume conductor model, combined with nerve fibre models. The simulations predict that a high degree of freedom in the control of activation of dorsal spinal pathways may be obtained with the described system. This implies an easier control of paraesthesia coverage of skin areas and the possibility to correct undesired paraesthesia patterns, caused by lead migration, tissue growth, or anatomical asymmetries, for example, without surgical intervention. It will also be possible to preferentially activate either dorsal column or dorsal root fibres, which has some important clinical advantages. Compared to conventional stimulation systems, the new system has a relatively high current drain.

Effect of spine motion on mobility in quadruped running

NASA Astrophysics Data System (ADS)

Chen, Dongliang; Liu, Qi; Dong, Litao; Wang, Hong; Zhang, Qun

2014-11-01

Most of current running quadruped robots have similar construction: a stiff body and four compliant legs. Many researches have indicated that the stiff body without spine motion is a main factor in limitation of robots' mobility. Therefore, investigating spine motion is very important to build robots with better mobility. A planar quadruped robot is designed based on cheetahs' morphology. There is a spinal driving joint in the body of the robot. When the spinal driving joint acts, the robot has spine motion; otherwise, the robot has not spine motion. Six group prototype experiments with the robot are carried out to study the effect of spine motion on mobility. In each group, there are two comparative experiments: the spinal driving joint acts in one experiment but does not in the other experiment. The results of the prototype experiments indicate that the average speeds of the robot with spine motion are 8.7%-15.9% larger than those of the robot without spine motion. Furthermore, a simplified sagittal plane model of quadruped mammals is introduced. The simplified model also has a spinal driving joint. Using a similar process as the prototype experiments, six group simulation experiments with the simplified model are conducted. The results of the simulation experiments show that the maximum rear leg horizontal thrusts of the simplified mode with spine motion are 68.2%-71.3% larger than those of the simplified mode without spine motion. Hence, it is found that spine motion can increase the average running speed and the intrinsic reason of speed increase is the improvement of the maximum rear leg horizontal thrust.

Mechanical Design and Analysis of a Unilateral Cervical Spinal Cord Contusion Injury Model in Non-Human Primates.

PubMed

Sparrey, Carolyn J; Salegio, Ernesto A; Camisa, William; Tam, Horace; Beattie, Michael S; Bresnahan, Jacqueline C

2016-06-15

Non-human primate (NHP) models of spinal cord injury better reflect human injury and provide a better foundation to evaluate potential treatments and functional outcomes. We combined finite element (FE) and surrogate models with impact data derived from in vivo experiments to define the impact mechanics needed to generate a moderate severity unilateral cervical contusion injury in NHPs (Macaca mulatta). Three independent variables (impactor displacement, alignment, and pre-load) were examined to determine their effects on tissue level stresses and strains. Mechanical measures of peak force, peak displacement, peak energy, and tissue stiffness were analyzed as potential determinants of injury severity. Data generated from FE simulations predicted a lateral shift of the spinal cord at high levels of compression (>64%) during impact. Submillimeter changes in mediolateral impactor position over the midline increased peak impact forces (>50%). Surrogate cords established a 0.5 N pre-load protocol for positioning the impactor tip onto the dural surface to define a consistent dorsoventral baseline position before impact, which corresponded with cerebrospinal fluid displacement and entrapment of the spinal cord against the vertebral canal. Based on our simulations, impactor alignment and pre-load were strong contributors to the variable mechanical and functional outcomes observed in in vivo experiments. Peak displacement of 4 mm after a 0.5N pre-load aligned 0.5-1.0 mm over the midline should result in a moderate severity injury; however, the observed peak force and calculated peak energy and tissue stiffness are required to properly characterize the severity and variability of in vivo NHP contusion injuries.

Simulating spinal border cells and cerebellar granule cells under locomotion--a case study of spinocerebellar information processing.

PubMed

Spanne, Anton; Geborek, Pontus; Bengtsson, Fredrik; Jörntell, Henrik

2014-01-01

The spinocerebellar systems are essential for the brain in the performance of coordinated movements, but our knowledge about the spinocerebellar interactions is very limited. Recently, several crucial pieces of information have been acquired for the spinal border cell (SBC) component of the ventral spinocerebellar tract (VSCT), as well as the effects of SBC mossy fiber activation in granule cells of the cerebellar cortex. SBCs receive monosynaptic input from the reticulospinal tract (RST), which is an important driving system under locomotion, and disynaptic inhibition from Ib muscle afferents. The patterns of activity of RST neurons and Ib afferents under locomotion are known. The activity of VSCT neurons under fictive locomotion, i.e. without sensory feedback, is also known, but there is little information on how these neurons behave under actual locomotion and for cerebellar granule cells receiving SBC input this is completely unknown. But the available information makes it possible to simulate the interactions between the spinal and cerebellar neuronal circuitries with a relatively large set of biological constraints. Using a model of the various neuronal elements and the network they compose, we simulated the modulation of the SBCs and their target granule cells under locomotion and hence generated testable predictions of their general pattern of modulation under this condition. This particular system offers a unique opportunity to simulate these interactions with a limited number of assumptions, which helps making the model biologically plausible. Similar principles of information processing may be expected to apply to all spinocerebellar systems.

From the motor cortex to the movement and back again.

PubMed

Teka, Wondimu W; Hamade, Khaldoun C; Barnett, William H; Kim, Taegyo; Markin, Sergey N; Rybak, Ilya A; Molkov, Yaroslav I

2017-01-01

The motor cortex controls motor behaviors by generating movement-specific signals and transmitting them through spinal cord circuits and motoneurons to the muscles. Precise and well-coordinated muscle activation patterns are necessary for accurate movement execution. Therefore, the activity of cortical neurons should correlate with movement parameters. To investigate the specifics of such correlations among activities of the motor cortex, spinal cord network and muscles, we developed a model for neural control of goal-directed reaching movements that simulates the entire pathway from the motor cortex through spinal cord circuits to the muscles controlling arm movements. In this model, the arm consists of two joints (shoulder and elbow), whose movements are actuated by six muscles (4 single-joint and 2 double-joint flexors and extensors). The muscles provide afferent feedback to the spinal cord circuits. Cortical neurons are defined as cortical "controllers" that solve an inverse problem based on a proposed straight-line trajectory to a target position and a predefined bell-shaped velocity profile. Thus, the controller generates a motor program that produces a task-specific activation of low-level spinal circuits that in turn induce the muscle activation realizing the intended reaching movement. Using the model, we describe the mechanisms of correlation between cortical and motoneuronal activities and movement direction and other movement parameters. We show that the directional modulation of neuronal activity in the motor cortex and the spinal cord may result from direction-specific dynamics of muscle lengths. Our model suggests that directional modulation first emerges at the level of muscle forces, augments at the motoneuron level, and further increases at the level of the motor cortex due to the dependence of frictional forces in the joints, contractility of the muscles and afferent feedback on muscle lengths and/or velocities.

[Development and Validation of a Three-Dimensional Finite Element Model of Inferior Cervical Spinal Segments C(4-7) for a Healthy Person].

PubMed

Deng, Zhen; Wang, Huihao; Niu, Wenxin; Lan, Tianying; Wang, Kuan; Zhan, Hongsheng

2016-08-01

This study aims to develop and validate a three-dimensional finite element model of inferior cervical spinal segments C4-7of a healthy volunteer,and to provide a computational platform for investigating the biomechanical mechanism of treating cervical vertebra disease with Traditional Chinese Traumotology Manipulation(TCTM).A series of computed tomography(CT)images of C4-7segments were processed to establish the finite element model using softwares Mimics 17.0,Geromagic12.0,and Abaqus 6.13.A reference point(RP)was created on the endplate of C4 and coupled with all nodes of C4.All loads(±0.5,±1,±1.5and±2Nm)were added to the RP for the six simulations(flexion,extension,lateral bending and axial rotation).Then,the range of motion of each segment was calculated and compared with experimental measurements of in vitro studies.On the other hand,1Nm moment was loaded on the model to observe the main stress regions of the model in different status.We successfully established a detail model of inferior cervical spinal segments C4-7of a healthy volunteer with 591 459 elements and 121 446 nodes which contains the structure of the vertebra,intervertebral discs,ligaments and facet joints.The model showed an accordance result after the comparison with the in vitro studies in the six simulations.Moreover,the main stress region occurred on the model could reflect the main stress distribution of normal human cervical spine.The model is accurate and realistic which is consistent with the biomechanical properties of the cervical spine.The model can be used to explore the biomechanical mechanism of treating cervical vertebra disease with TCTM.

Vertebral osteoporosis: perfused animal cadaver model for testing new vertebroplastic agents.

PubMed

Hoell, Thomas; Huschak, Gerald; Beier, Andre; Holzhausen, Hans-Juergen; Meisel, Hans-Joerg; Emmrich, Frank

2010-12-01

Experimental study. It was aimed to establish a cadaver model to imitate osteoporotic perfused vertebral bone and to allow for transpedicular transfer of bone cement and various new materials into vertebrae. The model was perfused to simulate vertebroplasty in the presence of transvertebral blood flow. The injection of bone cement into vertebrae bears the risk of irreversible discharge of material into the venous system of the spinal canal. The bovine cadaver model studied allows visual studies of material distribution in a vertebral bone, the potential spill-out of material, and quantification of washout and disintegration phenomena. Thoracic and lumbar vertebrae from 1-year-old calves were cut transversally into 5 mm slices, macerated, and decalcified. The softened bone slices were compressed between 2 transparent plastic discs. A standard vertebroplasty cannula (outer diameter 3.5 mm, inner diameter 2.5 mm) was inserted into the vertebral body via the pedicle to transfer the different vertebroplasty materials. Arterial blood flow was simulated by means of liquid irrigation via 2 needles in the ventral part of the vertebral body slice. Metal powder was mixed with the solution to indicate the blood flow in the bone. The model was evaluated with the vertebroplasty cement polymethylmethacrylate. The model permitted visualization of the insertion and distribution of vertebroplasty materials. Liquid bone cement was effused into the spinal canal as in the clinical situation. Higher modulus cement acted in the same way as in clinical vertebroplasty. Rigid vertebroplasty agents led to trabecular fractures and stable mechanical interactions with the bone and eventually moved dorsal bone fragments into the spinal canal. Sedimentation of the metal powder indicated regions of perfusion. The model simulated the clinical behavior of liquid and higher modulus vertebroplasty agents in the presence of blood flow. It enabled safe ex vivo testing of the mechanical and physical properties of alternative vertebroplasty materials under flow conditions.

Diagnostic accuracy of evoked potentials for functional impairment after contusive spinal cord injury in adult rats.

PubMed

Thirumala, Parthasarathy; Zhou, James; Krishnan, Rohan; Manem, Nihita; Umredkar, Shreya; Hamilton, D K; Balzer, Jeffrey R; Oudega, Martin

2016-03-01

Iatrogenic spinal cord injury (SCI) is a cause of potentially debilitating post-operative neurologic complications. Currently, intra-operative neurophysiological monitoring (IONM) via somatosensory evoked potentials and motor-evoked potentials is used to detect and prevent impending SCI. However, no empirically validated interventions exist to halt the progression of iatrogenic SCI once it is detected. This is in part due to the lack of a suitable translational model that mimics the circumstances surrounding iatrogenic SCI detected via IONM. Here, we evaluate a model of simulated contusive iatrogenic SCI detected via IONM in adult female Sprague-Dawley rats. We show that transient losses of somatosensory evoked potentials responses are 88.24% sensitive (95% confidence interval [CI] 63.53-98.20) and 80% specific (95% CI 51.91-95.43) for significant functional impairment following simulated iatrogenic SCI. Similarly, we show that transient losses in motor-evoked potentials responses are 70.83% sensitive (95% CI 48.91-87.33) and 100% specific (95% CI 62.91-100.00) for significant functional impairment following simulated iatrogenic SCI. These results indicate that our model is a suitable replica of the circumstances surrounding clinical iatrogenic SCI. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mechanical Design and Analysis of a Unilateral Cervical Spinal Cord Contusion Injury Model in Non-Human Primates

PubMed Central

Salegio, Ernesto A.; Camisa, William; Tam, Horace; Beattie, Michael S.; Bresnahan, Jacqueline C.

2016-01-01

Abstract Non-human primate (NHP) models of spinal cord injury better reflect human injury and provide a better foundation to evaluate potential treatments and functional outcomes. We combined finite element (FE) and surrogate models with impact data derived from in vivo experiments to define the impact mechanics needed to generate a moderate severity unilateral cervical contusion injury in NHPs (Macaca mulatta). Three independent variables (impactor displacement, alignment, and pre-load) were examined to determine their effects on tissue level stresses and strains. Mechanical measures of peak force, peak displacement, peak energy, and tissue stiffness were analyzed as potential determinants of injury severity. Data generated from FE simulations predicted a lateral shift of the spinal cord at high levels of compression (>64%) during impact. Submillimeter changes in mediolateral impactor position over the midline increased peak impact forces (>50%). Surrogate cords established a 0.5 N pre-load protocol for positioning the impactor tip onto the dural surface to define a consistent dorsoventral baseline position before impact, which corresponded with cerebrospinal fluid displacement and entrapment of the spinal cord against the vertebral canal. Based on our simulations, impactor alignment and pre-load were strong contributors to the variable mechanical and functional outcomes observed in in vivo experiments. Peak displacement of 4 mm after a 0.5N pre-load aligned 0.5–1.0 mm over the midline should result in a moderate severity injury; however, the observed peak force and calculated peak energy and tissue stiffness are required to properly characterize the severity and variability of in vivo NHP contusion injuries. PMID:26670940

Speed of spinal vs general anaesthesia for category-1 caesarean section: a simulation and clinical observation-based study.

PubMed

Kathirgamanathan, A; Douglas, M J; Tyler, J; Saran, S; Gunka, V; Preston, R; Kliffer, P

2013-07-01

Controversy exists as to whether effective spinal anaesthesia can be achieved as quickly as general anaesthesia for a category-1 caesarean section. Sixteen consultants and three fellows in obstetric anaesthesia were timed performing spinal and general anaesthesia for category-1 caesarean section on a simulator. The simulation time commenced upon entry of the anaesthetist into the operating theatre and finished for the spinal anaesthetic at the end of intrathecal injection and for the general anaesthetic when the anaesthetist was happy for surgery to start. In the second clinical part of the study, the time from intrathecal administration to 'adequate surgical anaesthesia' (defined as adequate for start of a category-1 caesarean section) was estimated in 100 elective (category-4) caesarean sections. The median (IQR [range]) times (min:s) for spinal procedure, onset of spinal block and general anaesthesia were 2:56 (2:32-3:32 [1:22-3:50]), 5:56 (4:23-7:39 [2:9-13:32]) and 1:56 (1:39-2:9 [1:13-3:12]), respectively. The limiting factor in urgent spinal anaesthesia is the unpredictable time needed for adequate surgical block to develop. Anaesthesia © 2013 The Association of Anaesthetists of Great Britain and Ireland.

Visualizing the spinal neuronal dynamics of locomotion

NASA Astrophysics Data System (ADS)

Subramanian, Kalpathi R.; Bashor, D. P.; Miller, M. T.; Foster, J. A.

2004-06-01

Modern imaging and simulation techniques have enhanced system-level understanding of neural function. In this article, we present an application of interactive visualization to understanding neuronal dynamics causing locomotion of a single hip joint, based on pattern generator output of the spinal cord. Our earlier work visualized cell-level responses of multiple neuronal populations. However, the spatial relationships were abstract, making communication with colleagues difficult. We propose two approaches to overcome this: (1) building a 3D anatomical model of the spinal cord with neurons distributed inside, animated by the simulation and (2) adding limb movements predicted by neuronal activity. The new system was tested using a cat walking central pattern generator driving a pair of opposed spinal motoneuron pools. Output of opposing motoneuron pools was combined into a single metric, called "Net Neural Drive", which generated angular limb movement in proportion to its magnitude. Net neural drive constitutes a new description of limb movement control. The combination of spatial and temporal information in the visualizations elegantly conveys the neural activity of the output elements (motoneurons), as well as the resulting movement. The new system encompasses five biological levels of organization from ion channels to observed behavior. The system is easily scalable, and provides an efficient interactive platform for rapid hypothesis testing.

[Team training and assessment in mixed reality-based simulated operating room : Current state of research in the field of simulation in spine surgery exemplified by the ATMEOS project].

PubMed

Stefan, P; Pfandler, M; Wucherer, P; Habert, S; Fürmetz, J; Weidert, S; Euler, E; Eck, U; Lazarovici, M; Weigl, M; Navab, N

2018-04-01

Surgical simulators are being increasingly used as an attractive alternative to clinical training in addition to conventional animal models and human specimens. Typically, surgical simulation technology is designed for the purpose of teaching technical surgical skills (so-called task trainers). Simulator training in surgery is therefore in general limited to the individual training of the surgeon and disregards the participation of the rest of the surgical team. The objective of the project Assessment and Training of Medical Experts based on Objective Standards (ATMEOS) is to develop an immersive simulated operating room environment that enables the training and assessment of multidisciplinary surgical teams under various conditions. Using a mixed reality approach, a synthetic patient model, real surgical instruments and radiation-free virtual X‑ray imaging are combined into a simulation of spinal surgery. In previous research studies, the concept was evaluated in terms of realism, plausibility and immersiveness. In the current research, assessment measurements for technical and non-technical skills are developed and evaluated. The aim is to observe multidisciplinary surgical teams in the simulated operating room during minimally invasive spinal surgery and objectively assess the performance of the individual team members and the entire team. Moreover, the effectiveness of training methods and surgical techniques or success critical factors, e. g. management of crisis situations, can be captured and objectively assessed in the controlled environment.

Comparison of in vivo and ex vivo viscoelastic behavior of the spinal cord.

PubMed

Ramo, Nicole L; Shetye, Snehal S; Streijger, Femke; Lee, Jae H T; Troyer, Kevin L; Kwon, Brian K; Cripton, Peter; Puttlitz, Christian M

2018-03-01

Despite efforts to simulate the in vivo environment, post-mortem degradation and lack of blood perfusion complicate the use of ex vivo derived material models in computational studies of spinal cord injury. In order to quantify the mechanical changes that manifest ex vivo, the viscoelastic behavior of in vivo and ex vivo porcine spinal cord samples were compared. Stress-relaxation data from each condition were fit to a non-linear viscoelastic model using a novel characterization technique called the direct fit method. To validate the presented material models, the parameters obtained for each condition were used to predict the respective dynamic cyclic response. Both ex vivo and in vivo samples displayed non-linear viscoelastic behavior with a significant increase in relaxation with applied strain. However, at all three strain magnitudes compared, ex vivo samples experienced a higher stress and greater relaxation than in vivo samples. Significant differences between model parameters also showed distinct relaxation behaviors, especially in non-linear relaxation modulus components associated with the short-term response (0.1-1 s). The results of this study underscore the necessity of utilizing material models developed from in vivo experimental data for studies of spinal cord injury, where the time-dependent properties are critical. The ability of each material model to accurately predict the dynamic cyclic response validates the presented methodology and supports the use of the in vivo model in future high-resolution finite element modeling efforts. Neural tissues (such as the brain and spinal cord) display time-dependent, or viscoelastic, mechanical behavior making it difficult to model how they respond to various loading conditions, including injury. Methods that aim to characterize the behavior of the spinal cord almost exclusively use ex vivo cadaveric or animal samples, despite evidence that time after death affects the behavior compared to that in a living animal (in vivo response). Therefore, this study directly compared the mechanical response of ex vivo and in vivo samples to quantify these differences for the first time. This will allow researchers to draw more accurate conclusions about spinal cord injuries based on ex vivo data (which are easier to obtain) and emphasizes the importance of future in vivo experimental animal work. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Interface Stability Influences Torso Muscle Recruitment and Spinal Load During Pushing Tasks

PubMed Central

LEE, P. J.; GRANATA, K. P.

2006-01-01

Handle or interface design can influence torso muscle recruitment and spinal load during pushing tasks. The objective of the study was to provide insight into the role of interface stability with regard to torso muscle recruitment and biomechanical loads on the spine. Fourteen subjects generated voluntary isometric trunk flexion force against a rigid interface and similar flexion exertions against an unstable interface, which simulated handle design in a cart pushing task. Normalized electromyographic (EMG) activity in the rectus abdominus, external oblique and internal oblique muscles increased with exertion effort. When using the unstable interface, EMG activity in the internal and external oblique muscle groups was greater than when using the rigid interface. Results agreed with trends from a biomechanical model implemented to predict the muscle activation necessary to generate isometric pushing forces and maintain spinal stability when using the two different interface designs. The co-contraction contributed to increased spinal load when using the unstable interface. It was concluded that handle or interface design and stability may influence spinal load and associated risk of musculoskeletal injury during manual materials tasks that involve pushing exertions. PMID:16540437

Wheelchair pushing and turning: lumbar spine and shoulder loads and recommended limits.

PubMed

Weston, Eric B; Khan, Safdar N; Marras, William S

2017-12-01

The objective of this study was to determine how simulated manual wheelchair pushing influences biomechanical loading to the lumbar spine and shoulders. Sixty-two subjects performed simulated wheelchair pushing and turning in a laboratory. An electromyography-assisted biomechanical model was used to estimate spinal loads. Moments at the shoulder joint, external hand forces and net turning torque were also assessed. Multiple linear regression techniques were employed to develop biomechanically based wheelchair pushing guidelines relating resultant hand force or net torque to spinal load. Male subjects experienced significantly greater spinal loading (p < 0.01), and spine loads were also increased for wheelchair turning compared to straight wheelchair pushing (p < 0.001). Biomechanically determined maximum acceptable resultant hand forces were 17-18% lower than psychophysically determined limits. We conclude that manual wheelchair pushing and turning can pose biomechanical risk to the lumbar spine and shoulders. Psychophysically determined maximum acceptable push forces do not appear to be protective enough of this biomechanical risk. Practitioner Summary: This laboratory study investigated biomechanical risk to the low back and shoulders during simulated wheelchair pushing. Manual wheelchair pushing posed biomechanical risk to the lumbar spine (in compression and A/P shear) and to the shoulders. Biomechanically determined wheelchair pushing thresholds are presented and are more protective than the closest psychophysically determined equivalents.

In Vivo Rodent Models of Skeletal Muscle Adaptation to Decreased Use.

PubMed

Cho, Su Han; Kim, Jang Hoe; Song, Wook

2016-03-01

Skeletal muscle possesses plasticity and adaptability to external and internal physiological changes. Due to these characteristics, skeletal muscle shows dramatic changes depending on its response to stimuli such as physical activity, nutritional changes, disease status, and environmental changes. Modulation of the rate of protein synthesis/degradation plays an important role in atrophic responses. The purpose of this review is to describe different features of skeletal muscle adaptation with various models of deceased use. In this review, four models were addressed: immobilization, spinal cord transection, hindlimb unloading, and aging. Immobilization is a form of decreased use in which skeletal muscle shows electrical activity, tension development, and motion. These results differ by muscle group. Spinal cord transection was selected to simulate spinal cord injury. Similar to the immobilization model, dramatic atrophy occurs in addition to fiber type conversion in this model. Despite the fact that electromyography shows unremarkable changes in muscle after hindlimb unloading, decreased muscle mass and contractile force are observed. Lastly, aging significantly decreases the numbers of muscle fibers and motor units. Skeletal muscle responses to decreased use include decreased strength, decreased fiber numbers, and fiber type transformation. These four models demonstrated different changes in the skeletal muscle. This review elucidates the different skeletal muscle adaptations in these four decreased use animal models and encourages further studies.

Growth of adult spinal cord in knifefish: Development and parametrization of a distributed model.

PubMed

Ilieş, Iulian; Sipahi, Rifat; Zupanc, Günther K H

2018-01-21

The study of indeterminate-growing organisms such as teleost fish presents a unique opportunity for improving our understanding of central nervous tissue growth during adulthood. Integrating the existing experimental data associated with this process into a theoretical framework through mathematical or computational modeling provides further research avenues through sensitivity analysis and optimization. While this type of approach has been used extensively in investigations of tumor growth, wound healing, and bone regeneration, the development of nervous tissue has been rarely studied within a modeling framework. To address this gap, the present work introduces a distributed model of spinal cord growth in the knifefish Apteronotus leptorhynchus, an established teleostean model of adult growth in the central nervous system. The proposed model incorporates two mechanisms, cell proliferation by active stem/progenitor cells and cell drift due to population pressure, both of which are subject to global constraints. A coupled reaction-diffusion equation approach was adopted to represent the densities of actively-proliferating and non-proliferating cells along the longitudinal axis of the spinal cord. Computer simulations using this model yielded biologically-feasible growth trajectories. Subsequent comparisons with whole-organism growth curves allowed the estimation of previously-unknown parameters, such as relative growth rates. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Computational, Tissue-Realistic Model of Pressure Ulcer Formation in Individuals with Spinal Cord Injury.

PubMed

Ziraldo, Cordelia; Solovyev, Alexey; Allegretti, Ana; Krishnan, Shilpa; Henzel, M Kristi; Sowa, Gwendolyn A; Brienza, David; An, Gary; Mi, Qi; Vodovotz, Yoram

2015-06-01

People with spinal cord injury (SCI) are predisposed to pressure ulcers (PU). PU remain a significant burden in cost of care and quality of life despite improved mechanistic understanding and advanced interventions. An agent-based model (ABM) of ischemia/reperfusion-induced inflammation and PU (the PUABM) was created, calibrated to serial images of post-SCI PU, and used to investigate potential treatments in silico. Tissue-level features of the PUABM recapitulated visual patterns of ulcer formation in individuals with SCI. These morphological features, along with simulated cell counts and mediator concentrations, suggested that the influence of inflammatory dynamics caused simulations to be committed to "better" vs. "worse" outcomes by 4 days of simulated time and prior to ulcer formation. Sensitivity analysis of model parameters suggested that increasing oxygen availability would reduce PU incidence. Using the PUABM, in silico trials of anti-inflammatory treatments such as corticosteroids and a neutralizing antibody targeted at Damage-Associated Molecular Pattern molecules (DAMPs) suggested that, at best, early application at a sufficiently high dose could attenuate local inflammation and reduce pressure-associated tissue damage, but could not reduce PU incidence. The PUABM thus shows promise as an adjunct for mechanistic understanding, diagnosis, and design of therapies in the setting of PU.

A Computational, Tissue-Realistic Model of Pressure Ulcer Formation in Individuals with Spinal Cord Injury

PubMed Central

Ziraldo, Cordelia; Solovyev, Alexey; Allegretti, Ana; Krishnan, Shilpa; Henzel, M. Kristi; Sowa, Gwendolyn A.; Brienza, David; An, Gary; Mi, Qi; Vodovotz, Yoram

2015-01-01

People with spinal cord injury (SCI) are predisposed to pressure ulcers (PU). PU remain a significant burden in cost of care and quality of life despite improved mechanistic understanding and advanced interventions. An agent-based model (ABM) of ischemia/reperfusion-induced inflammation and PU (the PUABM) was created, calibrated to serial images of post-SCI PU, and used to investigate potential treatments in silico. Tissue-level features of the PUABM recapitulated visual patterns of ulcer formation in individuals with SCI. These morphological features, along with simulated cell counts and mediator concentrations, suggested that the influence of inflammatory dynamics caused simulations to be committed to “better” vs. “worse” outcomes by 4 days of simulated time and prior to ulcer formation. Sensitivity analysis of model parameters suggested that increasing oxygen availability would reduce PU incidence. Using the PUABM, in silico trials of anti-inflammatory treatments such as corticosteroids and a neutralizing antibody targeted at Damage-Associated Molecular Pattern molecules (DAMPs) suggested that, at best, early application at a sufficiently high dose could attenuate local inflammation and reduce pressure-associated tissue damage, but could not reduce PU incidence. The PUABM thus shows promise as an adjunct for mechanistic understanding, diagnosis, and design of therapies in the setting of PU. PMID:26111346

In vivo distribution of spinal intervertebral stiffness based on clinical flexibility tests.

PubMed

Lafon, Yoann; Lafage, Virginie; Steib, Jean-Paul; Dubousset, Jean; Skalli, Wafa

2010-01-15

A numerical study was conducted to identify the intervertebral stiffness of scoliotic spines from spinal flexibility tests. To study the intervertebral 3-dimensional (3D) stiffness distribution along scoliotic spine. Few methods have been reported in literature to quantify the in vivo 3D intervertebral stiffness of the scoliotic spine. Based on the simulation of flexibility tests, these methods were operator-dependent and could yield to clinically irrelevant stiffnesses. This study included 30 patients surgically treated for severe idiopathic scoliosis. A previously validated trunk model, with patient-specific geometry, was used to simulate bending tests according to the in vivo displacements of T1 and L5 measured from bending test radiographs. Differences between in vivo and virtual spinal behaviors during bending tests (left and right) were computed in terms of vertebral rotations and translation. An automated method, driven by a priori knowledge, identified intervertebral stiffnesses in order to reproduce the in vivo spinal behavior. Because of the identification of intervertebral stiffnesses, differences between in vivo and virtual spinal displacements were drastically reduced (95% of the differences less than +/-3 mm for vertebral translation). Intervertebral stiffness distribution after identification was analyzed. On convex side test, the intervertebral stiffness of the compensatory curves increased in most cases, whereas the major curve became more flexible. Stiffness singularities were found in junctional zones: these specific levels were predominantly flexible, both in torsion and in lateral bending. The identification of in vivo intervertebral stiffness may improve our understanding of scoliotic spine and the relevance of patient-specific methods for surgical planning.

Physiological changes in fast and slow muscle with simulated weightlessness

NASA Technical Reports Server (NTRS)

Dettbarn, W. D.; Misulis, K. E.

1984-01-01

A rat hindlimb suspension model of simulated weightlessness was used to examine the physiological characteristics of skeletal muscle. The physiological sequelae of hindlimb suspension were compared to those of spinal cord section, denervation by sciatic nerve crush, and control. Muscle examined were the predominantly slow (Type 1) soleus (SOL) and the predominantly fast (Type 2) extensor digitorum longus (EDL). Two procedures which alter motor unit activity, hindlimb suspension and spinal cord section, produce changes in characteristics of skeletal muscles that are dependent upon fiber type. The SOL develops characteristics more representative of a fast muscle, including smaller Type 1 fiber proportion and higher AChE activity. The EDL, which is already predominantly fast, loses most of its few Type 1 fibers, thus also becoming faster. These data are in agreement with the studies in which rats experienced actual weightlessness.

Simulated microgravity facilitates cell migration and neuroprotection after bone marrow stromal cell transplantation in spinal cord injury

PubMed Central

2013-01-01

Introduction Recently, cell-based therapy has gained significant attention for the treatment of central nervous system diseases. Although bone marrow stromal cells (BMSCs) are considered to have good engraftment potential, challenges due to in vitro culturing, such as a decline in their functional potency, have been reported. Here, we investigated the efficacy of rat BMSCs (rBMSCs) cultured under simulated microgravity conditions, for transplantation into a rat model of spinal cord injury (SCI). Methods rBMSCs were cultured under two different conditions: standard gravity (1G) and simulated microgravity attained by using the 3D-clinostat. After 7 days of culture, the rBMSCs were analyzed morphologically, with RT-PCR and immunostaining, and were used for grafting. Adult rats were used for constructing SCI models by using a weight-dropping method and were grouped into three experimental groups for comparison. rBMSCs cultured under 1 g and simulated microgravity were transplanted intravenously immediately after SCI. We evaluated the hindlimb functional improvement for 3 weeks. Tissue repair after SCI was examined by calculating the cavity area ratio and immunohistochemistry. Results rBMSCs cultured under simulated microgravity expressed Oct-4 and CXCR4, in contrast to those cultured under 1 g conditions. Therefore, rBMSCs cultured under simulated microgravity were considered to be in an undifferentiated state and thus to possess high migration ability. After transplantation, grafted rBMSCs cultured under microgravity exhibited greater survival at the periphery of the lesion, and the motor functions of the rats that received these grafts improved significantly compared with the rats that received rBMSCs cultured in 1 g. In addition, rBMSCs cultured under microgravity were thought to have greater trophic effects on reestablishment and survival of host spinal neural tissues because cavity formations were reduced, and apoptosis-inhibiting factor expression was high at the periphery of the SCI lesion. Conclusions Here we show that transplantation of rBMSCs cultured under simulated microgravity facilitates functional recovery from SCI rather than those cultured under 1 g conditions. PMID:23548163

The application of operations research methodologies to the delivery of care model for traumatic spinal cord injury: the access to care and timing project.

PubMed

Noonan, Vanessa K; Soril, Lesley; Atkins, Derek; Lewis, Rachel; Santos, Argelio; Fehlings, Michael G; Burns, Anthony S; Singh, Anoushka; Dvorak, Marcel F

2012-09-01

The long-term impact of spinal cord injury (SCI) on the health care system imposes a need for greater efficiency in the use of resources and the management of care. The Access to Care and Timing (ACT) project was developed to model the health care delivery system in Canada for patients with traumatic SCI. Techniques from Operations Research, such as simulation modeling, were used to predict the impact of best practices and policy initiatives on outcomes related to both the system and patients. These methods have been used to solve similar problems in business and engineering and may offer a unique solution to the complexities encountered in SCI care delivery. Findings from various simulated scenarios, from the patients' point of injury to community re-integration, can be used to inform decisions on optimizing practice across the care continuum. This article describes specifically the methodology and implications of producing such simulations for the care of traumatic SCI in Canada. Future publications will report on specific practices pertaining to the access to specialized services and the timing of interventions evaluated using the ACT model. Results from this type of research will provide the evidence required to support clinical decision making, inform standards of care, and provide an opportunity to engage policymakers.

The Application of Operations Research Methodologies to the Delivery of Care Model for Traumatic Spinal Cord Injury: The Access to Care and Timing Project

PubMed Central

Noonan, Vanessa K.; Soril, Lesley; Atkins, Derek; Lewis, Rachel; Santos, Argelio; Fehlings, Michael G.; Burns, Anthony S.; Singh, Anoushka

2012-01-01

Abstract The long-term impact of spinal cord injury (SCI) on the health care system imposes a need for greater efficiency in the use of resources and the management of care. The Access to Care and Timing (ACT) project was developed to model the health care delivery system in Canada for patients with traumatic SCI. Techniques from Operations Research, such as simulation modeling, were used to predict the impact of best practices and policy initiatives on outcomes related to both the system and patients. These methods have been used to solve similar problems in business and engineering and may offer a unique solution to the complexities encountered in SCI care delivery. Findings from various simulated scenarios, from the patients' point of injury to community re-integration, can be used to inform decisions on optimizing practice across the care continuum. This article describes specifically the methodology and implications of producing such simulations for the care of traumatic SCI in Canada. Future publications will report on specific practices pertaining to the access to specialized services and the timing of interventions evaluated using the ACT model. Results from this type of research will provide the evidence required to support clinical decision making, inform standards of care, and provide an opportunity to engage policymakers. PMID:22800432

Optimizing Filter-Probe Diffusion Weighting in the Rat Spinal Cord for Human Translation

PubMed Central

Budde, Matthew D.; Skinner, Nathan P.; Muftuler, L. Tugan; Schmit, Brian D.; Kurpad, Shekar N.

2017-01-01

Diffusion tensor imaging (DTI) is a promising biomarker of spinal cord injury (SCI). In the acute aftermath, DTI in SCI animal models consistently demonstrates high sensitivity and prognostic performance, yet translation of DTI to acute human SCI has been limited. In addition to technical challenges, interpretation of the resulting metrics is ambiguous, with contributions in the acute setting from both axonal injury and edema. Novel diffusion MRI acquisition strategies such as double diffusion encoding (DDE) have recently enabled detection of features not available with DTI or similar methods. In this work, we perform a systematic optimization of DDE using simulations and an in vivo rat model of SCI and subsequently implement the protocol to the healthy human spinal cord. First, two complementary DDE approaches were evaluated using an orientationally invariant or a filter-probe diffusion encoding approach. While the two methods were similar in their ability to detect acute SCI, the filter-probe DDE approach had greater predictive power for functional outcomes. Next, the filter-probe DDE was compared to an analogous single diffusion encoding (SDE) approach, with the results indicating that in the spinal cord, SDE provides similar contrast with improved signal to noise. In the SCI rat model, the filter-probe SDE scheme was coupled with a reduced field of view (rFOV) excitation, and the results demonstrate high quality maps of the spinal cord without contamination from edema and cerebrospinal fluid, thereby providing high sensitivity to injury severity. The optimized protocol was demonstrated in the healthy human spinal cord using the commercially-available diffusion MRI sequence with modifications only to the diffusion encoding directions. Maps of axial diffusivity devoid of CSF partial volume effects were obtained in a clinically feasible imaging time with a straightforward analysis and variability comparable to axial diffusivity derived from DTI. Overall, the results and optimizations describe a protocol that mitigates several difficulties with DTI of the spinal cord. Detection of acute axonal damage in the injured or diseased spinal cord will benefit the optimized filter-probe diffusion MRI protocol outlined here. PMID:29311786

Biomechanical study of anterior spinal instrumentation configurations

PubMed Central

Cloutier, Luc P.; Grimard, Guy

2007-01-01

The biomechanical impact of the surgical instrumentation configuration for spine surgery is hard to evaluate by the surgeons in pre-operative situation. This study was performed to evaluate different configurations of the anterior instrumentation of the spine, with simulated post-operative conditions, to recommend configurations to the surgeons. Four biomechanical parameters of the anterior instrumentation with simulated post-operative conditions have been studied. They were the screw diameter (5.5–7.5 mm) and its angle (0°–22.5°), the bone grip of the screw (mono–bi cortical) and the amount of instrumented levels (5–8). Eight configurations were tested using an experimental plan with instrumented synthetic spinal models. A follower load was applied and the models were loaded in flexion, torsion and lateral bending. At 5 Nm, average final stiffness was greater in flexion (0.92 Nm/°) than in lateral bending (0.56 Nm/°) and than in torsion (0.26 Nm/°). The screw angle was the parameter influencing the most the final stiffness and the coupling behaviors. It has a significant effect (p ≤ 0.05) on increasing the final stiffness for a 22.5° screw angle in flexion and for a coronal screw angle (0°) in lateral bending. The bi-cortical bone grip of the screw significantly increased the initial stiffness in flexion and lateral bending. Mathematical models representing the behavior of an instrumented spinal model have been used to identify optimal instrumentation configurations. A variation of the angle of the screw from 22.5° to 0° gave a global final stiffness diminution of 13% and a global coupling diminution of 40%. The screw angle was the most important parameter affecting the stiffness and the coupling of the instrumented spine with simulated post-operative conditions. Information about the effect of four different biomechanical parameters will be helpful in preoperative situations to guide surgeons in their clinical choices. PMID:17205240

Electrode contact configuration and energy consumption in spinal cord stimulation.

PubMed

de Vos, Cecile C; Hilgerink, Marjolein P; Buschman, Hendrik P J; Holsheimer, Jan

2009-12-01

To test the hypothesis that in spinal cord stimulation, an increase in the number of cathodes increases the energy per pulse, contrary to an increase in the number of anodes, which decreases energy consumption per pulse. Patients with an Itrel III (7425; Medtronic, Inc., Minneapolis, MN) implantable pulse generator and a Pisces-Quad (3487A; Medtronic, Inc.) implantable quadripolar lead were selected for this study. A set of 7 standard contact configurations was used for each patient. Resistor network models mimicking these configurations were constructed. The University of Twente's Spinal Cord Stimulation software was used to simulate the effect of these contact configurations on large spinal nerve fibers. To allow a comparison of the measured and modeled energy per pulse, all values were normalized. Both the empirical and the modeling results showed an increase in energy consumption with an increasing number of cathodes. Although the patient data with 1 and 2 cathodes did not differ significantly, energy consumption was significantly higher when 3 cathodes were used instead of 1 or 2 cathodes. The average energy consumption was significantly higher when bipolar stimulation was used instead of monopolar cathodal stimulation. An increasing number of anodes caused a decrease in energy consumption. When the paresthesia area can be covered with several configurations, it will be beneficial for the patient to program a configuration with 1 cathode and either no or multiple anodes.

A whole-body mathematical model for intracranial pressure dynamics.

PubMed

Lakin, William D; Stevens, Scott A; Tranmer, Bruce I; Penar, Paul L

2003-04-01

Most attempts to study intracranial pressure using lumped-parameter models have adopted the classical "Kellie-Monro Doctrine," which considers the intracranial space to be a closed system that is confined within the nearly-rigid skull, conserves mass, and has equal inflow and outflow. The present work revokes this Doctrine and develops a mathematical model for the dynamics of intracranial pressures, volumes, and flows that embeds the intracranial system in extensive whole-body physiology. The new model consistently introduces compartments representing the tissues and vasculature of the extradural portions of the body, including both the thoracic region and the lower extremities. In addition to vascular connections, a spinal-subarachnoid cerebrospinal fluid (CSF) compartment bridges intracranial and extracranial physiology allowing explict buffering of intracranial pressure fluctuations by the spinal theca. The model contains cerebrovascular autoregulation, regulation of systemic vascular pressures by the sympathetic nervous system, regulation of CSF production in the choroid plexus, a lymphatic system, colloid osmotic pressure effects, and realistic descriptions of cardiac output. To validate the model in situations involving normal physiology, the model's response to a realistic pulsatile cardiac output is examined. A well-known experimentally-derived intracranial pressure-volume relationship is recovered by using the model to simulate CSF infusion tests, and the effect on cerebral blood flow of a change in body position is also examined. Cardiac arrest and hemorrhagic shock are simulated to demonstrate the predictive capabilities of the model in pathological conditions.

Design and performance test of NIRS-based spinal cord lesion detector

NASA Astrophysics Data System (ADS)

Li, Nanxi; Li, Ting

2018-02-01

Spinal cord lesions can cause a series of severe complications, which can even lead to paralysis with high mortality. However, the traditional diagnosis of spinal cord lesion relies on complicated imaging modalities and other invasive and dangerous methods. Here, we have designed a small monitor based on NIRS technology for noninvasive monitoring for spinal cord lesions. The development of the instrument system includes the design of hardware circuits and the program of software. In terms of hardware, OPT1011 is selected as the light detector, and the appropriate probe distribution structure is selected according to the simulation result of Monte Carlo Simulation. At the same time, the powerful controller is selected as our system's central processing chip for the circuit design, and the data is transmitted by serial port to the host computer for post processing. Finally, we verify the stability and feasibility of the instrument system. It is found that the spinal signal could be obviously detected in the system, which indicates that our monitor based on NIRS technology has the potential to monitor the spinal lesion.

A Low-Cost, Passive Navigation Training System for Image-Guided Spinal Intervention.

PubMed

Lorias-Espinoza, Daniel; Carranza, Vicente González; de León, Fernando Chico-Ponce; Escamirosa, Fernando Pérez; Martinez, Arturo Minor

2016-11-01

Navigation technology is used for training in various medical specialties, not least image-guided spinal interventions. Navigation practice is an important educational component that allows residents to understand how surgical instruments interact with complex anatomy and to learn basic surgical skills such as the tridimensional mental interpretation of bidimensional data. Inexpensive surgical simulators for spinal surgery, however, are lacking. We therefore designed a low-cost spinal surgery simulator (Spine MovDigSys 01) to allow 3-dimensional navigation via 2-dimensional images without altering or limiting the surgeon's natural movement. A training system was developed with an anatomical lumbar model and 2 webcams to passively digitize surgical instruments under MATLAB software control. A proof-of-concept recognition task (vertebral body cannulation) and a pilot test of the system with 12 neuro- and orthopedic surgeons were performed to obtain feedback on the system. Position, orientation, and kinematic variables were determined and the lateral, posteroanterior, and anteroposterior views obtained. The system was tested with a proof-of-concept experimental task. Operator metrics including time of execution (t), intracorporeal length (d), insertion angle (α), average speed (v¯), and acceleration (a) were obtained accurately. These metrics were converted into assessment metrics such as smoothness of operation and linearity of insertion. Results from initial testing are shown and the system advantages and disadvantages described. This low-cost spinal surgery training system digitized the position and orientation of the instruments and allowed image-guided navigation, the generation of metrics, and graphic recording of the instrumental route. Spine MovDigSys 01 is useful for development of basic, noninnate skills and allows the novice apprentice to quickly and economically move beyond the basics. Copyright © 2016 Elsevier Inc. All rights reserved.

Responses of the Acutely Injured Spinal Cord to Vibration that Simulates Transport in Helicopters or Mine-Resistant Ambush-Protected Vehicles.

PubMed

Streijger, Femke; Lee, Jae H T; Manouchehri, Neda; Melnyk, Angela D; Chak, Jason; Tigchelaar, Seth; So, Kitty; Okon, Elena B; Jiang, Shudong; Kinsler, Rachel; Barazanji, Khalid; Cripton, Peter A; Kwon, Brian K

2016-12-15

In the military environment, injured soldiers undergoing medical evacuation via helicopter or mine-resistant ambush-protected vehicle (MRAP) are subjected to vibration and shock inherent to the transport vehicle. We conducted the present study to assess the consequences of such vibration on the acutely injured spinal cord. We used a porcine model of spinal cord injury (SCI). After a T10 contusion-compression injury, animals were subjected to 1) no vibration (n = 7-8), 2) whole body vibration at frequencies and amplitudes simulating helicopter transport (n = 8), or 3) whole body vibration simulating ground transportation in an MRAP ambulance (n = 7). Hindlimb locomotor function (using Porcine Thoracic Injury Behavior Scale [PTIBS]), Eriochrome Cyanine histochemistry and biochemical analysis of inflammatory and neural damage markers were analyzed. Cerebrospinal fluid (CSF) expression levels for monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, IL-8, and glial fibrillary acidic protein (GFAP) were similar between the helicopter or MRAP group and the unvibrated controls. Spared white/gray matter tended to be lower in the MRAP-vibrated animals than in the unvibrated controls, especially rostral to the epicenter. However, spared white/gray matter in the helicopter-vibrated group appeared normal. Although there was a relationship between the extent of sparing and the extent of locomotor recovery, no significant differences were found in PTIBS scores between the groups. In summary, exposures to vibration in the context of ground (MRAP) or aeromedical (helicopter) transportation did not significantly impair functional outcome in our large animal model of SCI. However, MRAP vibration was associated with increased tissue damage around the injury site, warranting caution around exposure to vehicle vibration acutely after SCI.

The Animal Model of Spinal Cord Injury as an Experimental Pain Model

PubMed Central

Nakae, Aya; Nakai, Kunihiro; Yano, Kenji; Hosokawa, Ko; Shibata, Masahiko; Mashimo, Takashi

2011-01-01

Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models. PMID:21436995

Biomechanical effects of fusion levels on the risk of proximal junctional failure and kyphosis in lumbar spinal fusion surgery.

PubMed

Park, Won Man; Choi, Dae Kyung; Kim, Kyungsoo; Kim, Yongjung J; Kim, Yoon Hyuk

2015-12-01

Spinal fusion surgery is a widely used surgical procedure for sagittal realignment. Clinical studies have reported that spinal fusion may cause proximal junctional kyphosis and failure with disc failure, vertebral fracture, and/or failure at the implant-bone interface. However, the biomechanical injury mechanisms of proximal junctional kyphosis and failure remain unclear. A finite element model of the thoracolumbar spine was used. Nine fusion models with pedicle screw systems implanted at the L2-L3, L3-L4, L4-L5, L5-S1, L2-L4, L3-L5, L4-S1, L2-L5, and L3-S1 levels were developed based on the respective surgical protocols. The developed models simulated flexion-extension using hybrid testing protocol. When spinal fusion was performed at more distal levels, particularly at the L5-S1 level, the following biomechanical properties increased during flexion-extension: range of motion, stress on the annulus fibrosus fibers and vertebra at the adjacent motion segment, and the magnitude of axial forces on the pedicle screw at the uppermost instrumented vertebra. The results of this study demonstrate that more distal fusion levels, particularly in spinal fusion including the L5-S1 level, lead to greater increases in the risk of proximal junctional kyphosis and failure, as evidenced by larger ranges of motion, higher stresses on fibers of the annulus fibrosus and vertebra at the adjacent segment, and higher axial forces on the screw at the uppermost instrumented vertebra in flexion-extension. Therefore, fusion levels should be carefully selected to avoid proximal junctional kyphosis and failure. Copyright © 2015 Elsevier Ltd. All rights reserved.

Spinal Cord Stimulation Modulates Gene Expression in the Spinal Cord of an Animal Model of Peripheral Nerve Injury.

PubMed

Tilley, Dana M; Cedeño, David L; Kelley, Courtney A; Benyamin, Ramsin; Vallejo, Ricardo

Previously, we found that application of pulsed radiofrequency to a peripheral nerve injury induces changes in key genes regulating nociception concurrent with alleviation of paw sensitivity in an animal model. In the current study, we evaluated such genes after applying spinal cord stimulation (SCS) therapy. Male Sprague-Dawley rats (n = 6 per group) were randomized into test and control groups. The spared nerve injury model was used to simulate a neuropathic pain state. A 4-contact microelectrode was implanted at the L1 vertebral level and SCS was applied continuously for 72 hours. Mechanical hyperalgesia was tested. Spinal cord tissues were collected and analyzed using real-time polymerase chain reaction to quantify levels of IL1β, GABAbr1, subP, Na/K ATPase, cFos, 5HT3ra, TNFα, Gal, VIP, NpY, IL6, GFAP, ITGAM, and BDNF. Paw withdrawal thresholds significantly decreased in spared nerve injury animals and stimulation attenuated sensitivity within 24 hours (P = 0.049), remaining significant through 72 hours (P = 0.003). Nerve injury caused up-regulation of TNFα, GFAP, ITGAM, and cFOS as well as down-regulation of Na/K ATPase. Spinal cord stimulation therapy modulated the expression of 5HT3ra, cFOS, and GABAbr1. Strong inverse relationships in gene expression relative to the amount of applied current were observed for GABAbr1 (R = -0.65) and Na/K ATPase (R = -0.58), and a positive linear correlations between 5HT3r (R = 0.80) and VIP (R = 0.50) were observed. Continuously applied SCS modulates expression of key genes involved in the regulation of neuronal membrane potential.

Advantages of soft subdural implants for the delivery of electrochemical neuromodulation therapies to the spinal cord

NASA Astrophysics Data System (ADS)

Capogrosso, Marco; Gandar, Jerome; Greiner, Nathan; Moraud, Eduardo Martin; Wenger, Nikolaus; Shkorbatova, Polina; Musienko, Pavel; Minev, Ivan; Lacour, Stephanie; Courtine, Grégoire

2018-04-01

Objective. We recently developed soft neural interfaces enabling the delivery of electrical and chemical stimulation to the spinal cord. These stimulations restored locomotion in animal models of paralysis. Soft interfaces can be placed either below or above the dura mater. Theoretically, the subdural location combines many advantages, including increased selectivity of electrical stimulation, lower stimulation thresholds, and targeted chemical stimulation through local drug delivery. However, these advantages have not been documented, nor have their functional impact been studied in silico or in a relevant animal model of neurological disorders using a multimodal neural interface. Approach. We characterized the recruitment properties of subdural interfaces using a realistic computational model of the rat spinal cord that included explicit representation of the spinal roots. We then validated and complemented computer simulations with electrophysiological experiments in rats. We additionally performed behavioral experiments in rats that received a lateral spinal cord hemisection and were implanted with a soft interface. Main results. In silico and in vivo experiments showed that the subdural location decreased stimulation thresholds compared to the epidural location while retaining high specificity. This feature reduces power consumption and risks of long-term damage in the tissues, thus increasing the clinical safety profile of this approach. The hemisection induced a transient paralysis of the leg ipsilateral to the injury. During this period, the delivery of electrical stimulation restricted to the injured side combined with local chemical modulation enabled coordinated locomotor movements of the paralyzed leg without affecting the non-impaired leg in all tested rats. Electrode properties remained stable over time, while anatomical examinations revealed excellent bio-integration properties. Significance. Soft neural interfaces inserted subdurally provide the opportunity to deliver electrical and chemical neuromodulation therapies using a single, bio-compatible and mechanically compliant device that effectively alleviates locomotor deficits after spinal cord injury.

Optimization of low-level light therapy's illumination parameters for spinal cord injury in a rat model

NASA Astrophysics Data System (ADS)

Shuaib, Ali; Bourisly, Ali

2018-02-01

Spinal cord injury (SCI) can result in complete or partial loss of sensation and motor function due to interruption along the severed axonal tract(s). SCI can result in tetraplegia or paraplegia, which can have prohibitive lifetime medical costs and result in shorter life expectancy. A promising therapeutic technique that is currently in experimental phase and that has the potential to be used to treat SCI is Low-level light therapy (LLLT). Preclinical studies have shown that LLLT has reparative and regenerative capabilities on transected spinal cords, and that LLLT can enhance axonal sprouting in animal models. However, despite the promising effects of LLLT as a therapy for SCI, it remains difficult to compare published results due to the use of a wide range of illumination parameters (i.e. different wavelengths, fluences, beam types, and beam diameter), and due to the lack of a standardized experimental protocol(s). Before any clinical applications of LLLT for SCI treatment, it is crucial to standardize illumination parameters and efficacy of light delivery. Therefore, in this study we aim to evaluate the light fluence distribution on a 3D voxelated SCI rat model with different illumination parameters (wavelengths: 660, 810, and 980 nm; beam types: Gaussian and Flat; and beam diameters: 0.1, 0.2, and 0.3 cm) for LLLT using Monte Carlo simulation. This study provides an efficient approach to guide researchers in optimizing the illumination parameters for LLLT spinal cord injury in an experimental model and will aid in quantitative and qualitative standardization of LLLT-SCI treatment.

A neural circuitry that emphasizes spinal feedback generates diverse behaviours of human locomotion

PubMed Central

Song, Seungmoon; Geyer, Hartmut

2015-01-01

Neural networks along the spinal cord contribute substantially to generating locomotion behaviours in humans and other legged animals. However, the neural circuitry involved in this spinal control remains unclear. We here propose a specific circuitry that emphasizes feedback integration over central pattern generation. The circuitry is based on neurophysiologically plausible muscle-reflex pathways that are organized in 10 spinal modules realizing limb functions essential to legged systems in stance and swing. These modules are combined with a supraspinal control layer that adjusts the desired foot placements and selects the leg that is to transition into swing control during double support. Using physics-based simulation, we test the proposed circuitry in a neuromuscular human model that includes neural transmission delays, musculotendon dynamics and compliant foot–ground contacts. We find that the control network is sufficient to compose steady and transitional 3-D locomotion behaviours including walking and running, acceleration and deceleration, slope and stair negotiation, turning, and deliberate obstacle avoidance. The results suggest feedback integration to be functionally more important than central pattern generation in human locomotion across behaviours. In addition, the proposed control architecture may serve as a guide in the search for the neurophysiological origin and circuitry of spinal control in humans. PMID:25920414

Comparative analysis of international standards for the fatigue testing of posterior spinal fixation systems: the importance of preload in ISO 12189.

PubMed

La Barbera, Luigi; Ottardi, Claudia; Villa, Tomaso

2015-10-01

Preclinical evaluation of the mechanical reliability of fixation devices is a mandatory activity before their introduction into market. There are two standardized protocols for preclinical testing of spinal implants. The American Society for Testing Materials (ASTM) recommends the F1717 standard, which describes a vertebrectomy condition that is relatively simple to implement, whereas the International Organization for Standardization (ISO) suggests the 12189 standard, which describes a more complex physiological anterior support-based setup. Moreover, ASTM F1717 is nowadays well established, whereas ISO 12189 has received little attention: A few studies tried to accurately describe the ISO experimental procedure through numeric models, but these studies totally neglect the recommended precompression step. This study aimed to build up a reliable, validated numeric model capable of describing the stress on the rods of a spinal fixator assembled according to ISO 12189 standard procedure. Such a model would more adequately represent the in vitro testing condition. This study used finite element (FE) simulations and experimental validation testing. An FE model of the ISO setup was built to calculate the stress on the rods. Simulation was validated by comparison with experimental strain gauges measurements. The same fixator has been previously virtually mounted in an L2-L4 FE model of the lumbar spine, and stresses in the rods were calculated when the spine was subjected to physiological forces and moments. The comparison between the FE predictions and experimental measurements is in good agreement, thus confirming the suitability of the FE method to evaluate the stresses in the device. The initial precompression induces a significant extension of the assembled construct. As the applied load increases, the initial extension is gradually compensated, so that at peak load the rods are bent in flexion: The final stress value predicted is thus reduced to about 50%, if compared with the previous model where the precompression was not considered. Neglecting the initial preload due to the assembly of the overall construct according to ISO 12189 standard could lead to an overestimation of the stress on the rods up to 50%. To correctly describe the state of stress on the posterior spinal fixator, tested according to the ISO procedure, it is important to take into account the initial preload due to the assembly of the overall construct. Copyright © 2015 Elsevier Inc. All rights reserved.

A new method to approximate load-displacement relationships of spinal motion segments for patient-specific multi-body models of scoliotic spine.

PubMed

Jalalian, Athena; Tay, Francis E H; Arastehfar, Soheil; Liu, Gabriel

2017-06-01

Load-displacement relationships of spinal motion segments are crucial factors in characterizing the stiffness of scoliotic spine models to mimic the spine responses to loads. Although nonlinear approach to approximation of the relationships can be superior to linear ones, little mention has been made to deriving personalized nonlinear load-displacement relationships in previous studies. A method is developed for nonlinear approximation of load-displacement relationships of spinal motion segments to assist characterizing in vivo the stiffness of spine models. We propose approximation by tangent functions and focus on rotational displacements in lateral direction. The tangent functions are characterized using lateral bending test. A multi-body model was characterized to 18 patients and utilized to simulate four spine positions; right bending, left bending, neutral, and traction. The same was done using linear functions to assess the performance of the proposed tangent function in comparison with the linear function. Root-mean-square error (RMSE) of the displacements estimated by the tangent functions was 44 % smaller than the linear functions. This shows the ability of our tangent function in approximation of the relationships for a range of infinitesimal to large displacements involved in the spine movement to the four positions. In addition, the models based on the tangent functions yielded 67, 55, and 39 % smaller RMSEs of Ferguson angles, locations of vertebrae, and orientations of vertebrae, respectively, implying better estimates of spine responses to loads. Overall, it can be concluded that our method for approximating load-displacement relationships of spinal motion segments can offer good estimates of scoliotic spine stiffness.

Quality of motion considerations in numerical analysis of motion restoring implants of the spine.

PubMed

Bowden, Anton E; Guerin, Heather L; Villarraga, Marta L; Patwardhan, Avinash G; Ochoa, Jorge A

2008-06-01

Motion restoring implants function in a dynamic environment that encompasses the full range of spinal kinematics. Accurate assessment of the in situ performance of these devices using numerical techniques requires model verification and validation against the well-established nonlinear quality of motion of the spine, as opposed to the previous norm of matching kinematic endpoint metrics such as range of motion and intervertebral disc pressure measurements at a single kinematic reference point. Experimental data was obtained during cadaveric testing of nine three-functional spinal unit (L3-S1) lumbar spine segments. Each specimen was tested from 8 Nm of applied flexion moment to 6 Nm of applied extension moment with an applied 400 N compressive follower preload. A nonlinear kinematic curve representing the spinal quality of motion (applied moment versus angular rotation) for the index finite element model was constructed and compared to the kinematic responses of the experimental specimens. The effect of spinal soft tissue structure mechanical behaviors on the fidelity of the model's quality of motion to experimental data was assessed by iteratively modifying the material representations of annulus fibrosus, nucleus pulposus, and ligaments. The present work demonstrated that for this model, the annulus fibrosus played a small role in the nonlinear quality of motion of the model, whereas changes in ligament representations had a large effect, as validated against the full kinematic range of motion. An anisotropic continuum representation of the annulus fibrosus was used, along with nonlinear fabric representations of the ligaments and a hyperelastic representation of the nucleus pulposus. Our results suggest that improvements in current methodologies broadly used in numerical simulations of the lumbar spine are needed to fully describe the highly nonlinear motion of the spine.

[Hardware Implementation of Numerical Simulation Function of Hodgkin-Huxley Model Neurons Action Potential Based on Field Programmable Gate Array].

PubMed

Wang, Jinlong; Lu, Mai; Hu, Yanwen; Chen, Xiaoqiang; Pan, Qiangqiang

2015-12-01

Neuron is the basic unit of the biological neural system. The Hodgkin-Huxley (HH) model is one of the most realistic neuron models on the electrophysiological characteristic description of neuron. Hardware implementation of neuron could provide new research ideas to clinical treatment of spinal cord injury, bionics and artificial intelligence. Based on the HH model neuron and the DSP Builder technology, in the present study, a single HH model neuron hardware implementation was completed in Field Programmable Gate Array (FPGA). The neuron implemented in FPGA was stimulated by different types of current, the action potential response characteristics were analyzed, and the correlation coefficient between numerical simulation result and hardware implementation result were calculated. The results showed that neuronal action potential response of FPGA was highly consistent with numerical simulation result. This work lays the foundation for hardware implementation of neural network.

ASTM F1717 standard for the preclinical evaluation of posterior spinal fixators: can we improve it?

PubMed

La Barbera, Luigi; Galbusera, Fabio; Villa, Tomaso; Costa, Francesco; Wilke, Hans-Joachim

2014-10-01

Preclinical evaluation of spinal implants is a necessary step to ensure their reliability and safety before implantation. The American Society for Testing and Materials reapproved F1717 standard for the assessment of mechanical properties of posterior spinal fixators, which simulates a vertebrectomy model and recommends mimicking vertebral bodies using polyethylene blocks. This set-up should represent the clinical use, but available data in the literature are few. Anatomical parameters depending on the spinal level were compared to published data or measurements on biplanar stereoradiography on 13 patients. Other mechanical variables, describing implant design were considered, and all parameters were investigated using a numerical parametric finite element model. Stress values were calculated by considering either the combination of the average values for each parameter or their worst-case combination depending on the spinal level. The standard set-up represents quite well the anatomy of an instrumented average thoracolumbar segment. The stress on the pedicular screw is significantly influenced by the lever arm of the applied load, the unsupported screw length, the position of the centre of rotation of the functional spine unit and the pedicular inclination with respect to the sagittal plane. The worst-case combination of parameters demonstrates that devices implanted below T5 could potentially undergo higher stresses than those described in the standard suggestions (maximum increase of 22.2% at L1). We propose to revise F1717 in order to describe the anatomical worst case condition we found at L1 level: this will guarantee higher safety of the implant for a wider population of patients. © IMechE 2014.

Theoretical performance and clinical evaluation of transverse tripolar spinal cord stimulation.

PubMed

Struijk, J J; Holsheimer, J; Spincemaille, G H; Gielen, F L; Hoekema, R

1998-09-01

A new type of spinal cord stimulation electrode, providing contact combinations with a transverse orientation, is presented. Electrodes were implanted in the cervical area (C4-C5) of two chronic pain patients and the stimulation results were subsequently simulated with a computer model consisting of a volume conductor model and active nerve fiber models. For various contact combinations a good match was obtained between the modeling results and the measurement data with respect to load resistance (less than 20% difference), perception thresholds (16% difference), asymmetry of paresthesia (significant correlation) and paresthesia distributions (weak correlation). The transversally oriented combinations provided the possibility to select either a preferential dorsal column stimulation, a preferential dorsal root stimulation or a mixed stimulation. The (a)symmetry of paresthesia could largely be affected in a predictable way by the selection of contact combinations as well. The transverse tripolar combination was shown to give a higher selectivity of paresthesia than monopolar and longitudinal dipolar combinations, at the cost of an increased current (more than twice).

Further observations on the relationship of EMG and muscle force

NASA Technical Reports Server (NTRS)

Agarwal, G. C.; Cecchini, L. R.; Gottlieb, G. L.

1972-01-01

Human skeletal muscle may be regarded as an electro-mechanical transducer. Its physiological input is a neural signal originating at the alpha motoneurons in the spinal cord and its output is force and muscle contraction, these both being dependent on the external load. Some experimental data taken during voluntary efforts around the ankle joint and by direct electrical stimulation of the nerve are described. Some of these experiments are simulated by an analog model, the input of which is recorded physiological soleus muscle EMG. The output is simulated foot torque. Limitations of a linear model and effect of some nonlinearities are discussed.

Neural computational modeling reveals a major role of corticospinal gating of central oscillations in the generation of essential tremor.

PubMed

Qu, Hong-En; Niu, Chuanxin M; Li, Si; Hao, Man-Zhao; Hu, Zi-Xiang; Xie, Qing; Lan, Ning

2017-12-01

Essential tremor, also referred to as familial tremor, is an autosomal dominant genetic disease and the most common movement disorder. It typically involves a postural and motor tremor of the hands, head or other part of the body. Essential tremor is driven by a central oscillation signal in the brain. However, the corticospinal mechanisms involved in the generation of essential tremor are unclear. Therefore, in this study, we used a neural computational model that includes both monosynaptic and multisynaptic corticospinal pathways interacting with a propriospinal neuronal network. A virtual arm model is driven by the central oscillation signal to simulate tremor activity behavior. Cortical descending commands are classified as alpha or gamma through monosynaptic or multisynaptic corticospinal pathways, which converge respectively on alpha or gamma motoneurons in the spinal cord. Several scenarios are evaluated based on the central oscillation signal passing down to the spinal motoneurons via each descending pathway. The simulated behaviors are compared with clinical essential tremor characteristics to identify the corticospinal pathways responsible for transmitting the central oscillation signal. A propriospinal neuron with strong cortical inhibition performs a gating function in the generation of essential tremor. Our results indicate that the propriospinal neuronal network is essential for relaying the central oscillation signal and the production of essential tremor.

[The metabolic profilings study of serum and spinal cord from acute spinal cord injury rats ¹H NMR spectroscopy].

PubMed

Hu, Hua-Hui; Huang, Xiao-Long; Quan, Ren-Fu; Yang, Zong-Bao; Xu, Jing-Jing

2017-02-25

To establish the rat model of acute spinal cord injury, followed by aprimary study on this model with ¹H NMR based on metabonomics and to explore the metabonomics and biomarkers of spinal cord injury rat. Twenty eight-week-old adult male SD rats of clean grade, with body weight of (200±10) g, were divided into sham operation group and model group in accordance with the law of random numbers, and every group had 10 rats. The rats of sham operation group were operated without damaging the spinal cord, and rats of model group were made an animal model of spinal cord incomplete injury according to the modified Allen's method. According to BBB score to observate the motor function of rats on the 1th, 5th, and 7th days after surgery. Postoperative spinal cord tissue was collected in order to pathologic observation at the 7th day, and the metabolic profilings of serum and spinal cord from spinal cord injury rats were studied by ¹H NMR spectroscopy. The hindlimb motion of rats did not obviously change in sham operation group, there was no significant difference at each time point;and rats of model group occurred flaccid paralysis of both lower extremities, there was a significant difference at each time; there was significant differences between two groups at each time. Pathological results showed the spinal cord structure was normal with uniform innervation in shame group, while in model group, the spinal cord structure was mussy, and the neurons were decreased, with inflammatory cells and necrotic tissue. Analysis of metabonomics showed that concentration of very low density fat protein (VLDL), low density fat protein (LDL), glutamine, citric acid, dimethylglycine (DMG) in the serum and glutathione, 3-OH-butyrate, N-Acetyl-L-aspartic acid (NAA), glycerophosphocholine (GPC), glutamic acid, and ascorbate in spinal cord had significant changes( P <0.05). There are significant differences in metabolic profile from serum and spinal cord sample between model group and sham operation group, it conduces to explain the changes of small molecular substances in serum and spinal cord tissue after spinal cord injury, this provides the research basis for targeted research on the role of metabolic markers in patients with acute spinal cord injury.

Investigation of interstitial ultrasound ablation of spinal and paraspinal tumors: A patient-specific and parametric simulation study

NASA Astrophysics Data System (ADS)

Scott, Serena J.; Salgaonkar, Vasant; Prakash, Punit; Burdette, E. Clif; Diederich, Chris J.

2017-03-01

Preferential acoustic absorption and heating of bone can significantly impact interstitial ultrasound ablation of tumors within or bordering the spine. Furthermore, intervening cortical bone may provide acoustic and thermal insulation that can protect sensitive structures nearby, such as the spinal cord. The objectives of this study are firstly, to apply parametric and patient-specific models to theoretically assess the feasibility of interstitial ultrasound ablation of tumors within and near the spine, and secondly, to identify potential energy delivery strategies, safety criteria, advantages, and disadvantages of interstitial ultrasound in this setting. Transient biothermal models using previously validated approximations for power deposition within bone from interstitial sources were employed. Multilayered axisymmetric models were used to perform a parametric assessment of the impact of tumor dimensions, attenuation (dependent on residual bone content), perfusion, and maximum temperature thresholds on necessary treatment parameters and on treatment effectiveness. 3D patient-specific finite element models were generated based on segmented CT scans for nine representative patient cases selected to bracket a range of clinical interest, with tumors in or near the vertebrae, sacrum, and ilium. Tumors were 10-27 mm in diameter, 10-43 mm long, and 0-14 mm from the spinal canal. Paraspinal tumors, osteolytic vertebral tumors, and a mixed osteolytic/osteoblastic iliac bone tumor were considered. 7 MHz (1.5 mm OD) and 3.0 MHz (3.2 mm OD) applicators with an array of 1-4 tubular transducers (0.5 -1.5 cm long, 150-360° sector angles), were applied in various implant configurations. Variable thicknesses of bone insulating critical anatomy from the tumor and insulation of the spinal cord with injected carbon dioxide were also investigated for definition of safety margins and possible protection of critical structures. 6-44 mm diameter osteolytic tumors surrounded by bone and blastic (high bone content) lesions up to 20 mm in diameter could be fully ablated by 7 MHz interstitial ultrasound using 120-5,900 J and treatment durations of 0.4-15 min. 100% of the volumes of five simulated tumors located 4.3-14 mm from the spinal canal and 94.6-99.9% of the volumes of four simulated tumors 0-4.5 mm from the spinal canal were ablated (>240 EM43°C) within 15 min without damaging (<6 EM43°C) critical nerves. Preferential ultrasound absorption and concomitant heating at bone surfaces allowed for faster, more effective ablations with less delivered energy. 3-5 mm of normal cortical bone was found to provide a safety margin and reduce temperature elevations in untargeted tissues. Critical anatomy less than 3-5 mm from a tumor encapsulated by bone could be preserved by reducing the acoustic energy aimed towards these structures and/or through injection of insulating CO2. Parametric and patient-specific studies demonstrated the feasibility of interstitial ultrasound ablation of paraspinal tumors and osteolytic tumors within the spine. Preferential absorption of ultrasound by bone may provide improved localization, faster treatment times, and larger treatment zones in highly osteolytic and soft tissue tumors in and near bone compared to other heating modalities. This work was supported by the NIH grant R44CA112852.

Muscle activity and mood state during simulated plant factory work in individuals with cervical spinal cord injury

PubMed Central

Okahara, Satoshi; Kataoka, Masataka; Okuda, Kuniharu; Shima, Masato; Miyagaki, Keiko; Ohara, Hitoshi

2016-01-01

[Purpose] The present study investigated the physical and mental effects of plant factory work in individuals with cervical spinal cord injury and the use of a newly developed agricultural working environment. [Subjects] Six males with C5–C8 spinal cord injuries and 10 healthy volunteers participated. [Methods] Plant factory work involved three simulated repetitive tasks: sowing, transplantation, and harvesting. Surface electromyography was performed in the dominant upper arm, upper trapezius, anterior deltoid, and biceps brachii muscles. Subjects’ moods were monitored using the Profile of Mood States. [Results] Five males with C6–C8 injuries performed the same tasks as healthy persons; a male with a C5 injury performed fewer repetitions of tasks because it took longer. Regarding muscle activity during transplantation and harvesting, subjects with spinal cord injury had higher values for the upper trapezius and anterior deltoid muscles compared with healthy persons. The Profile of Mood States vigor scores were significantly higher after tasks in subjects with spinal cord injury. [Conclusion] Individuals with cervical spinal cord injury completed the plant factory work, though it required increased time and muscle activity. For individuals with C5–C8 injuries, it is necessary to develop an appropriate environment and assistive devices to facilitate their work. PMID:27134377

Development and Validation of a Statistical Shape Modeling-Based Finite Element Model of the Cervical Spine Under Low-Level Multiple Direction Loading Conditions

PubMed Central

Bredbenner, Todd L.; Eliason, Travis D.; Francis, W. Loren; McFarland, John M.; Merkle, Andrew C.; Nicolella, Daniel P.

2014-01-01

Cervical spinal injuries are a significant concern in all trauma injuries. Recent military conflicts have demonstrated the substantial risk of spinal injury for the modern warfighter. Finite element models used to investigate injury mechanisms often fail to examine the effects of variation in geometry or material properties on mechanical behavior. The goals of this study were to model geometric variation for a set of cervical spines, to extend this model to a parametric finite element model, and, as a first step, to validate the parametric model against experimental data for low-loading conditions. Individual finite element models were created using cervical spine (C3–T1) computed tomography data for five male cadavers. Statistical shape modeling (SSM) was used to generate a parametric finite element model incorporating variability of spine geometry, and soft-tissue material property variation was also included. The probabilistic loading response of the parametric model was determined under flexion-extension, axial rotation, and lateral bending and validated by comparison to experimental data. Based on qualitative and quantitative comparison of the experimental loading response and model simulations, we suggest that the model performs adequately under relatively low-level loading conditions in multiple loading directions. In conclusion, SSM methods coupled with finite element analyses within a probabilistic framework, along with the ability to statistically validate the overall model performance, provide innovative and important steps toward describing the differences in vertebral morphology, spinal curvature, and variation in material properties. We suggest that these methods, with additional investigation and validation under injurious loading conditions, will lead to understanding and mitigating the risks of injury in the spine and other musculoskeletal structures. PMID:25506051

Experimental spinal cord trauma: a review of mechanically induced spinal cord injury in rat models.

PubMed

Abdullahi, Dauda; Annuar, Azlina Ahmad; Mohamad, Masro; Aziz, Izzuddin; Sanusi, Junedah

2017-01-01

It has been shown that animal spinal cord compression (using methods such as clips, balloons, spinal cord strapping, or calibrated forceps) mimics the persistent spinal canal occlusion that is common in human spinal cord injury (SCI). These methods can be used to investigate the effects of compression or to know the optimal timing of decompression (as duration of compression can affect the outcome of pathology) in acute SCI. Compression models involve prolonged cord compression and are distinct from contusion models, which apply only transient force to inflict an acute injury to the spinal cord. While the use of forceps to compress the spinal cord is a common choice due to it being inexpensive, it has not been critically assessed against the other methods to determine whether it is the best method to use. To date, there is no available review specifically focused on the current compression methods of inducing SCI in rats; thus, we performed a systematic and comprehensive publication search to identify studies on experimental spinalization in rat models, and this review discusses the advantages and limitations of each method.

A spinal thecal sac constriction model supports the theory that induced pressure gradients in the cord cause edema and cyst formation.

PubMed

Josephson, A; Greitz, D; Klason, T; Olson, L; Spenger, C

2001-03-01

Spinal cord cysts are a devastating condition that occur secondary to obstructions of the spinal canal, which may be caused by congenital malformations, trauma, spinal canal stenosis, tumors, meningitis, or arachnoiditis. A hypothesis that could explain how spinal cord cysts form in these situations has been presented recently. Therefore, a novel spinal thecal sac constriction model was implemented to test various aspects of this hypothesis. Thecal sac constriction was achieved by subjecting rats to an extradural silk ligature at the T8 spinal cord level. Rats with complete spinal cord transection served as a second model for comparison. The animals underwent high-resolution magnetic resonance imaging and histological analysis. Thecal sac constriction caused edema cranial and caudal to the ligation within 3 weeks, and cysts developed after 8 to 13 weeks. In contrast, cysts in rats with spinal cord transection were located predominantly in the cranial spinal cord. Histological sections of spinal cords confirmed the magnetic resonance imaging results. Magnetic resonance imaging provided the specific advantage of enabling characterization of events as they occurred repeatedly over time in the spinal cords of individual living animals. The spinal thecal sac constriction model proved useful for investigation of features of the cerebrospinal fluid pulse pressure theory. Edema and cyst distributions were in accordance with this theory. We conclude that induced intramedullary pressure gradients originating from the cerebrospinal fluid pulse pressure may underlie cyst formation in the vicinity of spinal canal obstructions and that cysts are preceded by edema.

Development and evaluation of a finite element model of the THOR for occupant protection of spaceflight crewmembers.

PubMed

Putnam, Jacob B; Somers, Jeffrey T; Wells, Jessica A; Perry, Chris E; Untaroiu, Costin D

2015-09-01

New vehicles are currently being developed to transport humans to space. During the landing phases, crewmembers may be exposed to spinal and frontal loading. To reduce the risk of injuries during these common impact scenarios, the National Aeronautics and Space Administration (NASA) is developing new safety standards for spaceflight. The Test Device for Human Occupant Restraint (THOR) advanced multi-directional anthropomorphic test device (ATD), with the National Highway Traffic Safety Administration modification kit, has been chosen to evaluate occupant spacecraft safety because of its improved biofidelity. NASA tested the THOR ATD at Wright-Patterson Air Force Base (WPAFB) in various impact configurations, including frontal and spinal loading. A computational finite element model (FEM) of the THOR to match these latest modifications was developed in LS-DYNA software. The main goal of this study was to calibrate and validate the THOR FEM for use in future spacecraft safety studies. An optimization-based method was developed to calibrate the material models of the lumbar joints and pelvic flesh. Compression test data were used to calibrate the quasi-static material properties of the pelvic flesh, while whole body THOR ATD kinematic and kinetic responses under spinal and frontal loading conditions were used for dynamic calibration. The performance of the calibrated THOR FEM was evaluated by simulating separate THOR ATD tests with different crash pulses along both spinal and frontal directions. The model response was compared with test data by calculating its correlation score using the CORrelation and Analysis rating system. The biofidelity of the THOR FEM was then evaluated against tests recorded on human volunteers under 3 different frontal and spinal impact pulses. The calibrated THOR FEM responded with high similarity to the THOR ATD in all validation tests. The THOR FEM showed good biofidelity relative to human-volunteer data under spinal loading, but limited biofidelity under frontal loading. This may suggest a need for further improvements in both the THOR ATD and FEM. Overall, results presented in this study provide confidence in the THOR FEM for use in predicting THOR ATD responses for conditions, such as those observed in spacecraft landing, and for use in evaluating THOR ATD biofidelity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Planning the Surgical Correction of Spinal Deformities: Toward the Identification of the Biomechanical Principles by Means of Numerical Simulation

PubMed Central

Galbusera, Fabio; Bassani, Tito; La Barbera, Luigi; Ottardi, Claudia; Schlager, Benedikt; Brayda-Bruno, Marco; Villa, Tomaso; Wilke, Hans-Joachim

2015-01-01

In decades of technical developments after the first surgical corrections of spinal deformities, the set of devices, techniques, and tools available to the surgeons has widened dramatically. Nevertheless, the rate of complications due to mechanical failure of the fixation or the instrumentation remains rather high. Indeed, basic and clinical research about the principles of deformity correction and the optimal surgical strategies (i.e., the choice of the fusion length, the most appropriate instrumentation, and the degree of tolerable correction) did not progress as much as the implantable devices and the surgical techniques. In this work, a software approach for the biomechanical simulation of the correction of patient-specific spinal deformities aimed to the identification of its biomechanical principles is presented. The method is based on three-dimensional reconstructions of the spinal anatomy obtained from biplanar radiographic images. A user-friendly graphical user interface allows for the planning of the desired deformity correction and to simulate the implantation of pedicle screws. Robust meshing of the instrumented spine is provided by using consolidated computational geometry and meshing libraries. Based on a finite element simulation, the program is able to predict the loads and stresses acting in the instrumentation as well as those in the biological tissues. A simple test case (reduction of a low-grade spondylolisthesis at L3–L4) was simulated as a proof of concept, and showed plausible results. Despite the numerous limitations of this approach which will be addressed in future implementations, the preliminary outcome is promising and encourages a wide effort toward its refinement. PMID:26579518

Monolithic superelastic rods with variable flexural stiffness for spinal fusion: modeling of the processing-properties relationship.

PubMed

Facchinello, Yann; Brailovski, Vladimir; Petit, Yvan; Mac-Thiong, Jean-Marc

2014-11-01

The concept of a monolithic Ti-Ni spinal rod with variable flexural stiffness is proposed to reduce the risks associated with spinal fusion. The variable stiffness is conferred to the rod using the Joule-heating local annealing technique. The annealing temperature and the mechanical properties' distributions resulted from this thermal treatment are numerically modeled and experimentally measured. To illustrate the possible applications of such a modeling approach, two case studies are presented: (a) optimization of the Joule-heating strategy to reduce annealing time, and (b) modulation of the rod's overall flexural stiffness using partial annealing. A numerical model of a human spine coupled with the model of the variable flexural stiffness spinal rod developed in this work can ultimately be used to maximize the stabilization capability of spinal instrumentation, while simultaneously decreasing the risks associated with spinal fusion. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

Lumbar spinal loading during bowling in cricket: a kinetic analysis using a musculoskeletal modelling approach.

PubMed

Zhang, Yanxin; Ma, Ye; Liu, Guangyu

2016-01-01

The objective of the study was to evaluate two types of cricket bowling techniques by comparing the lumbar spinal loading using a musculoskeletal modelling approach. Three-dimensional kinematic data were recorded by a Vicon motion capture system under two cricket bowling conditions: (1) participants bowled at their absolute maximal speeds (max condition), and (2) participants bowled at their absolute maximal speeds while simultaneously forcing their navel down towards their thighs starting just prior to ball release (max-trunk condition). A three-dimensional musculoskeletal model comprised of the pelvis, sacrum, lumbar vertebrae and torso segments, which enabled the motion of the individual lumbar vertebrae in the sagittal, frontal and coronal planes to be actuated by 210 muscle-tendon units, was used to simulate spinal loading based on the recorded kinematic data. The maximal lumbar spine compressive force is 4.89 ± 0.88BW for the max condition and 4.58 ± 0.54BW for the max-trunk condition. Results showed that there was no significant difference between the two techniques in trunk moments and lumbar spine forces. This indicates that the max-trunk technique may not increase lower back injury risks. The method proposed in this study could be served as a tool to evaluate lower back injury risks for cricket bowling as well as other throwing activities.

Compressive mechanical characterization of non-human primate spinal cord white matter.

PubMed

Jannesar, Shervin; Allen, Mark; Mills, Sarah; Gibbons, Anne; Bresnahan, Jacqueline C; Salegio, Ernesto A; Sparrey, Carolyn J

2018-05-02

The goal of developing computational models of spinal cord injury (SCI) is to better understand the human injury condition. However, finite element models of human SCI have used rodent spinal cord tissue properties due to a lack of experimental data. Central nervous system tissues in non human primates (NHP) closely resemble that of humans and therefore, it is expected that material constitutive models obtained from NHPs will increase the fidelity and the accuracy of human SCI models. Human SCI most often results from compressive loading and spinal cord white matter properties affect FE predicted patterns of injury; therefore, the objectives of this study were to characterize the unconfined compressive response of NHP spinal cord white matter and present an experimentally derived, finite element tractable constitutive model for the tissue. Cervical spinal cords were harvested from nine male adult NHPs (Macaca mulatta). White matter biopsy samples (3 mm in diameter) were taken from both lateral columns of the spinal cord and were divided into four strain rate groups for unconfined dynamic compression and stress relaxation (post-mortem <1-hour). The NHP spinal cord white matter compressive response was sensitive to strain rate and showed substantial stress relaxation confirming the viscoelastic behavior of the material. An Ogden 1st order model best captured the non-linear behavior of NHP white matter in a quasi-linear viscoelastic material model with 4-term Prony series. This study is the first to characterize NHP spinal cord white matter at high (>10/sec) strain rates typical of traumatic injury. The finite element derived material constitutive model of this study will increase the fidelity of SCI computational models and provide important insights for transferring pre-clinical findings to clinical treatments. Spinal cord injury (SCI) finite element (FE) models provide an important tool to bridge the gap between animal studies and human injury, assess injury prevention technologies (e.g. helmets, seatbelts), and provide insight into the mechanisms of injury. Although, FE model outcomes depend on the assumed material constitutive model, there is limited experimental data for fresh spinal cords and all was obtained from rodent, porcine or bovine tissues. Central nervous system tissues in non human primates (NHP) more closely resemble humans. This study characterizes fresh NHP spinal cord material properties at high strains rates and large deformations typical of SCI for the first time. A constitutive model was defined that can be readily implemented in finite strain FE analysis of SCI. Copyright © 2018. Published by Elsevier Ltd.

Virtual endoscopic imaging of the spine.

PubMed

Kotani, Toshiaki; Nagaya, Shigeyuki; Sonoda, Masaru; Akazawa, Tsutomu; Lumawig, Jose Miguel T; Nemoto, Tetsuharu; Koshi, Takana; Kamiya, Koshiro; Hirosawa, Naoya; Minami, Shohei

2012-05-20

Prospective trial of virtual endoscopy in spinal surgery. To investigate the utility of virtual endoscopy of the spine in conjunction with spinal surgery. Several studies have described clinical applications of virtual endoscopy to visualize the inside of the bronchi, paranasal sinus, stomach, small intestine, pancreatic duct, and bile duct, but, to date, no study has described the use of virtual endoscopy in the spine. Virtual endoscopy is a realistic 3-dimensional intraluminal simulation of tubular structures that is generated by postprocessing of computed tomographic data sets. Five patients with spinal disease were selected: 2 patients with degenerative disease, 2 patients with spinal deformity, and 1 patient with spinal injury. Virtual endoscopy software allows an observer to explore the spinal canal with a mouse, using multislice computed tomographic data. Our study found that virtual endoscopy of the spine has advantages compared with standard imaging methods because surgeons can noninvasively explore the spinal canal in all directions. Virtual endoscopy of the spine may be useful to surgeons for diagnosis, preoperative planning, and postoperative assessment by obviating the need to mentally construct a 3-dimensional picture of the spinal canal from 2-dimensional computed tomographic scans.

p53 participates in the protective effects of ischemic post-conditioning against OGD-reperfusion injury in primary cultured spinal cord neurons.

PubMed

Li, Jinquan; Chen, Gong; Gao, Xinjie; Shen, Chao; Zhou, Ping; Wu, Xing; Che, Xiaoming; Xie, Rong

2017-01-18

Spinal cord ischemia-reperfusion (I/R) injury is a severe clinical condition, while the mechanism is still not clarified and the therapeutic approach is limited. Ischemia post-conditioning (PC) has been found to have the protective effects against I/R injury in brain. Recently p53 has been reported to take part in the regulation and protection of I/R injury. We hypothesize that PC has the protective effects in primary cultured spinal cord neurons against ischemia-reperfusion injury, and MDM2-p53 signaling pathway may involve in its protective mechanism. In this study, we used an OGD (oxygen and glucose deprivation)-reperfusion model in primary cultured spinal cord neurons to simulate the I/R injury of spinal cord in vitro, and PC was conducted by 3 cycles of 15min restoration of glucose and oxygen with 15min OGD, followed by 6h fully restoration as reperfusion. Lentiviral vectors were used to knock down MDM2 or over-express p53 genes in primary cultured spinal cord neurons. The results showed that 3 cycles of 15min PC generated the most significant protective effects in primary cultured spinal cord neurons against OGD-reperfusion injury. The levels of MDM2 were decreased while p53, Bax, and cleaved Caspase 3 were increased under OGD-reperfusion condition. PC could significantly reverse the down-regulation of MDM2 and up-regulation of p53, Bax, and cleaved Caspase 3 by OGD-reperfusion injury. Moreover, MDM2 knockdown or p53 over-expression could induce the cleaved Caspase 3 expression and blocked the protective effects of PC in primary cultured spinal cord neurons against OGD-reperfusion injury. In conclusion, our work demonstrated that MDM2-p53 pathway plays a pivotal role in the protective effect of PC against OGD-reperfusion injury and PC may be a feasible therapy strategy in the treatment for spinal cord I/R injury. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Numerical Cerebrospinal System Modeling in Fluid-Structure Interaction.

PubMed

Garnotel, Simon; Salmon, Stéphanie; Balédent, Olivier

2018-01-01

Cerebrospinal fluid (CSF) stroke volume in the aqueduct is widely used to evaluate CSF dynamics disorders. In a healthy population, aqueduct stroke volume represents around 10% of the spinal stroke volume while intracranial subarachnoid space stroke volume represents 90%. The amplitude of the CSF oscillations through the different compartments of the cerebrospinal system is a function of the geometry and the compliances of each compartment, but we suspect that it could also be impacted be the cardiac cycle frequency. To study this CSF distribution, we have developed a numerical model of the cerebrospinal system taking into account cerebral ventricles, intracranial subarachnoid spaces, spinal canal and brain tissue in fluid-structure interactions. A numerical fluid-structure interaction model is implemented using a finite-element method library to model the cerebrospinal system and its interaction with the brain based on fluid mechanics equations and linear elasticity equations coupled in a monolithic formulation. The model geometry, simplified in a first approach, is designed in accordance with realistic volume ratios of the different compartments: a thin tube is used to mimic the high flow resistance of the aqueduct. CSF velocity and pressure and brain displacements are obtained as simulation results, and CSF flow and stroke volume are calculated from these results. Simulation results show a significant variability of aqueduct stroke volume and intracranial subarachnoid space stroke volume in the physiological range of cardiac frequencies. Fluid-structure interactions are numerous in the cerebrospinal system and difficult to understand in the rigid skull. The presented model highlights significant variations of stroke volumes under cardiac frequency variations only.

Transcutaneous spinal direct current stimulation of the lumbar and sacral spinal cord: a modelling study

NASA Astrophysics Data System (ADS)

Fernandes, Sofia R.; Salvador, Ricardo; Wenger, Cornelia; de Carvalho, Mamede; Miranda, Pedro C.

2018-06-01

Objective. Our aim was to perform a computational study of the electric field (E-field) generated by transcutaneous spinal direct current stimulation (tsDCS) applied over the thoracic, lumbar and sacral spinal cord, in order to assess possible neuromodulatory effects on spinal cord circuitry related with lower limb functions. Approach. A realistic volume conductor model of the human body consisting of 14 tissues was obtained from available databases. Rubber pad electrodes with a metallic connector and a conductive gel layer were modelled. The finite element (FE) method was used to calculate the E-field when a current of 2.5 mA was passed between two electrodes. The main characteristics of the E-field distributions in the spinal grey matter (spinal-GM) and spinal white matter (spinal-WM) were compared for seven montages, with the anode placed either over T10, T8 or L2 spinous processes (s.p.), and the cathode placed over right deltoid (rD), umbilicus (U) and right iliac crest (rIC) areas or T8 s.p. Anisotropic conductivity of spinal-WM and of a group of dorsal muscles near the vertebral column was considered. Main results. The average E-field magnitude was predicted to be above 0.15 V m-1 in spinal cord regions located between the electrodes. L2-T8 and T8-rIC montages resulted in the highest E-field magnitudes in lumbar and sacral spinal segments (>0.30 V m-1). E-field longitudinal component is 3 to 6 times higher than the ventral-dorsal and right-left components in both the spinal-GM and WM. Anatomical features such as CSF narrowing due to vertebrae bony edges or disks intrusions in the spinal canal correlate with local maxima positions. Significance. Computational modelling studies can provide detailed information regarding the electric field in the spinal cord during tsDCS. They are important to guide the design of clinical tsDCS protocols that optimize stimulation of application-specific spinal targets.

Percutaneous spinal fixation simulation with virtual reality and haptics.

PubMed

Luciano, Cristian J; Banerjee, P Pat; Sorenson, Jeffery M; Foley, Kevin T; Ansari, Sameer A; Rizzi, Silvio; Germanwala, Anand V; Kranzler, Leonard; Chittiboina, Prashant; Roitberg, Ben Z

2013-01-01

In this study, we evaluated the use of a part-task simulator with 3-dimensional and haptic feedback as a training tool for percutaneous spinal needle placement. To evaluate the learning effectiveness in terms of entry point/target point accuracy of percutaneous spinal needle placement on a high-performance augmented-reality and haptic technology workstation with the ability to control the duration of computer-simulated fluoroscopic exposure, thereby simulating an actual situation. Sixty-three fellows and residents performed needle placement on the simulator. A virtual needle was percutaneously inserted into a virtual patient's thoracic spine derived from an actual patient computed tomography data set. Ten of 126 needle placement attempts by 63 participants ended in failure for a failure rate of 7.93%. From all 126 needle insertions, the average error (15.69 vs 13.91), average fluoroscopy exposure (4.6 vs 3.92), and average individual performance score (32.39 vs 30.71) improved from the first to the second attempt. Performance accuracy yielded P = .04 from a 2-sample t test in which the rejected null hypothesis assumes no improvement in performance accuracy from the first to second attempt in the test session. The experiments showed evidence (P = .04) of performance accuracy improvement from the first to the second percutaneous needle placement attempt. This result, combined with previous learning retention and/or face validity results of using the simulator for open thoracic pedicle screw placement and ventriculostomy catheter placement, supports the efficacy of augmented reality and haptics simulation as a learning tool.

Thoracolumbar spine loading associated with kinematics of the young and the elderly during activities of daily living.

PubMed

Ignasiak, Dominika; Rüeger, Andrea; Sperr, Ramona; Ferguson, Stephen J

2018-03-21

Excessive mechanical loading of the spine is a critical factor in vertebral fracture initiation. Most vertebral fractures develop spontaneously or due to mild trauma, as physiological loads during activities of daily living might exceed the failure load of osteoporotic vertebra. Spinal loading patterns are affected by vertebral kinematics, which differ between elderly and young individuals. In this study, the effects of age-related changes in spine kinematics on thoracolumbar spinal segmental loading during dynamic activities of daily living were investigated using combined experimental and modeling approach. Forty-four healthy volunteers were recruited into two age groups: young (N = 23, age = 27.1 ± 3.8) and elderly (N = 21, age = 70.1 ± 3.9). The spinal curvature was assessed with a skin-surface device and the kinematics of the spine and lower extremities were recorded during daily living tasks (flexion-extension and stand-sit-stand) with a motion capture system. The obtained data were used as input for a musculoskeletal model with a detailed thoracolumbar spine representation. To isolate the effect of kinematics on predicted loads, other model properties were kept constant. Inverse dynamics simulations were performed in the AnyBody Modeling System to estimate corresponding spinal loads. The maximum compressive loads predicted for the elderly motion patterns were lower than those of the young for L2/L3 and L3/L4 lumbar levels during flexion and for upper thoracic levels during stand-to-sit (T1/T2-T8/T9) and sit-to-stand (T3/T4-T6/T7). However, the maximum loads predicted for the lower thoracic levels (T9/T10-L1/L2), a common site of vertebral fractures, were similar compared to the young. Nevertheless, these loads acting on the vertebrae of reduced bone quality might contribute to a higher fracture risk for the elderly. Copyright © 2017 Elsevier Ltd. All rights reserved.

Public Regulatory Databases as a Source of Insight for Neuromodulation Devices Stimulation Parameters

PubMed Central

Kumsa, Doe; Steinke, G. Karl; Molnar, Gregory F.; Hudak, Eric M.; Montague, Fred W.; Kelley, Shawn C.; Untereker, Darrel F.; Shi, Alan; Hahn, Benjamin P.; Condit, Chris; Lee, Hyowon; Bardot, Dawn; Centeno, Jose A.; Krauthamer, Victor; Takmakov, Pavel A.

2017-01-01

Objective The Shannon model is often used to define an expected boundary between non-damaging and damaging modes of electrical neurostimulation. Numerous preclinical studies have been performed by manufacturers of neuromodulation devices using different animal models and a broad range of stimulation parameters while developing devices for clinical use. These studies are mostly absent from peer-reviewed literature, which may lead to this information being overlooked by the scientific community. We aimed to locate summaries of these studies accessible via public regulatory databases and to add them to a body of knowledge available to a broad scientific community. Methods We employed web search terms describing device type, intended use, neural target, therapeutic application, company name, and submission number to identify summaries for premarket approval (PMA) devices and 510(k) devices. We filtered these records to a subset of entries that have sufficient technical information relevant to safety of neurostimulation. Results We identified 13 product codes for 8 types of neuromodulation devices. These led us to devices that have 22 PMAs and 154 510(k)s and six transcripts of public panel meetings. We found one PMA for a brain, peripheral nerve, and spinal cord stimulator and five 510(k) spinal cord stimulators with enough information to plot in Shannon coordinates of charge and charge density per phase. Conclusions Analysis of relevant entries from public regulatory databases reveals use of pig, sheep, monkey, dog, and goat animal models with deep brain, peripheral nerve, muscle and spinal cord electrode placement with a variety of stimulation durations (hours to years); frequencies (10–10,000 Hz) and magnitudes (Shannon k from below zero to 4.47). Data from located entries indicate that a feline cortical model that employs acute stimulation might have limitations for assessing tissue damage in diverse anatomical locations, particularly for peripheral nerve and spinal cord simulation. PMID:28782181

Public Regulatory Databases as a Source of Insight for Neuromodulation Devices Stimulation Parameters.

PubMed

Kumsa, Doe; Steinke, G Karl; Molnar, Gregory F; Hudak, Eric M; Montague, Fred W; Kelley, Shawn C; Untereker, Darrel F; Shi, Alan; Hahn, Benjamin P; Condit, Chris; Lee, Hyowon; Bardot, Dawn; Centeno, Jose A; Krauthamer, Victor; Takmakov, Pavel A

2018-02-01

The Shannon model is often used to define an expected boundary between non-damaging and damaging modes of electrical neurostimulation. Numerous preclinical studies have been performed by manufacturers of neuromodulation devices using different animal models and a broad range of stimulation parameters while developing devices for clinical use. These studies are mostly absent from peer-reviewed literature, which may lead to this information being overlooked by the scientific community. We aimed to locate summaries of these studies accessible via public regulatory databases and to add them to a body of knowledge available to a broad scientific community. We employed web search terms describing device type, intended use, neural target, therapeutic application, company name, and submission number to identify summaries for premarket approval (PMA) devices and 510(k) devices. We filtered these records to a subset of entries that have sufficient technical information relevant to safety of neurostimulation. We identified 13 product codes for 8 types of neuromodulation devices. These led us to devices that have 22 PMAs and 154 510(k)s and six transcripts of public panel meetings. We found one PMA for a brain, peripheral nerve, and spinal cord stimulator and five 510(k) spinal cord stimulators with enough information to plot in Shannon coordinates of charge and charge density per phase. Analysis of relevant entries from public regulatory databases reveals use of pig, sheep, monkey, dog, and goat animal models with deep brain, peripheral nerve, muscle and spinal cord electrode placement with a variety of stimulation durations (hours to years); frequencies (10-10,000 Hz) and magnitudes (Shannon k from below zero to 4.47). Data from located entries indicate that a feline cortical model that employs acute stimulation might have limitations for assessing tissue damage in diverse anatomical locations, particularly for peripheral nerve and spinal cord simulation. © 2017 International Neuromodulation Society.

A pilot study of the utility of a laboratory-based spinal fixation training program for neurosurgical residents.

PubMed

Sundar, Swetha J; Healy, Andrew T; Kshettry, Varun R; Mroz, Thomas E; Schlenk, Richard; Benzel, Edward C

2016-05-01

OBJECTIVE Pedicle and lateral mass screw placement is technically demanding due to complex 3D spinal anatomy that is not easily visualized. Neurosurgical and orthopedic surgery residents must be properly trained in such procedures, which can be associated with significant complications and associated morbidity. Current training in pedicle and lateral mass screw placement involves didactic teaching and supervised placement in the operating room. The objective of this study was to assess whether teaching residents to place pedicle and lateral mass screws using navigation software, combined with practice using cadaveric specimens and Sawbones models, would improve screw placement accuracy. METHODS This was a single-blinded, prospective, randomized pilot study with 8 junior neurosurgical residents and 2 senior medical students with prior neurosurgery exposure. Both the study group and the level of training-matched control group (each group with 4 level of training-matched residents and 1 senior medical student) were exposed to a standardized didactic education regarding spinal anatomy and screw placement techniques. The study group was exposed to an additional pilot program that included a training session using navigation software combined with cadaveric specimens and accessibility to Sawbones models. RESULTS A statistically significant reduction in overall surgical error was observed in the study group compared with the control group (p = 0.04). Analysis by spinal region demonstrated a significant reduction in surgical error in the thoracic and lumbar regions in the study group compared with controls (p = 0.02 and p = 0.04, respectively). The study group also was observed to place screws more optimally in the cervical, thoracic, and lumbar regions (p = 0.02, p = 0.04, and p = 0.04, respectively). CONCLUSIONS Surgical resident education in pedicle and lateral mass screw placement is a priority for training programs. This study demonstrated that compared with a didactic-only training model, using navigation simulation with cadavers and Sawbones models significantly reduced the number of screw placement errors in a laboratory setting.

Technique of spinal cord compression induced by inflation of epidural balloon catheter in rabbits (Oryctologus cuniculus): efficient and easy to use model.

PubMed

Fonseca, Antonio F B DA; Scheffer, Jussara P; Coelho, Barbara P; Aiello, Graciane; Guimarães, Arthur G; Gama, Carlos R B; Vescovini, Victor; Cabral, Paula G A; Oliveira, André L A

2016-09-01

The most common cause of spinal cord injury are high impact trauma, which often result in some motor impairment, sensory or autonomic a greater or lesser extent in the distal areas the level of trauma. In terms of survival and complications due to sequelae, veterinary patients have a poor prognosis unfavorable. Therefore justified the study of experimental models of spinal cord injury production that could provide more support to research potential treatments for spinal cord injuries in medicine and veterinary medicine. Preclinical studies of acute spinal cord injury require an experimental animal model easily reproducible. The most common experimental animal model is the rat, and several techniques for producing a spinal cord injury. The objective of this study was to describe and evaluate the effectiveness of acute spinal cord injury production technique through inflation of Fogarty(r) catheter using rabbits as an experimental model because it is a species that has fewer conclusive publications and contemplating. The main requirements of a model as low cost, handling convenience, reproducibility and uniformity. The technique was adequate for performing preclinical studies in neuro-traumatology area, effectively leading to degeneration and necrosis of the nervous tissue fostering the emergence of acute paraplegia.

Biomechanics of coupled motion in the cervical spine during simulated whiplash in patients with pre-existing cervical or lumbar spinal fusion

PubMed Central

Huang, H.; Nightingale, R. W.

2018-01-01

Objectives Loss of motion following spine segment fusion results in increased strain in the adjacent motion segments. However, to date, studies on the biomechanics of the cervical spine have not assessed the role of coupled motions in the lumbar spine. Accordingly, we investigated the biomechanics of the cervical spine following cervical fusion and lumbar fusion during simulated whiplash using a whole-human finite element (FE) model to simulate coupled motions of the spine. Methods A previously validated FE model of the human body in the driver-occupant position was used to investigate cervical hyperextension injury. The cervical spine was subjected to simulated whiplash exposure in accordance with Euro NCAP (the European New Car Assessment Programme) testing using the whole human FE model. The coupled motions between the cervical spine and lumbar spine were assessed by evaluating the biomechanical effects of simulated cervical fusion and lumbar fusion. Results Peak anterior longitudinal ligament (ALL) strain ranged from 0.106 to 0.382 in a normal spine, and from 0.116 to 0.399 in a fused cervical spine. Strain increased from cranial to caudal levels. The mean strain increase in the motion segment immediately adjacent to the site of fusion from C2-C3 through C5-C6 was 26.1% and 50.8% following single- and two-level cervical fusion, respectively (p = 0.03, unpaired two-way t-test). Peak cervical strains following various lumbar-fusion procedures were 1.0% less than those seen in a healthy spine (p = 0.61, two-way ANOVA). Conclusion Cervical arthrodesis increases peak ALL strain in the adjacent motion segments. C3-4 experiences greater changes in strain than C6-7. Lumbar fusion did not have a significant effect on cervical spine strain. Cite this article: H. Huang, R. W. Nightingale, A. B. C. Dang. Biomechanics of coupled motion in the cervical spine during simulated whiplash in patients with pre-existing cervical or lumbar spinal fusion: A Finite Element Study. Bone Joint Res 2018;7:28–35. DOI: 10.1302/2046-3758.71.BJR-2017-0100.R1. PMID:29330341

Biomechanics of coupled motion in the cervical spine during simulated whiplash in patients with pre-existing cervical or lumbar spinal fusion: A Finite Element Study.

PubMed

Huang, H; Nightingale, R W; Dang, A B C

2018-01-01

Loss of motion following spine segment fusion results in increased strain in the adjacent motion segments. However, to date, studies on the biomechanics of the cervical spine have not assessed the role of coupled motions in the lumbar spine. Accordingly, we investigated the biomechanics of the cervical spine following cervical fusion and lumbar fusion during simulated whiplash using a whole-human finite element (FE) model to simulate coupled motions of the spine. A previously validated FE model of the human body in the driver-occupant position was used to investigate cervical hyperextension injury. The cervical spine was subjected to simulated whiplash exposure in accordance with Euro NCAP (the European New Car Assessment Programme) testing using the whole human FE model. The coupled motions between the cervical spine and lumbar spine were assessed by evaluating the biomechanical effects of simulated cervical fusion and lumbar fusion. Peak anterior longitudinal ligament (ALL) strain ranged from 0.106 to 0.382 in a normal spine, and from 0.116 to 0.399 in a fused cervical spine. Strain increased from cranial to caudal levels. The mean strain increase in the motion segment immediately adjacent to the site of fusion from C2-C3 through C5-C6 was 26.1% and 50.8% following single- and two-level cervical fusion, respectively (p = 0.03, unpaired two-way t -test). Peak cervical strains following various lumbar-fusion procedures were 1.0% less than those seen in a healthy spine (p = 0.61, two-way ANOVA). Cervical arthrodesis increases peak ALL strain in the adjacent motion segments. C3-4 experiences greater changes in strain than C6-7. Lumbar fusion did not have a significant effect on cervical spine strain. Cite this article : H. Huang, R. W. Nightingale, A. B. C. Dang. Biomechanics of coupled motion in the cervical spine during simulated whiplash in patients with pre-existing cervical or lumbar spinal fusion: A Finite Element Study. Bone Joint Res 2018;7:28-35. DOI: 10.1302/2046-3758.71.BJR-2017-0100.R1. © 2018 Huang et al.

Functional characterization of mouse spinal cord infiltrating CD8+ lymphocytes

PubMed Central

Deb, Chandra; Howe, Charles L

2011-01-01

Understanding the immunopathogenesis of neuroimmunological diseases of the CNS requires a robust method for isolating and characterizing the immune effector cells that infiltrate the spinal cord in animal models. We have developed a simple and rapid isolation method that produces high yields of spinal cord infiltrating leukocytes from a single demyelinated spinal cord and which maintains high surface expression of key immunophenotyping antigens. Using this method and the Theiler’s virus model of chronic demyelination, we report the presence of spinal cord infiltrating acute effector CD8+ lymphocytes that are CD45hiCD44loCD62L− and a population of spinal cord infiltrating target effector memory CD8+ lymphocytes that are CD45hiCD44hiCD62L−. These cells respond robustly to ex vivo stimulation by producing interferon γ but do not exhibit specificity for Theiler’s virus in a cytotoxicity assay. We conclude that target-derived lymphocytes in a mouse model of chronic spinal cord demyelination may have unique functional specificities. PMID:19596449

TU-H-CAMPUS-IeP1-04: Combined Organ Dose for Digital Subtraction Angiography and Computed Tomography Using Monte Carlo Simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakabe, D; Ohno, T; Araki, F

Purpose: The purpose of this study was to evaluate the combined organ dose of digital subtraction angiography (DSA) and computed tomography (CT) using a Monte Carlo (MC) simulation on the abdominal intervention. Methods: The organ doses for DSA and CT were obtained with MC simulation and actual measurements using fluorescent-glass dosimeters at 7 abdominal portions in an Alderson-Rando phantom. DSA was performed from three directions: posterior anterior (PA), right anterior oblique (RAO), and left anterior oblique (LAO). The organ dose with MC simulation was compared with actual radiation dose measurements. Calculations for the MC simulation were carried out with themore » GMctdospp (IMPS, Germany) software based on the EGSnrc MC code. Finally, the combined organ dose for DSA and CT was calculated from the MC simulation using the X-ray conditions of a patient with a diagnosis of hepatocellular carcinoma. Results: For DSA from the PA direction, the organ doses for the actual measurements and MC simulation were 2.2 and 2.4 mGy/100 mAs at the liver, respectively, and 3.0 and 3.1 mGy/100 mAs at the spinal cord, while for CT, the organ doses were 15.2 and 15.1 mGy/100 mAs at the liver, and 14.6 and 13.5 mGy/100 mAs at the spinal cord. The maximum difference in organ dose between the actual measurements and the MC simulation was 11.0% of the spleen at PA, 8.2% of the spinal cord at RAO, and 6.1% of left kidney at LAO with DSA and 9.3% of the stomach with CT. The combined organ dose (4 DSAs and 6 CT scans) with the use of actual patient conditions was found to be 197.4 mGy for the liver and 205.1 mGy for the spinal cord. Conclusion: Our method makes it possible to accurately assess the organ dose to patients for abdominal intervention with combined DSA and CT.« less

Effect of Polyether Ether Ketone on Therapeutic Radiation to the Spine: A Pilot Study.

PubMed

Jackson, J Benjamin; Crimaldi, Anthony J; Peindl, Richard; Norton, H James; Anderson, William E; Patt, Joshua C

2017-01-01

Cadaveric model. To compare the effect of PEEK versus conventional implants on scatter radiation to a simulated tumor bed in the spine SUMMARY OF BACKGROUND DATA.: Given the highly vasculature nature of the spine, it is the most common place for bony metastases. After surgical treatment of a spinal metastasis, adjuvant radiation therapy is typically administered. Radiation dosing is primarily limited by toxicity to the spinal cord. The scatter effect caused by metallic implants decreases the accuracy of dosing and can unintentionally increase the effective dose seen by the spinal cord. This represents a dose-limiting factor for therapeutic radiation postoperatively. A cadaveric thorax specimen was utilized as a metastatic tumor model with two separate three-level spine constructs (one upper thoracic and one lower thoracic). Each construct was examined independently. All four groups compared included identical posterior instrumentation. The anterior constructs consisted of either: an anterior polyether ether ketone (PEEK) cage, an anterior titanium cage, an anterior bone cement cage (polymethyl methacrylate), or a control group with posterior instrumentation alone. Each construct had six thermoluminescent detectors to measure the radiation dose. The mean dose was similar across all constructs and locations. There was more variability in the upper thoracic spine irrespective of the construct type. The PEEK construct had a more uniform dose distribution with a standard deviation of 9.76. The standard deviation of the others constructs was 14.26 for the control group, 19.31 for the titanium cage, and 21.57 for the cement (polymethyl methacrylate) construct. The PEEK inter-body cage resulted in a significantly more uniform distribution of therapeutic radiation in the spine when compared with the other constructs. This may allow for the application of higher effective dosing to the tumor bed for spinal metastases without increasing spinal cord toxicity with either fractionated or hypofractionated radiotherapy. N/A.

The negotiated equilibrium model of spinal cord function.

PubMed

Wolpaw, Jonathan R

2018-04-16

The belief that the spinal cord is hardwired is no longer tenable. Like the rest of the CNS, the spinal cord changes during growth and aging, when new motor behaviours are acquired, and in response to trauma and disease. This paper describes a new model of spinal cord function that reconciles its recently appreciated plasticity with its long recognized reliability as the final common pathway for behaviour. According to this model, the substrate of each motor behaviour comprises brain and spinal plasticity: the plasticity in the brain induces and maintains the plasticity in the spinal cord. Each time a behaviour occurs, the spinal cord provides the brain with performance information that guides changes in the substrate of the behaviour. All the behaviours in the repertoire undergo this process concurrently; each repeatedly induces plasticity to preserve its key features despite the plasticity induced by other behaviours. The aggregate process is a negotiation among the behaviours: they negotiate the properties of the spinal neurons and synapses that they all use. The ongoing negotiation maintains the spinal cord in an equilibrium - a negotiated equilibrium - that serves all the behaviours. This new model of spinal cord function is supported by laboratory and clinical data, makes predictions borne out by experiment, and underlies a new approach to restoring function to people with neuromuscular disorders. Further studies are needed to test its generality, to determine whether it may apply to other CNS areas such as the cerebral cortex, and to develop its therapeutic implications. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Changes in neuronal properties and spinal reflexes during development of spasticity following spinal cord lesions and stroke: studies in animal models and patients.

PubMed

Hultborn, Hans

2003-05-01

It is a well-known fact that spinal reflexes may gradually change and often become enhanced following spinal cord lesions. Although these phenomena are known, the underlying mechanisms are still unknown and under investigation, mainly in animal models. Over the last twenty years, new methods have been developed that can reliably estimate the activity of specific spinal pathways in humans at rest and during voluntary movement. These methods now make it possible to describe components of the spinal pathophysiology in spasticity in humans following spinal lesions or stroke. We now know that spinal networks are capable of generating the basic pattern of locomotion in a large number of vertebrates, including the monkey--and in all likelihood, humans. Although spinal networks are capable of generating locomotor-like activity in the absence of afferent signals, functional gait is not possible without sensory feedback. The results of animal studies on the sensory control of and the transmitter systems involved in the spinal locomotor centers are now being used to improve rehabilitation of walking in persons with spinal cord injury and hemiplegia.

Labyrinth and cerebral-spinal fluid pressure changes in guinea pigs and monkeys during simulated zero G

NASA Technical Reports Server (NTRS)

Parker, D. E.

1977-01-01

This study was undertaken to explore the hypothesis that shifts of body fluids from the legs and torso toward the head contribute to the motion sickness experienced by astronauts and cosmonauts. The shifts in body fluids observed during zero-G exposure were simulated by elevating guinea pigs' and monkeys' torsos and hindquarters. Cerebral-spinal fluid pressure was recorded from a transducer located in a brain ventricle; labyrinth fluid pressure was recorded from a pipette cemented in a hole in a semicircular canal. An anticipated divergence in cerebral-spinal fluid pressure and labyrinth fluid pressure during torso elevation was not observed. The results of this study do not support a fluid shift mechanism of zero-G-induced motion sickness. However, a more complete test of the fluid shift mechanism would be obtained if endolymph and perilymph pressure changes were determined separately; we have been unable to perform this test to date.

Evaluating diagnosis-based risk-adjustment methods in a population with spinal cord dysfunction.

PubMed

Warner, Grace; Hoenig, Helen; Montez, Maria; Wang, Fei; Rosen, Amy

2004-02-01

To examine performance of models in predicting health care utilization for individuals with spinal cord dysfunction. Regression models compared 2 diagnosis-based risk-adjustment methods, the adjusted clinical groups (ACGs) and diagnostic cost groups (DCGs). To improve prediction, we added to our model: (1) spinal cord dysfunction-specific diagnostic information, (2) limitations in self-care function, and (3) both 1 and 2. Models were replicated in 3 populations. Samples from 3 populations: (1) 40% of veterans using Veterans Health Administration services in fiscal year 1997 (FY97) (N=1,046,803), (2) veteran sample with spinal cord dysfunction identified by codes from the International Statistical Classification of Diseases, 9th Revision, Clinical Modifications (N=7666), and (3) veteran sample identified in Veterans Affairs Spinal Cord Dysfunction Registry (N=5888). Not applicable. Inpatient, outpatient, and total days of care in FY97. The DCG models (R(2) range,.22-.38) performed better than ACG models (R(2) range,.04-.34) for all outcomes. Spinal cord dysfunction-specific diagnostic information improved prediction more in the ACG model than in the DCG model (R(2) range for ACG,.14-.34; R(2) range for DCG,.24-.38). Information on self-care function slightly improved performance (R(2) range increased from 0 to.04). The DCG risk-adjustment models predicted health care utilization better than ACG models. ACG model prediction was improved by adding information.

Modeling spinal cord biomechanics

NASA Astrophysics Data System (ADS)

Luna, Carlos; Shah, Sameer; Cohen, Avis; Aranda-Espinoza, Helim

2012-02-01

Regeneration after spinal cord injury is a serious health issue and there is no treatment for ailing patients. To understand regeneration of the spinal cord we used a system where regeneration occurs naturally, such as the lamprey. In this work, we analyzed the stress response of the spinal cord to tensile loading and obtained the mechanical properties of the cord both in vitro and in vivo. Physiological measurements showed that the spinal cord is pre-stressed to a strain of 10%, and during sinusoidal swimming, there is a local strain of 5% concentrated evenly at the mid-body and caudal sections. We found that the mechanical properties are homogeneous along the body and independent of the meninges. The mechanical behavior of the spinal cord can be characterized by a non-linear viscoelastic model, described by a modulus of 20 KPa for strains up to 15% and a modulus of 0.5 MPa for strains above 15%, in agreement with experimental data. However, this model does not offer a full understanding of the behavior of the spinal cord fibers. Using polymer physics we developed a model that relates the stress response as a function of the number of fibers.

Spinal circuits can accommodate interaction torques during multijoint limb movements.

PubMed

Buhrmann, Thomas; Di Paolo, Ezequiel A

2014-01-01

The dynamic interaction of limb segments during movements that involve multiple joints creates torques in one joint due to motion about another. Evidence shows that such interaction torques are taken into account during the planning or control of movement in humans. Two alternative hypotheses could explain the compensation of these dynamic torques. One involves the use of internal models to centrally compute predicted interaction torques and their explicit compensation through anticipatory adjustment of descending motor commands. The alternative, based on the equilibrium-point hypothesis, claims that descending signals can be simple and related to the desired movement kinematics only, while spinal feedback mechanisms are responsible for the appropriate creation and coordination of dynamic muscle forces. Partial supporting evidence exists in each case. However, until now no model has explicitly shown, in the case of the second hypothesis, whether peripheral feedback is really sufficient on its own for coordinating the motion of several joints while at the same time accommodating intersegmental interaction torques. Here we propose a minimal computational model to examine this question. Using a biomechanics simulation of a two-joint arm controlled by spinal neural circuitry, we show for the first time that it is indeed possible for the neuromusculoskeletal system to transform simple descending control signals into muscle activation patterns that accommodate interaction forces depending on their direction and magnitude. This is achieved without the aid of any central predictive signal. Even though the model makes various simplifications and abstractions compared to the complexities involved in the control of human arm movements, the finding lends plausibility to the hypothesis that some multijoint movements can in principle be controlled even in the absence of internal models of intersegmental dynamics or learned compensatory motor signals.

Human Perivascular Stem Cell-Based Bone Graft Substitute Induces Rat Spinal Fusion

PubMed Central

Chung, Choon G.; James, Aaron W.; Asatrian, Greg; Chang, Le; Nguyen, Alan; Le, Khoi; Bayani, Georgina; Lee, Robert; Stoker, David; Zhang, Xinli

2014-01-01

Adipose tissue is an attractive source of mesenchymal stem cells (MSCs) because of its abundance and accessibility. We have previously defined a population of native MSCs termed perivascular stem cells (PSCs), purified from diverse human tissues, including adipose tissue. Human PSCs (hPSCs) are a bipartite cell population composed of pericytes (CD146+CD34−CD45−) and adventitial cells (CD146−CD34+CD45−), isolated by fluorescence-activated cell sorting and with properties identical to those of culture identified MSCs. Our previous studies showed that hPSCs exhibit improved bone formation compared with a sample-matched unpurified population (termed stromal vascular fraction); however, it is not known whether hPSCs would be efficacious in a spinal fusion model. To investigate, we evaluated the osteogenic potential of freshly sorted hPSCs without culture expansion and differentiation in a rat model of posterolateral lumbar spinal fusion. We compared increasing dosages of implanted hPSCs to assess for dose-dependent efficacy. All hPSC treatment groups induced successful spinal fusion, assessed by manual palpation and microcomputed tomography. Computerized biomechanical simulation (finite element analysis) further demonstrated bone fusion with hPSC treatment. Histological analyses showed robust endochondral ossification in hPSC-treated samples. Finally, we confirmed that implanted hPSCs indeed differentiated into osteoblasts and osteocytes; however, the majority of the new bone formation was of host origin. These results suggest that implanted hPSCs positively regulate bone formation via direct and paracrine mechanisms. In summary, hPSCs are a readily available MSC population that effectively forms bone without requirements for culture or predifferentiation. Thus, hPSC-based products show promise for future efforts in clinical bone regeneration and repair. PMID:25154782

Generating classes of 3D virtual mandibles for AR-based medical simulation.

PubMed

Hippalgaonkar, Neha R; Sider, Alexa D; Hamza-Lup, Felix G; Santhanam, Anand P; Jaganathan, Bala; Imielinska, Celina; Rolland, Jannick P

2008-01-01

Simulation and modeling represent promising tools for several application domains from engineering to forensic science and medicine. Advances in 3D imaging technology convey paradigms such as augmented reality (AR) and mixed reality inside promising simulation tools for the training industry. Motivated by the requirement for superimposing anatomically correct 3D models on a human patient simulator (HPS) and visualizing them in an AR environment, the purpose of this research effort was to develop and validate a method for scaling a source human mandible to a target human mandible within a 2 mm root mean square (RMS) error. Results show that, given a distance between 2 same landmarks on 2 different mandibles, a relative scaling factor may be computed. Using this scaling factor, results show that a 3D virtual mandible model can be made morphometrically equivalent to a real target-specific mandible within a 1.30 mm RMS error. The virtual mandible may be further used as a reference target for registering other anatomic models, such as the lungs, on the HPS. Such registration will be made possible by physical constraints among the mandible and the spinal column in the horizontal normal rest position.

Height increase, neuromuscular function, and back pain during 6 degrees head-down tilt with traction

NASA Technical Reports Server (NTRS)

Styf, J. R.; Ballard, R. E.; Fechner, K.; Watenpaugh, D. E.; Kahan, N. J.; Hargens, A. R.

1997-01-01

BACKGROUND: Spinal lengthening and back pain are commonly experienced by astronauts exposed to microgravity. METHODS: To develop a ground-based simulation for spinal adaptation to microgravity, we investigated height increase, neuromuscular function and back pain in 6 subjects all of whom underwent two forms of bed rest for 3 d. One form consisted of 6 degrees of head-down tilt (HDT) with balanced traction, while the other was horizontal bed rest (HBR). Subjects had a 2-week recovery period in between the studies. RESULTS: Total body and spinal length increased significantly more and the subjects had significantly more back pain during HDT with balanced traction compared to HBR. The distance between the lower endplate of L4 and upper endplate of S1, as measured by ultrasonography, increased significantly in both treatments to the same degree. Intramuscular pressures in the erector spinae muscles and ankle torque measurements during plantarflexion and dorsiflexion did not change significantly during either treatment. CONCLUSION: Compared to HBR, HDT with balanced traction may be a better method to simulate changes of total body and spinal lengths, as well as back pain seen in microgravity.

Spinal surgery: variations in health care costs and implications for episode-based bundled payments.

PubMed

Ugiliweneza, Beatrice; Kong, Maiying; Nosova, Kristin; Huang, Kevin T; Babu, Ranjith; Lad, Shivanand P; Boakye, Maxwell

2014-07-01

Retrospective, observational. To simulate what episodes of care in spinal surgery might look like in a bundled payment system and to evaluate the associated costs and characteristics. Episode-based payment bundling has received considerable attention as a potential method to help curb the rise in health care spending and is being investigated as a new payment model as part of the Affordable Care Act. Although earlier studies investigated bundled payments in a number of surgical settings, very few focused on spine surgery, specifically. We analyzed data from MarketScan. Patients were included in the study if they underwent cervical or lumbar spinal surgery during 2000-2009, had at least 2-year preoperative and 90-day postoperative follow-up data. Patients were grouped on the basis of their diagnosis-related group (DRG) and then tracked in simulated episodes-of-care/payment bundles that lasted for the duration of 30, 60, and 90 days after the discharge from the index-surgical hospitalization. The total cost associated with each episode-of-care duration was measured and characterized. A total of 196,918 patients met our inclusion criteria. Significant variation existed between DRGs, ranging from $11,180 (30-day bundle, DRG 491) to $107,642 (30-day bundle, DRG 456). There were significant cost variations within each individual DRG. Postdischarge care accounted for a relatively small portion of overall bundle costs (range, 4%-8% in 90-day bundles). Total bundle costs remained relatively flat as bundle-length increased (total average cost of 30-day bundle: $33,522 vs. $35,165 for 90-day bundle). Payments to hospitals accounted for the largest portion of bundle costs (76%). There exists significant variation in total health care costs for patients who undergo spinal surgery, even within a given DRG. Better characterization of impacts of a bundled payment system in spine surgery is important for understanding the costs of index procedure hospital, physician services, and postoperative care on potential future health care policy decision making. N/A.

Depression, mood state, and back pain during microgravity simulated by bed rest

NASA Technical Reports Server (NTRS)

Styf, J. R.; Hutchinson, K.; Carlsson, S. G.; Hargens, A. R.

2001-01-01

OBJECTIVE: The objective of this study was to develop a ground-based model for spinal adaptation to microgravity and to study the effects of spinal adaptation on depression, mood state, and pain intensity. METHODS: We investigated back pain, mood state, and depression in six subjects, all of whom were exposed to microgravity, simulated by two forms of bed rest, for 3 days. One form consisted of bed rest with 6 degrees of head-down tilt and balanced traction, and the other consisted of horizontal bed rest. Subjects had a 2-week period of recovery between the studies. The effects of bed rest on pain intensity in the lower back, depression, and mood state were investigated. RESULTS: Subjects experienced significantly more intense lower back pain, lower hemisphere abdominal pain, headache, and leg pain during head-down tilt bed rest. They had higher scores on the Beck Depression Inventory (ie, were more depressed) and significantly lower scores on the activity scale of the Bond-Lader questionnaire. CONCLUSIONS: Bed rest with 6 degrees of head-down tilt may be a better experimental model than horizontal bed rest for inducing the pain and psychosomatic reactions experienced in microgravity. Head-down tilt with balanced traction may be a useful method to induce low back pain, mood changes, and altered self-rated activity level in bed rest studies.

Computational modeling of blast wave interaction with a human body and assessment of traumatic brain injury

NASA Astrophysics Data System (ADS)

Tan, X. G.; Przekwas, A. J.; Gupta, R. K.

2017-11-01

The modeling of human body biomechanics resulting from blast exposure poses great challenges because of the complex geometry and the substantial material heterogeneity. We developed a detailed human body finite element model representing both the geometry and the materials realistically. The model includes the detailed head (face, skull, brain and spinal cord), the neck, the skeleton, air cavities (lungs) and the tissues. Hence, it can be used to properly model the stress wave propagation in the human body subjected to blast loading. The blast loading on the human was generated from a simulated C4 explosion. We used the highly scalable solvers in the multi-physics code CoBi for both the blast simulation and the human body biomechanics. The meshes generated for these simulations are of good quality so that relatively large time-step sizes can be used without resorting to artificial time scaling treatments. The coupled gas dynamics and biomechanics solutions were validated against the shock tube test data. The human body models were used to conduct parametric simulations to find the biomechanical response and the brain injury mechanism due to blasts impacting the human body. Under the same blast loading condition, we showed the importance of inclusion of the whole body.

Dynamic biomechanical examination of the lumbar spine with implanted total spinal segment replacement (TSSR) utilizing a pendulum testing system.

PubMed

Daniels, Alan H; Paller, David J; Koruprolu, Sarath; Palumbo, Mark A; Crisco, Joseph J

2013-01-01

Biomechanical investigations of spinal motion preserving implants help in the understanding of their in vivo behavior. In this study, we hypothesized that the lumbar spine with implanted total spinal segment replacement (TSSR) would exhibit decreased dynamic stiffness and more rapid energy absorption compared to native functional spinal units under simulated physiologic motion when tested with the pendulum system. Five unembalmed, frozen human lumbar functional spinal units were tested on the pendulum system with axial compressive loads of 181 N, 282 N, 385 N, and 488 N before and after Flexuspine total spinal segment replacement implantation. Testing in flexion, extension, and lateral bending began by rotating the pendulum to 5°; resulting in unconstrained oscillatory motion. The number of rotations to equilibrium was recorded and bending stiffness (N-m/°) was calculated and compared for each testing mode. The total spinal segment replacement reached equilibrium with significantly fewer cycles to equilibrium compared to the intact functional spinal unit at all loads in flexion (p<0.011), and at loads of 385 N and 488 N in lateral bending (p<0.020). Mean bending stiffness in flexion, extension, and lateral bending increased with increasing load for both the intact functional spinal unit and total spinal segment replacement constructs (p<0.001), with no significant differences in stiffness between the intact functional spinal unit and total spinal segment replacement in any of the test modes (p>0.18). Lumbar functional spinal units with implanted total spinal segment replacement were found to have similar dynamic bending stiffness, but absorbed energy at a more rapid rate than intact functional spinal units during cyclic loading with an unconstrained pendulum system. Although the effects on clinical performance of motion preserving devices is not fully known, these results provide further insight into the biomechanical behavior of this device under approximated physiologic loading conditions.

Dynamic Biomechanical Examination of the Lumbar Spine with Implanted Total Spinal Segment Replacement (TSSR) Utilizing a Pendulum Testing System

PubMed Central

Daniels, Alan H.; Paller, David J.; Koruprolu, Sarath; Palumbo, Mark A.; Crisco, Joseph J.

2013-01-01

Background Biomechanical investigations of spinal motion preserving implants help in the understanding of their in vivo behavior. In this study, we hypothesized that the lumbar spine with implanted total spinal segment replacement (TSSR) would exhibit decreased dynamic stiffness and more rapid energy absorption compared to native functional spinal units under simulated physiologic motion when tested with the pendulum system. Methods Five unembalmed, frozen human lumbar functional spinal units were tested on the pendulum system with axial compressive loads of 181 N, 282 N, 385 N, and 488 N before and after Flexuspine total spinal segment replacement implantation. Testing in flexion, extension, and lateral bending began by rotating the pendulum to 5°; resulting in unconstrained oscillatory motion. The number of rotations to equilibrium was recorded and bending stiffness (N-m/°) was calculated and compared for each testing mode. Results The total spinal segment replacement reached equilibrium with significantly fewer cycles to equilibrium compared to the intact functional spinal unit at all loads in flexion (p<0.011), and at loads of 385 N and 488 N in lateral bending (p<0.020). Mean bending stiffness in flexion, extension, and lateral bending increased with increasing load for both the intact functional spinal unit and total spinal segment replacement constructs (p<0.001), with no significant differences in stiffness between the intact functional spinal unit and total spinal segment replacement in any of the test modes (p>0.18). Conclusions Lumbar functional spinal units with implanted total spinal segment replacement were found to have similar dynamic bending stiffness, but absorbed energy at a more rapid rate than intact functional spinal units during cyclic loading with an unconstrained pendulum system. Although the effects on clinical performance of motion preserving devices is not fully known, these results provide further insight into the biomechanical behavior of this device under approximated physiologic loading conditions. PMID:23451222

SU-E-T-255: Optimized Supine Craniospinal Irradiation with Image-Guided and Field Matched Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Z; Holupka, E; Naughton, J

2014-06-01

Purpose: Conventional craniospinal irradiation (CSI) challenges include dose inhomogeneity at field junctions and position uncertainty due to the field divergence, particular for the two spinal fields. Here we outline a new supine CSI technique to address these difficulties. Methods: Patient was simulated in supine position. The cranial fields had isocenter at C2/C3 vertebral and were matched with 1st spinal field. Their inferior border was chosen to avoid the shoulder, as well as chin from the 1st spine field. Their collimator angles were dependent on asymmetry jaw setting of the 1st spinal field. With couch rotation, the spinal field gantry anglesmore » were adjusted to ensure, the inferior border of 1st and superior border of 2nd spinal fields were perpendicular to the table top. The radio-opaque wire position for the spinal junction was located initially by the light field from an anterior setup beam, and was finalized by the portal imaging of the 1st spinal field. With reference to the spinal junction wire, the fields were matched by positioning the isocenter of the 2nd spinal field. A formula was derived to optimize supine CSI treatment planning, by utilizing the relationship among the Yjaw setting, the spinal field gantry angles, cranial field collimator angles, and the spinal field isocenters location. The plan was delivered with portal imaging alignment for the both cranial and spinal junctions. Results: Utilizing this technique with matching beams, and conventional technique such as feathering and forwarding planning, a homogenous dose distribution was achieved throughout the entire CSI treatment volume including the spinal junction. Placing the spinal junction wire visualized in both spinal portals, allows for precise determination and verification of the appropriate match line of the spine fields. Conclusion: This technique of optimization supine CSI achieved a homogenous dose distributions and patient localization accuracy with image-guided and matched beams.« less

[A new two-chamber model for examination and demonstration of transdural fluid leakage after spinal anesthesia].

PubMed

Enk, D; Enk, E

1995-11-01

Various in vitro models have been introduced for comparative examinations of post-dural-puncture trauma and measurement of liquor leakage through puncture sites. These models allow simulation of subarachnoid, but not of peridural, pressure. A new two-chamber-model realizes the simulation of both subarachnoid and peridural pressure and allows observation of in vitro punctures with video-documentation. Frame grabbing and (computer-aided) image analysis show new aspects of spinal puncture effects. Therefore, post-dural-puncture trauma and retraction can be objectively visualized by this method, which has not previously been demonstrated. Two-chamber-model consists of two short aluminium cylinders. Native human dura patches (8X8 mm) from fresh cadavers are put (correctly oriented) between two special polyamide seals. Mounted between the upper and lower cylinder, these seals stretch the dura patch, which remains flexible and even in all directions. After filling of the lower (subarachnoid) and upper (peridural) chamber with Ringer lactate solution, positive or negative physiological pressure can be adjusted by way of two (Ringer lactate solution filled) infusion lines in each chamber. Puncturing is performed at an angle of 57 degrees to the dura. The model allows examination with epi-illumination and transmitted (polarized) light. In vitro punctures are observed through an inverted camera lens with an CCD-Hi8 video camera (Canon UC1HI) looking into the peridural chamber and documented by means of an S-VHS video recorder (Panasonic NV-FS200EG). After true-colour frame grabbing by a video digitizer (Fast Screen Machine II), single video frames can be optimized and analysed with a 486-66 MHz computer and conventional software (Corel Draw 3.0, Photostyler 1.1a, DDL Aequitas 1.00b). Punctures demonstrated in this paper have been done under simulation of a transdural gradient of 20 cm water similar to the situation of a recumbent patient (15 cm water in the subarachnoid and -5 cm water in the peridural chamber). The punctures were followed by short-time observation for up to 10 minutes. By making it possible to obtains a picture of the puncture site at 20-ms intervals (because of the PAL norm of 50 half-frames/s), video-documentation has become accepted as superior to conventional photography. When the Ringer lactate solution in the subarachnoid chamber is stained with methylene blue, transdural leakage can easily be observed. The result of this documentation technique demonstrate that not dural puncture can be atraumatic, when a 29-G Quincke needle is used. Calculation on the difference between a digitized video frame before and after the puncture clearly illustrates the dural trauma. Owing to their non-cutting tip, as expected, pencil-point needles leave diffuse changes across the dura patch, whereas a more local trauma was observed after puncturing with cutting-tip needles. The same computer calculation between two video frames allows examination of post-puncture-dural retraction of the puncture site. In this connection, we found that relevant dural retraction is a phenomenon limited to the first minute after puncture. Thin spinal needles with so-called modern tips (e.g. Whitacre, Atraucan) can minimize the post-dural-puncture trauma, whereas thicker, conventional, spinal needles (Quincke) leave considerable dural defects. The two-chamber-model presented allows easy simulation of physiological subarachnoid and peridural pressure. The Ringer lactate solution in the subarachnoid chamber corresponds to the liquor, whereas that in the peridural chamber corresponds to the intercellular (peridural) space. The tension of the dural patch between the polyamide seals is similar to the situation in an anotomical model observed by spinaloscopy (in an earlier study). With the video documentation and computer-aided analysis technique introduced, dural trauma and retraction of the puncture site can be examined and demo

A kinematic model to assess spinal motion during walking.

PubMed

Konz, Regina J; Fatone, Stefania; Stine, Rebecca L; Ganju, Aruna; Gard, Steven A; Ondra, Stephen L

2006-11-15

A 3-dimensional multi-segment kinematic spine model was developed for noninvasive analysis of spinal motion during walking. Preliminary data from able-bodied ambulators were collected and analyzed using the model. Neither the spine's role during walking nor the effect of surgical spinal stabilization on gait is fully understood. Typically, gait analysis models disregard the spine entirely or regard it as a single rigid structure. Data on regional spinal movements, in conjunction with lower limb data, associated with walking are scarce. KinTrak software (Motion Analysis Corp., Santa Rosa, CA) was used to create a biomechanical model for analysis of 3-dimensional regional spinal movements. Measuring known angles from a mechanical model and comparing them to the calculated angles validated the kinematic model. Spine motion data were collected from 10 able-bodied adults walking at 5 self-selected speeds. These results were compared to data reported in the literature. The uniaxial angles measured on the mechanical model were within 5 degrees of the calculated kinematic model angles, and the coupled angles were within 2 degrees. Regional spine kinematics from able-bodied subjects calculated with this model compared well to data reported by other authors. A multi-segment kinematic spine model has been developed and validated for analysis of spinal motion during walking. By understanding the spine's role during ambulation and the cause-and-effect relationship between spine motion and lower limb motion, preoperative planning may be augmented to restore normal alignment and balance with minimal negative effects on walking.

[APPLICATION OF THREE DIMENSIONAL PRINTING ON MANUFACTURING BIONIC SCAFFOLDS OF SPINAL CORD IN RATS].

PubMed

Chen, Yisheng; Wang, Jingjing; Chen, Xuyi; Chen, Chong; Tu, Yue; Zhang, Sai; Li, Xiaohong

2015-03-01

To fabricate the bionic scaffolds of rat spinal cord by combining three dimensional (3D) printer and 3D software, so as to lay the foundation of theory and technology for the manufacture of scaffolds by using biomaterials. Three female Sprague Dawley rats were scanned by 7.0T MRI to obtain the shape and position data of the cross section and gray matter of T8 to T10 spinal cord. Combined with data of position and shape of nerve conduction beam, the relevant data were obtained via Getdata software. Then the 3D graphics were made and converted to stereolithography (STL) format by using SolidWorks software. Photosensitive resin was used as the materials of spinal cord scaffolds. The bionic scaffolds were fabricated by 3D printer. MRI showed that the section shape of T8 to T10 segments of the spinal cord were approximately oval with a relatively long sagittal diameter of (2.20 ± 0.52) mm and short transverse diameter of (2.05 ± 0.24) mm, and the data of nerve conduction bundle were featured in the STL format. The spinal cord bionic scaffolds of the target segments made by 3D printer were similar to the spinal cord of rat in the morphology and size, and the position of pores simulated normal nerve conduction of rat spinal cord. Spinal cord scaffolds produced by 3D printer which have similar shape and size of normal rat spinal cord are more bionic, and the procedure is simple. This technology combined with biomaterials is also promising in spinal cord repairing after spinal cord injury.

Coordination of Fictive Motor Activity in the Larval Zebrafish Is Generated by Non-Segmental Mechanisms

PubMed Central

Wiggin, Timothy D.; Peck, Jack H.; Masino, Mark A.

2014-01-01

The cellular and network basis for most vertebrate locomotor central pattern generators (CPGs) is incompletely characterized, but organizational models based on known CPG architectures have been proposed. Segmental models propose that each spinal segment contains a circuit that controls local coordination and sends longer projections to coordinate activity between segments. Unsegmented/continuous models propose that patterned motor output is driven by gradients of neurons and synapses that do not have segmental boundaries. We tested these ideas in the larval zebrafish, an animal that swims in discrete episodes, each of which is composed of coordinated motor bursts that progress rostrocaudally and alternate from side to side. We perturbed the spinal cord using spinal transections or strychnine application and measured the effect on fictive motor output. Spinal transections eliminated episode structure, and reduced both rostrocaudal and side-to-side coordination. Preparations with fewer intact segments were more severely affected, and preparations consisting of midbody and caudal segments were more severely affected than those consisting of rostral segments. In reduced preparations with the same number of intact spinal segments, side-to-side coordination was more severely disrupted than rostrocaudal coordination. Reducing glycine receptor signaling with strychnine reversibly disrupted both rostrocaudal and side-to-side coordination in spinalized larvae without disrupting episodic structure. Both spinal transection and strychnine decreased the stability of the motor rhythm, but this effect was not causal in reducing coordination. These results are inconsistent with a segmented model of the spinal cord and are better explained by a continuous model in which motor neuron coordination is controlled by segment-spanning microcircuits. PMID:25275377

Recapitulation of spinal motor neuron-specific disease phenotypes in a human cell model of spinal muscular atrophy

PubMed Central

Wang, Zhi-Bo; Zhang, Xiaoqing; Li, Xue-Jun

2013-01-01

Establishing human cell models of spinal muscular atrophy (SMA) to mimic motor neuron-specific phenotypes holds the key to understanding the pathogenesis of this devastating disease. Here, we developed a closely representative cell model of SMA by knocking down the disease-determining gene, survival motor neuron (SMN), in human embryonic stem cells (hESCs). Our study with this cell model demonstrated that knocking down of SMN does not interfere with neural induction or the initial specification of spinal motor neurons. Notably, the axonal outgrowth of spinal motor neurons was significantly impaired and these disease-mimicking neurons subsequently degenerated. Furthermore, these disease phenotypes were caused by SMN-full length (SMN-FL) but not SMN-Δ7 (lacking exon 7) knockdown, and were specific to spinal motor neurons. Restoring the expression of SMN-FL completely ameliorated all of the disease phenotypes, including specific axonal defects and motor neuron loss. Finally, knockdown of SMN-FL led to excessive mitochondrial oxidative stress in human motor neuron progenitors. The involvement of oxidative stress in the degeneration of spinal motor neurons in the SMA cell model was further confirmed by the administration of N-acetylcysteine, a potent antioxidant, which prevented disease-related apoptosis and subsequent motor neuron death. Thus, we report here the successful establishment of an hESC-based SMA model, which exhibits disease gene isoform specificity, cell type specificity, and phenotype reversibility. Our model provides a unique paradigm for studying how motor neurons specifically degenerate and highlights the potential importance of antioxidants for the treatment of SMA. PMID:23208423

Hybrid Equation/Agent-Based Model of Ischemia-Induced Hyperemia and Pressure Ulcer Formation Predicts Greater Propensity to Ulcerate in Subjects with Spinal Cord Injury

PubMed Central

Solovyev, Alexey; Mi, Qi; Tzen, Yi-Ting; Brienza, David; Vodovotz, Yoram

2013-01-01

Pressure ulcers are costly and life-threatening complications for people with spinal cord injury (SCI). People with SCI also exhibit differential blood flow properties in non-ulcerated skin. We hypothesized that a computer simulation of the pressure ulcer formation process, informed by data regarding skin blood flow and reactive hyperemia in response to pressure, could provide insights into the pathogenesis and effective treatment of post-SCI pressure ulcers. Agent-Based Models (ABM) are useful in settings such as pressure ulcers, in which spatial realism is important. Ordinary Differential Equation-based (ODE) models are useful when modeling physiological phenomena such as reactive hyperemia. Accordingly, we constructed a hybrid model that combines ODEs related to blood flow along with an ABM of skin injury, inflammation, and ulcer formation. The relationship between pressure and the course of ulcer formation, as well as several other important characteristic patterns of pressure ulcer formation, was demonstrated in this model. The ODE portion of this model was calibrated to data related to blood flow following experimental pressure responses in non-injured human subjects or to data from people with SCI. This model predicted a higher propensity to form ulcers in response to pressure in people with SCI vs. non-injured control subjects, and thus may serve as novel diagnostic platform for post-SCI ulcer formation. PMID:23696726

Comparison of Spinal Needle Deflection in a Ballistic Gel Model.

PubMed

Rand, Ethan; Christolias, George; Visco, Christopher; R Singh, Jaspal

2016-10-01

Percutaneous diagnostic and therapeutic procedures are commonly used in the treatment of spinal pain. The success of these procedures depends on the accuracy of needle placement, which is influenced by needle size and shape. The purpose of this study is to examine and quantify the deviation of commonly used spinal needles based on needle tip design and gauge, using a ballistic gel tissue simulant. Six needles commonly used in spinal procedures (Quincke, Short Bevel, Chiba, Tuohy, Hustead, Whitacre) were selected for use in this study. Ballistic gel samples were made in molds of two depths, 40mm and 80 mm. Each needle was mounted in a drill press to ensure an accurate needle trajectory. Distance of deflection was recorded for each needle. In comparing the mean deflection of 22 gauge needles of all types at 80 mm of depth, deflection was greatest among beveled needles [Short Bevel (9.96 ± 0.77 mm), Quincke (8.89 ± 0.17 mm), Chiba (7.71 ± 1.16 mm)], moderate among epidural needles [Tuohy (7.64 ± 0.16 mm) and least among the pencil-point needles [Whitacre (0.73 ± 0.34 mm)]. Increased gauge (25 g) led to a significant increase in deflection among beveled needles. The direction of deflection was away from the bevel with Quincke, Chiba and Short Beveled needles and toward the bevel of the Tuohy and Hustead needles. Deflection of the Whitacre pencil-point needle was minimal. There is clinical utility in knowing the relative deflection of various needle tips. When a procedure requires a needle to be steered around obstacles, or along non-collinear targets, the predictable and large amount of deflection obtained through use of a beveled spinal needle may prove beneficial.

Comparison of Spinal Needle Deflection in a Ballistic Gel Model

PubMed Central

Rand, Ethan; Christolias, George; Visco, Christopher; R. Singh, Jaspal

2016-01-01

Background Percutaneous diagnostic and therapeutic procedures are commonly used in the treatment of spinal pain. The success of these procedures depends on the accuracy of needle placement, which is influenced by needle size and shape. Objectives The purpose of this study is to examine and quantify the deviation of commonly used spinal needles based on needle tip design and gauge, using a ballistic gel tissue simulant. Materials and Methods Six needles commonly used in spinal procedures (Quincke, Short Bevel, Chiba, Tuohy, Hustead, Whitacre) were selected for use in this study. Ballistic gel samples were made in molds of two depths, 40mm and 80 mm. Each needle was mounted in a drill press to ensure an accurate needle trajectory. Distance of deflection was recorded for each needle. Results In comparing the mean deflection of 22 gauge needles of all types at 80 mm of depth, deflection was greatest among beveled needles [Short Bevel (9.96 ± 0.77 mm), Quincke (8.89 ± 0.17 mm), Chiba (7.71 ± 1.16 mm)], moderate among epidural needles [Tuohy (7.64 ± 0.16 mm) and least among the pencil-point needles [Whitacre (0.73 ± 0.34 mm)]. Increased gauge (25 g) led to a significant increase in deflection among beveled needles. The direction of deflection was away from the bevel with Quincke, Chiba and Short Beveled needles and toward the bevel of the Tuohy and Hustead needles. Deflection of the Whitacre pencil-point needle was minimal. Conclusions There is clinical utility in knowing the relative deflection of various needle tips. When a procedure requires a needle to be steered around obstacles, or along non-collinear targets, the predictable and large amount of deflection obtained through use of a beveled spinal needle may prove beneficial. PMID:27847693

Effects of inter-individual lumbar spine geometry variation on load-sharing: Geometrically personalized Finite Element study.

PubMed

Naserkhaki, Sadegh; Jaremko, Jacob L; El-Rich, Marwan

2016-09-06

There is a large, at times contradictory, body of research relating spinal curvature to Low Back Pain (LBP). Mechanical load is considered as important factor in LBP etiology. Geometry of the spinal structures and sagittal curvature of the lumbar spine govern its mechanical behavior. Thus, understanding how inter-individual geometry particularly sagittal curvature variation affects the spinal load-sharing becomes of high importance in LBP assessment. This study calculated and compared kinematics and load-sharing in three ligamentous lumbosacral spines: one hypo-lordotic (Hypo-L) with low lordosis, one normal-lordotic (Norm-L) with normal lordosis, and one hyper-lordotic (Hyper-L) with high lordosis in flexed and extended postures using 3D nonlinear Finite Element (FE) modeling. These postures were simulated by applying Follower Load (FL) combined with flexion or extension moment. The Hypo-L spine demonstrated stiffer behavior in flexion but more flexible response to extension compared to the Norm-L spine. The excessive lordosis stiffened response of the Hyper-L spine to extension but did not affect its resistance to flexion compared to the Norm-L spine. Despite the different resisting actions of the posterior ligaments to flexion moment, the increase of disc compression was similar in all the spines leading to similar load-sharing. However, resistance of the facet joints to extension was more important in the Norm- and Hyper-L spines which reduced the disc compression. The spinal curvature strongly influenced the magnitude and location of load on the spinal components and also altered the kinematics and load-sharing particularly in extension. Consideration of the subject-specific geometry and sagittal curvature should be an integral part of mechanical analysis of the lumbar spine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modelling of the optimal bupivacaine dose for spinal anaesthesia in ambulatory surgery based on data from systematic review.

PubMed

Lemoine, Adrien; Mazoit, Jean X; Bonnet, Francis

2016-11-01

Spinal bupivacaine is used for day-case surgery but the appropriate dose that guarantees hospital discharge is unknown. We sought to determine the spinal bupivacaine dose that prevents delayed hospital discharge in ambulatory surgery. Systematic review of clinical trials. Comprehensive search in electronic databases of studies published between 1996 and 2014 reporting the use of spinal bupivacaine in ambulatory patients. Additional articles were retrieved through hyperlinks and by manually searching reference lists in original articles, review articles and correspondence published in English and French. Data were used to calculate, motor block duration and discharge time, an estimated maximal effect (Emax: maximum theoretical time of motor block) and the effective dose to obtain half of Emax (D50) with 95% confidence intervals (CIs). A simulation was performed to determine the dose corresponding to a time to recovery of 300 min for motor function, and 360 min for discharge, in 95% of the patients. In total, 23 studies (1062 patients) were included for analysis of the time to recovery of motor function, and 12 studies (618 patients) for the time to hospital discharge. The Emax for recovery of motor function was 268 min [95% CI (189 to 433 min)] and the D50 was 3.9 mg [95% CI (2.3 to 6.2 mg)]. A 7.5-mg dose of bupivacaine enables resolution of motor block and ambulation within 300 min in 95% of the patients. A 5-mg dose or less was associated with an unacceptable failure rate. Ambulatory surgery is possible under spinal anaesthesia with bupivacaine although the dose range that ensures reliable anaesthesia with duration short enough to guarantee ambulatory management is narrow.

Mechanisms of spinal motoneurons survival in rats under simulated hypogravity on earth

NASA Astrophysics Data System (ADS)

Islamov, R. R.; Mishagina, E. A.; Tyapkina, O. V.; Shajmardanova, G. F.; Eremeev, A. A.; Kozlovskaya, I. B.; Nikolskij, E. E.; Grigorjev, A. I.

2011-05-01

It was previously shown that different cell types in vivo and in vitro may die via apoptosis under weightlessness conditions in space as well as in simulated hypogravity on the Earth. We assessed survivability of spinal motoneurons of rats after 35-day antiorthostatic hind limb suspension. Following weight bearing, unloading the total protein content in lumbar spinal cord is dropped by 21%. The electrophysiological studies of m. gastrocnemius revealed an elevated motoneurons' reflex excitability and conduction disturbances in the sciatic nerve axons. The number of myelinated fibers in the ventral root of experimental animals was insignificantly increased by 35-day of antiorthostatic hind limb suspension, although the retrograde axonal transport was significantly decreased during the first week of simulated hypogravity. The results of the immunohistochemical assay with antibodies against proapoptotic protein caspase 9 and cytotoxicity marker neuron specific nitric oxide synthase (nNOS) and the TUNEL staining did not reveal any signs of apoptosis in motoneurons of suspended and control animals. To examine the possible adaptation mechanisms activated in motoneurons in response to simulated hypogravity we investigated immunoexpression of Hsp25 and Hsp70 in lumbar spinal cord of the rats after 35-day antiorthostatic hind limb suspension. Comparative analysis of the immunohistochemical reaction with anti-Hsp25 antibodies revealed differential staining of motoneurons in intact and experimental animals. The density of immunoprecipitate with anti-Hsp25 antibodies was substantially higher in motoneurons of the 35-day suspended than control rats and the more intensive precipitate in this reaction was observed in motoneuron neuritis. Quantitative analysis of Hsp25 expression demonstrated an increase in the Hsp25 level by 95% in experimental rats compared to the control. The immunoexpression of Hsp70 found no qualitative and quantitative differences in control and experimental lumbar spinal cords. Taken together our results show that (1) rat motoneurons survived after 35-day antiorthostatic hind limb suspension and the changes in neurons had a mostly functional character, and (2) the increased immunoexpression of Hsp25 can be considered as the anti-apoptotic factor.

Spinal Anesthesia in Infant Rats: Development of a Model and Assessment of Neurological Outcomes

PubMed Central

Yahalom, Barak; Athiraman, Umeshkumar; Soriano, Sulpicio G.; Zurakowski, David; Carpino, Elizabeth; Corfas, Gabriel; Berde, Charles B.

2012-01-01

Background Previous studies in infant rats and case-control studies of human infants undergoing surgery have raised concerns about potential neurodevelopmental toxicities of general anesthesia. Spinal anesthesia is an alternative to general anesthesia for some infant surgeries. To test for potential toxicity, we developed a spinal anesthesia model in infant rats. Methods Rats of postnatal ages 7, 14, and 21 days were assigned to: no treatment; 1% isoflurane for either 1 h or 6 h, or lumbar spinal injection of saline or bupivacaine, at doses of 3.75 mg/kg (low dose) or 7.5 mg/kg (high dose). Subgroups of animals underwent neurobehavioral testing and blood gas analysis. Brain and lumbar spinal cord sections were examined for apoptosis using cleaved caspase-3 immunostaining. Lumbar spinal cord was examined histologically. Rats exposed to spinal or general anesthesia as infants underwent Rotarod testing of motor performance as adults. Data were analyzed using analysis of variance (ANOVA) using general linear models, Friedman Tests, and Mann–Whitney U tests, as appropriate. Results Bupivacaine 3.75 mg/kg was effective for spinal anesthesia in all age groups, and produced sensory and motor function recovered in 40 to 60 min. Blood gases were similar among groups. Brain and spinal cord apoptosis increased in rats receiving 6 h of 1% isoflurane, but not among the other treatments. All groups showed intact motor performance at adulthood. Conclusions Spinal anesthesia is technically feasible in infant rats, and appears benign in terms of neuroapoptotic and neuromotor sequelae. PMID:21555934

Global geometric torsion estimation in adolescent idiopathic scoliosis.

PubMed

Kadoury, Samuel; Shen, Jesse; Parent, Stefan

2014-04-01

Several attempts have been made to measure geometrical torsion in adolescent idiopathic scoliosis (AIS) and quantify the three-dimensional (3D) deformation of the spine. However, these approaches are sensitive to imprecisions in the 3D modeling of the anatomy and can only capture the effect locally at the vertebrae, ignoring the global effect at the regional level and thus have never been widely used to follow the progression of a deformity. The goal of this work was to evaluate the relevance of a novel geometric torsion descriptor based on a parametric modeling of the spinal curve as a 3D index of scoliosis. First, an image-based approach anchored on prior statistical distributions is used to reconstruct the spine in 3D from biplanar X-rays. Geometric torsion measuring the twisting effect of the spine is then estimated using a technique that approximates local arc-lengths with parametric curve fitting centered at the neutral vertebra in different spinal regions. We first evaluated the method with simulated experiments, demonstrating the method's robustness toward added noise and reconstruction inaccuracies. A pilot study involving 65 scoliotic patients exhibiting different types of deformities was also conducted. Results show the method is able to discriminate between different types of deformation based on this novel 3D index evaluated in the main thoracic and thoracolumbar/lumbar regions. This demonstrates that geometric torsion modeled by parametric spinal curve fitting is a robust tool that can be used to quantify the 3D deformation of AIS and possibly exploited as an index to classify the 3D shape.

Chiari malformation may increase perivascular cerebrospinal fluid flow into the spinal cord: A subject-specific computational modelling study.

PubMed

Lloyd, Robert A; Fletcher, David F; Clarke, Elizabeth C; Bilston, Lynne E

2017-12-08

Syringomyelia is associated with Chiari I malformation, although the mechanistic link is unclear. Studies have suggested that cerebrospinal fluid enters the spinal cord via the perivascular spaces, and that changes in the timing of the subarachnoid pressures may increase flow into the spinal cord. This study aims to determine how Chiari malformation and syringomyelia alter the subarachnoid space pressures and hence perivascular flow. Subject-specific models of healthy controls (N = 9), Chiari patients with (N = 7) and without (N = 8) syringomyelia, were developed from magnetic resonance imaging (MRI), to simulate the subarachnoid pressures. These pressures were input to an idealised model of the perivascular space to evaluate potential differences in perivascular flow. Peak pressures in Chiari patients without a syrinx were higher than in controls (46% increase; p = .029) and arrived earlier in the cardiac cycle than both controls (2.58% earlier; p = .045) and syrinx patients (2.85% earlier; p = .045). The perivascular model predicted Chiari patients without a syrinx would have the greatest flow into the cord (p < .05) if the arterial pulse delay was between 4 and 10% of the cardiac cycle. Using phase-contrast MRI the mean arterial delay for all subjects was similar, and was estimated as 4.7 ± 0.2%. The perivascular pumping rate showed a strong positive correlation (R Adj 2 =0.85; p < .0001) with extended periods of high pressure that arrived earlier in the cardiac cycle, suggesting these pressure characteristics may play a role in syrinx development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Regression models for predicting peak and continuous three-dimensional spinal loads during symmetric and asymmetric lifting tasks.

PubMed

Fathallah, F A; Marras, W S; Parnianpour, M

1999-09-01

Most biomechanical assessments of spinal loading during industrial work have focused on estimating peak spinal compressive forces under static and sagittally symmetric conditions. The main objective of this study was to explore the potential of feasibly predicting three-dimensional (3D) spinal loading in industry from various combinations of trunk kinematics, kinetics, and subject-load characteristics. The study used spinal loading, predicted by a validated electromyography-assisted model, from 11 male participants who performed a series of symmetric and asymmetric lifts. Three classes of models were developed: (a) models using workplace, subject, and trunk motion parameters as independent variables (kinematic models); (b) models using workplace, subject, and measured moments variables (kinetic models); and (c) models incorporating workplace, subject, trunk motion, and measured moments variables (combined models). The results showed that peak 3D spinal loading during symmetric and asymmetric lifting were predicted equally well using all three types of regression models. Continuous 3D loading was predicted best using the combined models. When the use of such models is infeasible, the kinematic models can provide adequate predictions. Finally, lateral shear forces (peak and continuous) were consistently underestimated using all three types of models. The study demonstrated the feasibility of predicting 3D loads on the spine under specific symmetric and asymmetric lifting tasks without the need for collecting EMG information. However, further validation and development of the models should be conducted to assess and extend their applicability to lifting conditions other than those presented in this study. Actual or potential applications of this research include exposure assessment in epidemiological studies, ergonomic intervention, and laboratory task assessment.

An animal model of functional electrical stimulation: evidence that the central nervous system modulates the consequences of training

PubMed Central

Hook, MA; Grau, JW

2011-01-01

Study Design Review of how spinal neurons can modulate the consequences of functional electrical stimulation (FES) in an animal model. Methods Spinal effects of FES are examined in male Sprague–Dawley rats transected at the second thoracic vertebra. The rats are exposed to FES training 24–48 h after surgery. Experimental manipulations of stimulation parameters, combined with physiological and pharmacological procedures, are used to examine the potential role of spinal neurons. Results The isolated spinal cord is inherently capable of learning the response–outcome relations imposed in FES training contingencies. Adaptive behavioral modifications are observed when an outcome (electrical stimulation) is contingent on a behavioral response. In contrast, a lack of correlation between the response and outcome in training produces a learning deficit in the spinal cord, rendering it incapable of adaptive learning for up to 48 h. The N-methyl-D-aspartic acid receptor appears to mediate both the adaptive plasticity and loss of plasticity, seen in this spinal model. Conclusion The behavioral effects observed with FES therapies are not simply due to the direct (motor) consequences of stimulation elicited by the activation of efferent motor neurons and/or selected muscles. FES training has the capacity to shape inherent spinal circuits and to produce a long-lasting behavioral modification. Further understanding of the spinal mechanisms underlying adaptive behavioral modification will be integral for establishing functional neural connections in a regenerating spinal system. PMID:17700514

Comparison of 4D Phase-Contrast MRI Flow Measurements to Computational Fluid Dynamics Simulations of Cerebrospinal Fluid Motion in the Cervical Spine

PubMed Central

Yiallourou, Theresia I.; Kröger, Jan Robert; Stergiopulos, Nikolaos; Maintz, David

2012-01-01

Cerebrospinal fluid (CSF) dynamics in the cervical spinal subarachnoid space (SSS) have been thought to be important to help diagnose and assess craniospinal disorders such as Chiari I malformation (CM). In this study we obtained time-resolved three directional velocity encoded phase-contrast MRI (4D PC MRI) in three healthy volunteers and four CM patients and compared the 4D PC MRI measurements to subject-specific 3D computational fluid dynamics (CFD) simulations. The CFD simulations considered the geometry to be rigid-walled and did not include small anatomical structures such as nerve roots, denticulate ligaments and arachnoid trabeculae. Results were compared at nine axial planes along the cervical SSS in terms of peak CSF velocities in both the cranial and caudal direction and visual interpretation of thru-plane velocity profiles. 4D PC MRI peak CSF velocities were consistently greater than the CFD peak velocities and these differences were more pronounced in CM patients than in healthy subjects. In the upper cervical SSS of CM patients the 4D PC MRI quantified stronger fluid jets than the CFD. Visual interpretation of the 4D PC MRI thru-plane velocity profiles showed greater pulsatile movement of CSF in the anterior SSS in comparison to the posterior and reduction in local CSF velocities near nerve roots. CFD velocity profiles were relatively uniform around the spinal cord for all subjects. This study represents the first comparison of 4D PC MRI measurements to CFD of CSF flow in the cervical SSS. The results highlight the utility of 4D PC MRI for evaluation of complex CSF dynamics and the need for improvement of CFD methodology. Future studies are needed to investigate whether integration of fine anatomical structures and gross motion of the brain and/or spinal cord into the computational model will lead to a better agreement between the two techniques. PMID:23284970

WE-AB-207B-10: On Spinal Nerve Toxicity from Single-Session SAbR in Pigs and the Translation of Small Animal NTCP Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hrycushko, B; Medin, P

Purpose: The incidence of peripheral neuropathy has risen with increased utilization of SAbR. There is no consensus regarding the dose-tolerance of the peripheral nervous system. In 2015, we commenced an investigation to test the hypotheses that single-session irradiation to the pig spinal nerves exhibit a similar dose-tolerance as that of the spinal cord and that a dose-length effect exists. This work evaluates the direct application of small animal NTCP models to both large animal spinal cord and preliminary peripheral nerve data. Methods: To date, 16 of 25 Yucatan minipigs have received single-session SAbR to a 1.5cm length and 4 ofmore » 25 have received irradiation to a 0.5cm length of left-sided C6-C8 spinal nerves. Toxicity related gait change has been observed in 13 animals (9 from the long length group and 4 from the short). This preliminary data is overlaid on several dose-response models which have been fit to rodent spinal cord tolerance experiments. Model parameters define a toxicity profile between a completely serial or parallel behaving organ. Adequacy of model application, including how length effects are handled, to published minipig spinal cord dose-response data and to preliminary peripheral nerve response data was evaluated through residual analysis. Results: No rodent-derived dose-response models were directly applicable to all pig data for the different lengths irradiated. Several models fit the long-length irradiated spinal cord data well, with the more serial-like models fitting best. Preliminary data on the short-length irradiation suggests no length effect exists, disproving our hypothesis. Conclusion: Direct application of small-animal NTCP models to pig data suggests dose-length effect predictions from small animal data may not translate clinically. However, the small animal models used have not considered dose heterogeneity and it is expected that including the low-to-mid dose levels in the penumbral region will improve this match. This work was funded by the Cancer Prevention Research Institute of Texas (CPRIT).« less

Clinical application of computer-designed polystyrene models in complex severe spinal deformities: a pilot study

PubMed Central

Mao, Keya; Xiao, Songhua; Liu, Zhengsheng; Zhang, Yonggang; Zhang, Xuesong; Wang, Zheng; Lu, Ning; Shourong, Zhu; Xifeng, Zhang; Geng, Cui; Baowei, Liu

2010-01-01

Surgical treatment of complex severe spinal deformity, involving a scoliosis Cobb angle of more than 90° and kyphosis or vertebral and rib deformity, is challenging. Preoperative two-dimensional images resulting from plain film radiography, computed tomography (CT) and magnetic resonance imaging provide limited morphometric information. Although the three-dimensional (3D) reconstruction CT with special software can view the stereo and rotate the spinal image on the screen, it cannot show the full-scale spine and cannot directly be used on the operation table. This study was conducted to investigate the application of computer-designed polystyrene models in the treatment of complex severe spinal deformity. The study involved 16 cases of complex severe spinal deformity treated in our hospital between 1 May 2004 and 31 December 2007; the mean ± SD preoperative scoliosis Cobb angle was 118° ± 27°. The CT scanning digital imaging and communication in medicine (DICOM) data sets of the affected spinal segments were collected for 3D digital reconstruction and rapid prototyping to prepare computer-designed polystyrene models, which were applied in the treatment of these cases. The computer-designed polystyrene models allowed 3D observation and measurement of the deformities directly, which helped the surgeon to perform morphological assessment and communicate with the patient and colleagues. Furthermore, the models also guided the choice and placement of pedicle screws. Moreover, the models were used to aid in virtual surgery and guide the actual surgical procedure. The mean ± SD postoperative scoliosis Cobb angle was 42° ± 32°, and no serious complications such as spinal cord or major vascular injury occurred. The use of computer-designed polystyrene models could provide more accurate morphometric information and facilitate surgical correction of complex severe spinal deformity. PMID:20213294

Development of a model with which to predict the life expectancy of patients with spinal epidural metastasis.

PubMed

Bartels, Ronald H M A; Feuth, Ton; van der Maazen, Richard; Verbeek, André L M; Kappelle, Arnoud C; André Grotenhuis, J; Leer, Jan Willem

2007-11-01

The surgical treatment of spinal epidural metastasis is evolving. To be a surgical candidate, a patient should have a life expectancy of at least 3 months. Estimation of survival by experienced specialists has proven to be unreliable. The Cox proportional hazards model was used to make a prediction model. To validate the model, Efron optimism correction by bootstrapping was performed. Retrospective data of patients treated for a spinal metastasis were used. Possible predictive factors were defined based on clinical experience and the literature. Statistical methods and clinical knowledge were also used to reveal an optimal set of predictors of survival. Data from patients treated at the Department of Radiation Oncology for spinal metastasis between 1998 and 2005 were evaluated. The case notes of 219 patients form the base of this study. In the final model, only 5 variables were required to predict the survival of a patient with spinal metastasis: sex, location of the primary lesion, intentional curative treatment of the primary tumor, cervical location of the spinal metastasis, and Karnofsky performance score. Examples with different predictors are given. The R(2) (N) index of Nagelkerke was 0.36 (95% confidence interval [95% CI], 0.28-0.48) and the c-index 0.72 (95% CI, 0.68-0.77). A reliable and simple model with which to predict the survival of a patient with spinal epidural metastasis is presented. Without the need for extensive investigations, survival can be predicted and only 5 easily obtainable parameters are required.

Influence of Spinal Manipulative Therapy Force Magnitude and Application Site on Spinal Tissue Loading: A Biomechanical Robotic Serial Dissection Study in Porcine Motion Segments.

PubMed

Funabashi, Martha; Nougarou, François; Descarreaux, Martin; Prasad, Narasimha; Kawchuk, Greg

In order to define the relation between spinal manipulative therapy (SMT) input parameters and the distribution of load within spinal tissues, the aim of this study was to determine the influence of force magnitude and application site when SMT is applied to cadaveric spines. In 10 porcine cadavers, a servo-controlled linear actuator motor provided a standardized SMT simulation using 3 different force magnitudes (100N, 300N, and 500N) to 2 different cutaneous locations: L3/L4 facet joint (FJ), and L4 transverse processes (TVP). Vertebral kinematics were tracked optically using indwelling bone pins, the motion segment removed and mounted in a parallel robot equipped with a 6-axis load cell. The kinematics of each SMT application were replicated robotically. Serial dissection of spinal structures was conducted to quantify loading characteristics of discrete spinal tissues. Forces experienced by the L3/L4 segment and spinal structures during SMT replication were recorded and analyzed. Spinal manipulative therapy force magnitude and application site parameters influenced spinal tissues loading. A significant main effect (P < .05) of force magnitude was observed on the loads experienced by the intact specimen and supra- and interspinous ligaments. The main effect of application site was also significant (P < .05), influencing the loading of the intact specimen and facet joints, capsules, and ligamentum flavum (P < .05). Spinal manipulative therapy input parameters of force magnitude and application site significantly influence the distribution of forces within spinal tissues. By controlling these SMT parameters, clinical outcomes may potentially be manipulated. Copyright © 2017. Published by Elsevier Inc.

Rapid activity-dependent modulation of the intrinsic excitability through up-regulation of KCNQ/Kv7 channel function in neonatal spinal motoneurons.

PubMed

Lombardo, Joseph; Sun, Jianli; Harrington, Melissa A

2018-01-01

Activity-dependent changes in the properties of the motor system underlie the necessary adjustments in its responsiveness on the basis of the environmental and developmental demands of the organism. Although plastic changes in the properties of the spinal cord have historically been neglected because of the archaic belief that the spinal cord is constituted by a hardwired network that simply relays information to muscles, plenty of evidence has been accumulated showing that synapses impinging on spinal motoneurons undergo short- and long-term plasticity. In the brain, brief changes in the activity level of the network have been shown to be paralleled by changes in the intrinsic excitability of the neurons and are suggested to either reinforce or stabilize the changes at the synaptic level. However, rapid activity-dependent changes in the intrinsic properties of spinal motoneurons have never been reported. In this study, we show that in neonatal mice the intrinsic excitability of spinal motoneurons is depressed after relatively brief but sustained changes in the spinal cord network activity. Using electrophysiological techniques together with specific pharmacological blockers of KCNQ/Kv7 channels, we demonstrate their involvement in the reduction of the intrinsic excitability of spinal motoneurons. This action results from an increased M-current, the product of the activation of KCNQ/Kv7 channels, which leads to a hyperpolarization of the resting membrane potential and a decrease in the input resistance of spinal motoneurons. Computer simulations showed that specific up-regulations in KCNQ/Kv7 channels functions lead to a modulation of the intrinsic excitability of spinal motoneurons as observed experimentally. These results indicate that KCNQ/Kv7 channels play a fundamental role in the activity-dependent modulation of the excitability of spinal motoneurons.

Learning from the spinal cord: How the study of spinal cord plasticity informs our view of learning

PubMed Central

Grau, James W.

2013-01-01

The paper reviews research examining whether and how training can induce a lasting change in spinal cord function. A framework for the study of learning, and some essential issues in experimental design, are discussed. A core element involves delayed assessment under common conditions. Research has shown that brain systems can induce a lasting (memory-like) alteration in spinal function. Neurons within the lower (lumbosacral) spinal cord can also adapt when isolated from the brain by means of a thoracic transection. Using traditional learning paradigms, evidence suggests that spinal neurons support habituation and sensitization as well as Pavlovian and instrumental conditioning. At a neurobiological level, spinal systems support phenomena (e.g., long-term potentiation), and involve mechanisms (e.g., NMDA mediated plasticity, protein synthesis) implicated in brain-dependent learning and memory. Spinal learning also induces modulatory effects that alter the capacity for learning. Uncontrollable/unpredictable stimulation disables the capacity for instrumental learning and this effect has been linked to the cytokine tumor necrosis factor (TNF). Predictable/controllable stimulation enables learning and counters the adverse effects of uncontrollable simulation through a process that depends upon brain-derived neurotrophic factor (BDNF). Finally, uncontrollable, but not controllable, nociceptive stimulation impairs recovery after a contusion injury. A process-oriented approach (neurofunctionalism) is outlined that encourages a broader view of learning phenomena. PMID:23973905

Development of an integrated CAD-FEA system for patient-specific design of spinal cages.

PubMed

Zhang, Mingzheng; Pu, Fang; Xu, Liqiang; Zhang, Linlin; Liang, Hang; Li, Deyu; Wang, Yu; Fan, Yubo

2017-03-01

Spinal cages are used to create a suitable mechanical environment for interbody fusion in cases of degenerative spinal instability. Due to individual variations in bone structures and pathological conditions, patient-specific cages can provide optimal biomechanical conditions for fusion, strengthening patient recovery. Finite element analysis (FEA) is a valuable tool in the biomechanical evaluation of patient-specific cage designs, but the time- and labor-intensive process of modeling limits its clinical application. In an effort to facilitate the design and analysis of patient-specific spinal cages, an integrated CAD-FEA system (CASCaDeS, comprehensive analytical spinal cage design system) was developed. This system produces a biomechanical-based patient-specific design of spinal cages and is capable of rapid implementation of finite element modeling. By comparison with commercial software, this system was validated and proven to be both accurate and efficient. CASCaDeS can be used to design patient-specific cages with a superior biomechanical performance to commercial spinal cages.

Naturally Occurring Disk Herniation in Dogs: An Opportunity for Pre-Clinical Spinal Cord Injury Research

PubMed Central

Levine, Gwendolyn J.; Porter, Brian F.; Topp, Kimberly; Noble-Haeusslein, Linda J.

2011-01-01

Abstract Traumatic spinal cord injuries represent a significant source of morbidity in humans. Despite decades of research using experimental models of spinal cord injury to identify candidate therapeutics, there has been only limited progress toward translating beneficial findings to human spinal cord injury. Thoracolumbar intervertebral disk herniation is a naturally occurring disease that affects dogs and results in compressive/contusive spinal cord injury. Here we discuss aspects of this disease that are analogous to human spinal cord injury, including injury mechanisms, pathology, and metrics for determining outcomes. We address both the strengths and weaknesses of conducting pre-clinical research in these dogs, and include a review of studies that have utilized these animals to assess efficacy of candidate therapeutics. Finally, we consider a two-species approach to pre-clinical data acquisition, beginning with a reproducible model of spinal cord injury in the rodent as a tool for discovery with validation in pet dogs with intervertebral disk herniation. PMID:21438715

The effects of model composition design choices on high-fidelity simulations of motoneuron recruitment and firing behaviors

NASA Astrophysics Data System (ADS)

Allen, John M.; Elbasiouny, Sherif M.

2018-06-01

Objective. Computational models often require tradeoffs, such as balancing detail with efficiency; yet optimal balance should incorporate sound design features that do not bias the results of the specific scientific question under investigation. The present study examines how model design choices impact simulation results. Approach. We developed a rigorously-validated high-fidelity computational model of the spinal motoneuron pool to study three long-standing model design practices which have yet to be examined for their impact on motoneuron recruitment, firing rate, and force simulations. The practices examined were the use of: (1) generic cell models to simulate different motoneuron types, (2) discrete property ranges for different motoneuron types, and (3) biological homogeneity of cell properties within motoneuron types. Main results. Our results show that each of these practices accentuates conditions of motoneuron recruitment based on the size principle, and minimizes conditions of mixed and reversed recruitment orders, which have been observed in animal and human recordings. Specifically, strict motoneuron orderly size recruitment occurs, but in a compressed range, after which mixed and reverse motoneuron recruitment occurs due to the overlap in electrical properties of different motoneuron types. Additionally, these practices underestimate the motoneuron firing rates and force data simulated by existing models. Significance. Our results indicate that current modeling practices increase conditions of motoneuron recruitment based on the size principle, and decrease conditions of mixed and reversed recruitment order, which, in turn, impacts the predictions made by existing models on motoneuron recruitment, firing rate, and force. Additionally, mixed and reverse motoneuron recruitment generated higher muscle force than orderly size motoneuron recruitment in these simulations and represents one potential scheme to increase muscle efficiency. The examined model design practices, as well as the present results, are applicable to neuronal modeling throughout the nervous system.

The effects of model composition design choices on high-fidelity simulations of motoneuron recruitment and firing behaviors.

PubMed

Allen, John M; Elbasiouny, Sherif M

2018-06-01

Computational models often require tradeoffs, such as balancing detail with efficiency; yet optimal balance should incorporate sound design features that do not bias the results of the specific scientific question under investigation. The present study examines how model design choices impact simulation results. We developed a rigorously-validated high-fidelity computational model of the spinal motoneuron pool to study three long-standing model design practices which have yet to be examined for their impact on motoneuron recruitment, firing rate, and force simulations. The practices examined were the use of: (1) generic cell models to simulate different motoneuron types, (2) discrete property ranges for different motoneuron types, and (3) biological homogeneity of cell properties within motoneuron types. Our results show that each of these practices accentuates conditions of motoneuron recruitment based on the size principle, and minimizes conditions of mixed and reversed recruitment orders, which have been observed in animal and human recordings. Specifically, strict motoneuron orderly size recruitment occurs, but in a compressed range, after which mixed and reverse motoneuron recruitment occurs due to the overlap in electrical properties of different motoneuron types. Additionally, these practices underestimate the motoneuron firing rates and force data simulated by existing models. Our results indicate that current modeling practices increase conditions of motoneuron recruitment based on the size principle, and decrease conditions of mixed and reversed recruitment order, which, in turn, impacts the predictions made by existing models on motoneuron recruitment, firing rate, and force. Additionally, mixed and reverse motoneuron recruitment generated higher muscle force than orderly size motoneuron recruitment in these simulations and represents one potential scheme to increase muscle efficiency. The examined model design practices, as well as the present results, are applicable to neuronal modeling throughout the nervous system.

Applying a Web and Simulation-Based System for Adaptive Competence Assessment of Spinal Anaesthesia

NASA Astrophysics Data System (ADS)

Hockemeyer, Cord; Nussbaumer, Alexander; Lövquist, Erik; Aboulafia, Annette; Breen, Dorothy; Shorten, George; Albert, Dietrich

The authors present an approach for implementing a system for the assessment of medical competences using a haptic simulation device. Based on Competence based Knowledge Space Theory (CbKST), information on the learners’ competences is gathered from different sources (test questions, data from the simulator, and supervising experts’ assessments).

Pharmacokinetics of amikacin in serum and in tissue contiguous with pressure sores in humans with spinal cord injury.

PubMed Central

Segal, J L; Brunnemann, S R; Eltorai, I M

1990-01-01

Pressure sores are a common occurrence in immobilized patients. They increase morbidity and mortality and impede rehabilitation. Antibiotics are routinely used to assist in effecting a cure when infection is present. Nevertheless, for patients with spinal cord injuries (SCI), strategies for effective therapy with antibiotics based on measurement of concentrations in tissue and pharmacokinetic behavior in extravascular spaces do not exist. By analyzing the concentration-time profile and protein binding of amikacin in the interstitial fluid (IF) in contact with pressure sores, we found that the disposition of amikacin in the tissue contiguous with pressure sores appears to be governed by simultaneous first-order and capacity-limited pharmacokinetic behavior. Amikacin disposition in IF proceeded without a simple relationship to amikacin concentrations in serum, and the time course in IF was not accurately simulated by linear models of amikacin pharmacokinetic behavior. Total amikacin clearance estimated from a pharmacokinetic model using simultaneous first-order and nonlinear intercompartmental transfer of amikacin was not significantly different from clearance calculated by us in a prior study of amikacin pharmacokinetic behavior in patients with SCI. In patients with SCI, optimal use of amikacin in the treatment of infected pressure sores is contingent upon accurate characterization of the pharmacokinetic behavior of this aminoglycoside in serum and in the IF in contact with these lesions. Only methods which quantitate amikacin concentration and protein binding in IF and incorporate a model that can simultaneously simulate nonlinear and linear disposition processes should be relied upon to influence therapeutic decision making. PMID:2386372

Forecasting Financial Resources for Future Traumatic Spinal Cord Injury Care Using Simulation Modeling.

PubMed

Ahn, Henry; Lewis, Rachel; Santos, Argelio; Cheng, Christiana L; Noonan, Vanessa K; Dvorak, Marcel F; Singh, Anoushka; Linassi, A Gary; Christie, Sean; Goytan, Michael; Atkins, Derek

2017-10-15

Survivors of traumatic spinal cord injury (tSCI) have intense healthcare needs during acute and rehabilitation care and often through the rest of life. To prepare for a growing and aging population, simulation modeling was used to forecast the change in healthcare financial resources and long-term patient outcomes between 2012 and 2032. The model was developed with data from acute and rehabilitation care facilities across Canada participating in the Access to Care and Timing project. Future population and tSCI incidence for 2012 and 2032 were predicted with data from Statistics Canada and the Canadian Institute for Health Information. The projected tSCI incidence for 2012 was validated with actual data from the Rick Hansen SCI Registry of the participating facilities. Using a medium growth scenario, in 2032, the projected median age of persons with tSCI is 57 and persons 61 and older will account for 46% of injuries. Admissions to acute and rehabilitation facilities in 2032 were projected to increase by 31% and 25%, respectively. Because of the demographic shift to an older population, an increase in total population life expectancy with tSCI of 13% was observed despite a 22% increase in total life years lost to tSCI between 2012 and 2032. Care cost increased 54%, and rest of life cost increased 37% in 2032, translating to an additional CAD $16.4 million. With the demographics and management of tSCI changing with an aging population, accurate projections for the increased demand on resources will be critical for decision makers when planning the delivery of healthcare after tSCI.

Development of a Personalized Model for Pressure Ulcer Prevention Acutely Following Spinal Cord Injury: Biomarkers of Muscle Composition and Resilience

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-1-0618 TITLE: Development of a Personalized Model for Pressure Ulcer Prevention Acutely Following Spinal Cord Injury...Model for Pressure Ulcer Prevention Acutely Following Spinal Cord Injury: Biomarkers of Muscle Composition and Resilience 5a. CONTRACT NUMBER...military and veterans. All persons with SCI are at increased risk of pressure ulcer development which remains one of the most significant secondary

Modeling and Identification of a Realistic Spiking Neural Network and Musculoskeletal Model of the Human Arm, and an Application to the Stretch Reflex.

PubMed

Sreenivasa, Manish; Ayusawa, Ko; Nakamura, Yoshihiko

2016-05-01

This study develops a multi-level neuromuscular model consisting of topological pools of spiking motor, sensory and interneurons controlling a bi-muscular model of the human arm. The spiking output of motor neuron pools were used to drive muscle actions and skeletal movement via neuromuscular junctions. Feedback information from muscle spindles were relayed via monosynaptic excitatory and disynaptic inhibitory connections, to simulate spinal afferent pathways. Subject-specific model parameters were identified from human experiments by using inverse dynamics computations and optimization methods. The identified neuromuscular model was used to simulate the biceps stretch reflex and the results were compared to an independent dataset. The proposed model was able to track the recorded data and produce dynamically consistent neural spiking patterns, muscle forces and movement kinematics under varying conditions of external forces and co-contraction levels. This additional layer of detail in neuromuscular models has important relevance to the research communities of rehabilitation and clinical movement analysis by providing a mathematical approach to studying neuromuscular pathology.

Modeling the neuroanatomic propagation of ALS in the spinal cord

NASA Astrophysics Data System (ADS)

Drawert, Brian; Thakore, Nimish; Mitchell, Brian; Pioro, Erik; Ravits, John; Petzold, Linda R.

2017-07-01

Recent hypotheses of amyotrophic lateral sclerosis (ALS) progression have posited a point-source origin of motor neuron death with neuroanatomic propagation either contiguously to adjacent regions, or along networks via axonal and synaptic connections. Although the molecular mechanisms of propagation are unknown, one leading hypothesis is a "prion-like" spread of misfolded and aggregated proteins, including SOD1 and TDP-43. We have developed a mathematical model representing cellular and molecular spread of ALS in the human spinal cord. Our model is based on the stochastic reaction-diffusion master equation approach using a tetrahedral discretized space to capture the complex geometry of the spinal cord. Domain dimension and shape was obtained by reconstructing human spinal cord from high-resolution magnetic resonance (MR) images and known gross and histological neuroanatomy. Our preliminary results qualitatively recapitulate the clinically observed pattern of spread of ALS thorough the spinal cord.

The radiation dosimetry of intrathecally administered radionuclides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stabin, M.G.; Evans, J.F.

The radiation dose to the spine, spinal cord, marrow, and other organs of the body from intrathecal administration of several radiopharmaceuticals was studied. Anatomic models were developed for the spine, spinal cerebrospinal fluid (CSF), spinal cord, spinal skeleton, cranial skeleton, and cranial CSF. A kinetic model for the transport of CSF was used to determine residence times in the CSF; material leaving the CSF was thereafter assumed to enter the bloodstream and follow the kinetics of the radiopharmaceutical as if intravenously administered. The radiation transport codes MCNP and ALGAMP were used to model the electron and photon transport and energymore » deposition. The dosimetry of Tc-99m DTPA and HSA, In-111 DTPA, I-131 HSA, and Yb-169 DTPA was studied. Radiation dose profiles for the spinal cord and marrow in the spine were developed and average doses to all other organs were estimated, including dose distributions within the bone and marrow.« less

Effect of Lumbar Lordosis on the Adjacent Segment in Transforaminal Lumbar Interbody Fusion: A Finite Element Analysis.

PubMed

Zhao, Xin; Du, Lin; Xie, Youzhuan; Zhao, Jie

2018-06-01

We used a finite element (FE) analysis to investigate the biomechanical changes caused by transforaminal lumbar interbody fusion (TLIF) at the L4-L5 level by lumbar lordosis (LL) degree. A lumbar FE model (L1-S5) was constructed based on computed tomography scans of a 30-year-old healthy male volunteer (pelvic incidence,= 50°; LL, 52°). We investigated the influence of LL on the biomechanical behavior of the lumbar spine after TLIF in L4-L5 fusion models with 57°, 52°, 47°, and 40° LL. The LL was defined as the angle between the superior end plate of L1 and the superior end plate of S1. A 150-N vertical axial preload was imposed on the superior surface of L3. A 10-N/m moment was simultaneously applied on the L3 superior surface along the radial direction to simulate the 4 basic physiologic motions of flexion, extension, lateral bending, and torsion in the numeric simulations. The range of motion (ROM) and intradiscal pressure (IDP) of L3-L4 were evaluated and compared in the simulated cases. In all motion patterns, the ROM and IDP were both increased after TLIF. In addition, the decrease in lordosis generally increased the ROM and IDP in all motion patterns. This FE analysis indicated that decreased spinal lordosis may evoke overstress of the adjacent segment and increase the risk of the pathologic development of adjacent segment degeneration; thus, adjacent segment degeneration should be considered when planning a spinal fusion procedure. Copyright © 2018. Published by Elsevier Inc.

Restrained Differential Growth: The Initiating Event of Adolescent Idiopathic Scoliosis?

PubMed

Crijns, Tom Joris; Stadhouder, Agnita; Smit, Theodoor Henri

2017-06-15

An experimental model study and a short review of literature. The purpose of this study was to explore a new hypothesis suggesting that the curvatures seen in adolescent idiopathic scoliosis (AIS) originate from restrained differential growth between the vertebral column and the surrounding musculo-ligamentary structures. Despite decades of research, there is no generally accepted theory on the physical origin of the severe spinal deformations seen in AIS. The prevailing theories tend to focus on left-right asymmetry, rotational instability, or the sagittal spinal profile in idiopathic scoliosis. We test our hypothesis with a physical model of the spine that simulates growth, counteracted by ligaments and muscles, modeled by tethers and springs. Growth of the spine is further restrained by an anterior band representing the thorax, the linea alba, and abdominal musculature. We also explore literature in search of molecular mechanisms that may induce differential growth. Differential growth in the restrained spine model first induces hypokyphosis and mild lateral bending of the thoracic spine, but then suddenly escalates into a scoliotic deformity, consistent with clinical observations of AIS. The band simulating the ventral structures of the body had a pivotal effect on sagittal curvature and the initiation of lateral bending and rotation. In literature, several molecular mechanisms were found that may explain the occurrence of differential growth between the spine and the musculo-ligamentary structures. While AIS is a three-dimensional deformation of the spine, it appears that restrained differential growth in the sagittal plane can result in lateral bending and rotation without a pre-existing left-right asymmetry. This supports the concept that AIS may result from a growth imbalance rather than a local anatomical defect. N/A.

Hybrid Rigid-Deformable Model for Prediction of Neighboring Intervertebral Disk Loads During Flexion Movement After Lumbar Interbody Fusion at L3-4 Level.

PubMed

Tuan Dao, Tien

2017-03-01

Knowledge of spinal loads in neighboring disks after interbody fusion plays an important role in the clinical decision of this treatment as well as in the elucidation of its effect. However, controversial findings are still noted in the literature. Moreover, there are no existing models for efficient prediction of intervertebral disk stresses within annulus fibrosus (AF) and nucleus pulposus (NP) regions. In this present study, a new hybrid rigid-deformable modeling workflow was established to quantify the mechanical stress behaviors within AF and NP regions of the L1-2, L2-3, and L4-5 disks after interbody fusion at L3-4 level. The changes in spinal loads were compared with results of the intact model without interbody fusion. The fusion outcomes revealed maximal stress changes (10%) in AF region of L1-2 disk and in NP region of L2-3 disk. The minimal stress change (1%) is noted at the NP region of the L1-2 disk. The validation of simulation outcomes of fused and intact lumbar spine models against those of other computational models and in vivo measurements showed good agreements. Thus, this present study may be used as a novel design guideline for a specific implant and surgical scenario of the lumbar spine disorders.

Neuroprotective effect of curcumin on spinal cord in rabbit model with ischemia/reperfusion.

PubMed

Liu, Zhi-Qiang; Xing, Shan-Shan; Zhang, Wei

2013-03-01

Ischemic/reperfusion (I/R) injury of the spinal cord is a serious complication that can result from thoracoabdominal aortic surgery. To investigate the neuroprotective effect of curcumin against I/R injury in a rabbit model. A total of 36 rabbits were randomly divided into three groups: sham, I/R, and curcumin-treated group. Rabbits were subject to 30-min aortic occlusion to induce transient spinal cord ischemia. Neurological function was observed after reperfusion and spinal cord segment (L3-L5) was collected for histopathological evaluation. Malondialdehyde (MDA) and total superoxide dismutase (SOD) activity were also assayed. Rabbits in I/R group were induced to paraplegia. While after 48-hour treatment, compared with I/R group, curcumin significantly improved neurological function, reduced cell apoptosis and MDA levels as well as increased SOD activity (P < 0.05). The results suggest that curcumin, at least in an animal model, can attenuate transient spinal cord ischemic injury potentially via reducing oxidative damage, which may provide a novel approach in the treatment of spinal cord ischemic injury.

Biomechanical implications of lumbar spinal ligament transection.

PubMed

Von Forell, Gregory A; Bowden, Anton E

2014-11-01

Many lumbar spine surgeries either intentionally or inadvertently damage or transect spinal ligaments. The purpose of this work was to quantify the previously unknown biomechanical consequences of isolated spinal ligament transection on the remaining spinal ligaments (stress transfer), vertebrae (bone remodelling stimulus) and intervertebral discs (disc pressure) of the lumbar spine. A finite element model of the full lumbar spine was developed and validated against experimental data and tested in the primary modes of spinal motion in the intact condition. Once a ligament was removed, stress increased in the remaining spinal ligaments and changes occurred in vertebral strain energy, but disc pressure remained similar. All major biomechanical changes occurred at the same spinal level as the transected ligament, with minor changes at adjacent levels. This work demonstrates that iatrogenic damage to spinal ligaments disturbs the load sharing within the spinal ligament network and may induce significant clinically relevant changes in the spinal motion segment.

Simulation Learning: PC-Screen Based (PCSB) versus High Fidelity Simulation (HFS)

DTIC Science & Technology

2012-08-01

methods for the use of simulation for teaching clinical skills to military and civilian clinicians . High fidelity simulation is an expensive method of...without the knowledge and approval of the IRB. Changes include, but not limited to, modifications in study design, recruitment process and number of...Person C-Collar simulation algorithm Pathway A Scenario A - Spinal stabilization: Sub processes Legend: Pathway Points Complex task to be performed by

Spinal cord injury: overview of experimental approaches used to restore locomotor activity.

PubMed

Fakhoury, Marc

2015-01-01

Spinal cord injury affects more than 2.5 million people worldwide and can lead to paraplegia and quadriplegia. Anatomical discontinuity in the spinal cord results in disruption of the impulse conduction that causes temporary or permanent changes in the cord's normal functions. Although axonal regeneration is limited, damage to the spinal cord is often accompanied by spontaneous plasticity and axon regeneration that help improve sensory and motor skills. The recovery process depends mainly on synaptic plasticity in the preexisting circuits and on the formation of new pathways through collateral sprouting into neighboring denervated territories. However, spontaneous recovery after spinal cord injury can go on for several years, and the degree of recovery is very limited. Therefore, the development of new approaches that could accelerate the gain of motor function is of high priority to patients with damaged spinal cord. Although there are no fully restorative treatments for spinal injury, various rehabilitative approaches have been tested in animal models and have reached clinical trials. In this paper, a closer look will be given at the potential therapies that could facilitate axonal regeneration and improve locomotor recovery after injury to the spinal cord. This article highlights the application of several interventions including locomotor training, molecular and cellular treatments, and spinal cord stimulation in the field of rehabilitation research. Studies investigating therapeutic approaches in both animal models and individuals with injured spinal cords will be presented.

Optical monitoring of spinal cord hemodynamics, a feasibility study

NASA Astrophysics Data System (ADS)

Shadgan, Babak; Kwon, Brian K.; Streijger, Femke; Manouchehri, Neda; So, Kitty; Shortt, Katelyn; Cripton, Peter A.; Macnab, Andrew

2017-02-01

Background: After an acute traumatic spinal cord injury (SCI), the spinal cord is subjected to ischemia, hypoxia, and increased hydrostatic pressure which exacerbate further secondary damage and neuronal deficit. The purpose of this pilot study was to explore the use of near infrared spectroscopy (NIRS) for non-invasive and real-time monitoring of these changes within the injured spinal cord in an animal model. NIRS is a non-invasive optical technique that utilizes light in the near infrared spectrum to monitor changes in the concentration of tissue chromophores from which alterations in tissues oxygenation and perfusion can be inferred in real time. Methods: A custom-made miniaturized NIRS sensor was developed to monitor spinal cord hemodynamics and oxygenation noninvasively and in real time simultaneously with invasive, intraparenchymal monitoring in a pig model of SCI. The spinal cord around the T10 injury site was instrumented with intraparenchymal probes inserted directly into the spinal cord to measure oxygen pressure, blood flow, and hydrostatic pressure, and the same region of the spinal cord was monitored with the custom-designed extradural NIRS probe. We investigated how well the extradural NIRS probe detected intraparenchymal changes adjacent to the injury site after alterations in systemic blood pressure, global hypoxia, and traumatic injury generated by a weight-drop contusion. Results: The NIRS sensor successfully identified periods of systemic hypoxia, re-ventilation and changes in spinal cord perfusion and oxygenation during alterations of mean arterial pressure and following spinal cord injury. Conclusion: This pilot study indicates that extradural NIRS monitoring of the spinal cord is feasible as a non-invasive optical method to identify changes in spinal cord hemodynamics and oxygenation in real time. Further development of this technique would allow clinicians to monitor real-time physiologic changes within the injured spinal cord during the acute post-injury period.

An ex vivo laser-induced spinal cord injury model to assess mechanisms of axonal degeneration in real-time.

PubMed

Okada, Starlyn L M; Stivers, Nicole S; Stys, Peter K; Stirling, David P

2014-11-25

Injured CNS axons fail to regenerate and often retract away from the injury site. Axons spared from the initial injury may later undergo secondary axonal degeneration. Lack of growth cone formation, regeneration, and loss of additional myelinated axonal projections within the spinal cord greatly limits neurological recovery following injury. To assess how central myelinated axons of the spinal cord respond to injury, we developed an ex vivo living spinal cord model utilizing transgenic mice that express yellow fluorescent protein in axons and a focal and highly reproducible laser-induced spinal cord injury to document the fate of axons and myelin (lipophilic fluorescent dye Nile Red) over time using two-photon excitation time-lapse microscopy. Dynamic processes such as acute axonal injury, axonal retraction, and myelin degeneration are best studied in real-time. However, the non-focal nature of contusion-based injuries and movement artifacts encountered during in vivo spinal cord imaging make differentiating primary and secondary axonal injury responses using high resolution microscopy challenging. The ex vivo spinal cord model described here mimics several aspects of clinically relevant contusion/compression-induced axonal pathologies including axonal swelling, spheroid formation, axonal transection, and peri-axonal swelling providing a useful model to study these dynamic processes in real-time. Major advantages of this model are excellent spatiotemporal resolution that allows differentiation between the primary insult that directly injures axons and secondary injury mechanisms; controlled infusion of reagents directly to the perfusate bathing the cord; precise alterations of the environmental milieu (e.g., calcium, sodium ions, known contributors to axonal injury, but near impossible to manipulate in vivo); and murine models also offer an advantage as they provide an opportunity to visualize and manipulate genetically identified cell populations and subcellular structures. Here, we describe how to isolate and image the living spinal cord from mice to capture dynamics of acute axonal injury.

Effect of spinal needle characteristics on measurement of spinal canal opening pressure.

PubMed

Bellamkonda, Venkatesh R; Wright, Thomas C; Lohse, Christine M; Keaveny, Virginia R; Funk, Eric C; Olson, Michael D; Laack, Torrey A

2017-05-01

A wide variety of spinal needles are used in clinical practice. Little is currently known regarding the impact of needle length, gauge, and tip type on the needle's ability to measure spinal canal opening pressure. This study aimed to investigate the relationship between these factors and the opening-pressure measurement or time to obtain an opening pressure. Thirteen distinct spinal needles, chosen to isolate the effects of length, gauge, and needle-point type, were prospectively tested on a lumbar puncture simulator. The key outcomes were the opening-pressure measurement and the time required to obtain that measure. Pressures were recorded at 10-s intervals until 3 consecutive, identical readings were observed. Time to measure opening pressure increased with increasing spinal needle length, increasing gauge, and the Quincke-type (cutting) point (P<0.001 for all). The time to measurement ranged from 30s to 530s, yet all needle types were able to obtain a consistent opening pressure measure. Although opening pressure estimates are unlikely to vary markedly by needle type, the time required to obtain the measurement increased with increasing needle length and gauge and with Quincke-type needles. Copyright © 2017 Elsevier Inc. All rights reserved.

Validation of the Cat as a Model for the Human Lumbar Spine During Simulated High-Velocity, Low-Amplitude Spinal Manipulation

PubMed Central

Pickar, Joel G.; Khalsa, Partap S.

2012-01-01

High-velocity, low-amplitude spinal manipulation (HVLA-SM) is an efficacious treatment for low back pain, although the physiological mechanisms underlying its effects remain elusive. The lumbar facet joint capsule (FJC) is innervated with mechanically sensitive neurons and it has been theorized that the neurophysiological benefits of HVLA-SM are partially induced by stimulation of FJC neurons. Biomechanical aspects of this theory have been investigated in humans while neurophysiological aspects have been investigated using cat models. The purpose of this study was to determine the relationship between human and cat lumbar spines during HVLA-SM. Cat lumbar spine specimens were mechanically tested, using a displacement-controlled apparatus, during simulated HVLA-SM applied at L5, L6, and L7 that produced preload forces of ~25% bodyweight for 0.5 s and peak forces that rose to 50–100% bodyweight within ~125 ms, similar to that delivered clinically. Joint kinematics and FJC strain were measured optically. Human FJC strain and kinematics data were taken from a prior study. Regression models were established for FJC strain magnitudes as functions of factors species, manipulation site, and interactions thereof. During simulated HVLA-SM, joint kinematics in cat spines were greater in magnitude compared with humans. Similar to human spines, site-specific HVLA-SM produced regional cat FJC strains at distant motion segments. Joint motions and FJC strain magnitudes for cat spines were larger than those for human spine specimens. Regression relationships demonstrated that species, HVLA-SM site, and interactions thereof were significantly and moderately well correlated for HVLA-SM that generated tensile strain in the FJC. The relationships established in the current study can be used in future neurophysiological studies conducted in cats to extrapolate how human FJC afferents might respond to HVLA-SM. The data from the current study warrant further investigation into the clinical relevance of site targeted HVLA-SM. PMID:20590286

How the science and engineering of spaceflight contribute to understanding the plasticity of spinal cord injury

NASA Technical Reports Server (NTRS)

Edgerton, V. R.; Roy, R. R.; Hodgson, J. A.; Day, M. K.; Weiss, J.; Harkema, S. J.; Dobkin, B.; Garfinkel, A.; Konigsberg, E.; Koslovskaya, I.

2000-01-01

Space programs support experimental investigations related to the unique environment of space and to the technological developments from many disciplines of both science and engineering that contribute to space studies. Furthermore, interactions between scientists, engineers and administrators, that are necessary for the success of any science mission in space, promote interdiscipline communication, understanding and interests which extend well beyond a specific mission. NASA-catalyzed collaborations have benefited the spinal cord rehabilitation program at UCLA in fundamental science and in the application of expertise and technologies originally developed for the space program. Examples of these benefits include: (1) better understanding of the role of load in maintaining healthy muscle and motor function, resulting in a spinal cord injury (SCI) rehabilitation program based on muscle/limb loading; (2) investigation of a potentially novel growth factor affected by spaceflight which may help regulate muscle mass; (3) development of implantable sensors, electronics and software to monitor and analyze long-term muscle activity in unrestrained subjects; (4) development of hardware to assist therapies applied to SCI patients; and (5) development of computer models to simulate stepping which will be used to investigate the effects of neurological deficits (muscle weakness or inappropriate activation) and to evaluate therapies to correct these deficiencies.

[HEART RHYTHM VARIABILITY ANALYSIS AND ASSESSMENT OF THE SPINAL PAIN SYNDROME DURING DRY IMMERSION].

PubMed

Sun, I; Voronkov, Yu I; Ardashev, V N; Glukhova, S I

2015-01-01

The spinal pain syndrome appears in cosmonauts on both short and long-duration missions. This untoward factor may affect body systems functioning and complicate the successful accomplishment of space mission. Purpose of the investigation was to examine the lumbar spine and to elucidate whether its condition relates to the spinal pain development and changes in heart rate variability (HRV) in the microgravity environment. The experiment was conducted in dry immersion as a method of microgravity effects simulation. It was shown that in dry immersion locomotion reproduces the patterns peculiar for significant gravitational unloading. Spinal pain intensity, angles and heights of the lumbar intervertebral discs and HRV were measured in 19 selected volunteers. During the experiment, all the volunteers developed pains in the back that abated gradually. Pain dependence on the height of intervertebral discs and cardiac regulatory mechanisms were investigated.

Regeneration of Xenopus laevis spinal cord requires Sox2/3 expressing cells

PubMed Central

Muñoz, Rosana; Edwards-Faret, Gabriela; Moreno, Mauricio; Zuñiga, Nikole; Cline, Hollis; Larraín, Juan

2016-01-01

Spinal cord regeneration is very inefficient in humans, causing paraplegia and quadriplegia. Studying model organisms that can regenerate the spinal cord in response to injury could be useful for understanding the cellular and molecular mechanisms that explain why this process fails in humans. Here, we use Xenopus laevis as a model organism to study spinal cord repair. Histological and functional analyses showed that larvae at pre-metamorphic stages restore anatomical continuity of the spinal cord and recover swimming after complete spinal cord transection. These regenerative capabilities decrease with onset of metamorphosis. The ability to study regenerative and non-regenerative stages in Xenopus laevis makes it a unique model system to study regeneration. We studied the response of Sox2/3 expressing cells to spinal cord injury and their function in the regenerative process. We found that cells expressing Sox2 and/or Sox3 are present in the ventricular zone of regenerative animals and decrease in non-regenerative froglets. Bromodeoxyuridine (BrdU) experiments and in vivo time-lapse imaging studies using green fluorescent protein (GFP) expression driven by the Sox3 promoter showed a rapid, transient and massive proliferation of Sox2/3+ cells in response to injury in the regenerative stages. The in vivo imaging also demonstrated that Sox2/3+ neural progenitor cells generate neurons in response to injury. In contrast, these cells showed a delayed and very limited response in non-regenerative froglets. Sox2 knockdown and overexpression of a dominant negative form of Sox2 disrupts locomotor and anatomical-histological recovery. We also found that neurogenesis markers increase in response to injury in regenerative but not in non-regenerative animals. We conclude that Sox2 is necessary for spinal cord regeneration and suggest a model whereby spinal cord injury activates proliferation of Sox2/3 expressing cells and their differentiation into neurons, a mechanism that is lost in non-regenerative froglets. PMID:25797152

Buckling and bone modeling as factors in the development of idiopathic scoliosis.

PubMed

Goto, Manabu; Kawakami, Noriaki; Azegami, Hideyuki; Matsuyama, Yukihiro; Takeuchi, Kenzen; Sasaoka, Ryu

2003-02-15

Computational analysis using the finite-element method was used to examine a possible etiology of idiopathic scoliosis. To compare changes in the coronal and the transverse planes of idiopathic thoracic scoliosis with changes produced in a finite-element buckling model, and to investigate the influence of bone modeling on the buckling spine. Although it is now widely accepted that growth is related strongly to the onset and progression of scoliosis, the pathomechanism or etiology of idiopathic scoliosis still is not clear. A previous study showed that a buckling phenomenon caused by anterior spinal overgrowth can produce scoliosis, and that the fourth buckling mode matched the clinical characteristics associated with the thoracic type of idiopathic scoliosis. The fourth buckling mode occurs when the first, second, and third buckling modes are prevented. The spinal finite-element model used in this study consisted of 68,582 elements and 84,603 nodes. The transverse changes seen in the computed tomography images of 41 patients with idiopathic thoracic scoliosis (apex, T8; average Cobb angle, 52.5 degrees) were compared with those produced in the fourth buckling mode. Bone modeling (bone formation and resorption) was simulated as heat deformation caused by changes in temperature. The bone formation and resorption were simulated, respectively, by positive and negative volume changes in proportion to the stress that occurred in the buckling spine. Computed tomography images of scoliosis show that as the scoliosis becomes more severe, the thoracic cage decreases on the convex side of the curve and increases on the concave side. The opposite thoracic cage deformation was obtained in the fourth buckling mode. In patients with scoliosis, the sternum essentially remains in its original position with respect to the vertebrae, but in the linear buckling model, it shifted in the direction of vertebral body rotation. In contrast to clinical data, the incremental deformation resulting from bone formation corrected the original curve, and the thoracic cage distorted. On the other hand, incremental deformation resulting from bone resorption worsened the original curve, and the thoracic cage distorted in a manner similar to that described by the clinical data. This computational investigation suggests that scoliotic changes in the spinal column triggered by the buckling phenomenon are counteracted by bone formation, but worsened by bone resorption. The authors hypothesized that scoliosis progressed with resorption of loaded bone. However, it is unclear whether this hypothesis applies to a living body in practice because of the effects from additional factors.

Toll-like receptor 4 contributes to chronic itch, alloknesis and spinal astrocyte activation in male mice

PubMed Central

Liu, Tong; Han, Qingjian; Chen, Gang; Huang, Ya; Zhao, Lin-Xia; Berta, Temugin; Gao, Yong-Jing; Ji, Ru-Rong

2016-01-01

Increasing evidence suggests that Toll-like receptor 4 (TLR4) contributes importantly to spinal cord glial activation and chronic pain sensitization; however, its unique role in acute and chronic itch is unclear. In this study, we investigated the involvement of TLR4 in acute and chronic itch models in male mice using both transgenic and pharmacological approaches. Tlr4−/− mice exhibited normal acute itch induced by compound 48/80 and chloroquine, but these mice showed substantial reductions in scratching in chronic itch models of dry skin, induced by acetone and diethyether followed by water (AEW), contact dermatitis, and allergic contact dermatitis on the neck. Intrathecal (spinal) inhibition of TLR4 with lipopolysaccharide Rhodobacter sphaeroides (LPS-RS) did not affect acute itch but suppressed AEW-induced chronic itch. Compound 48/80 and AEW also produced robust alloknesis, a touch-elicited itch in wild-type mice, which was suppressed by intrathecal LPS-RS and Tlr4−/− deletion. AEW induced persistent upregulation of Tlr4 mRNA and increased TLR4 expression in GFAP-expressing astrocytes in spinal cord dorsal horn. AEW also induced TLR4-dependent astrogliosis (GFAP upregulation) in spinal cord. Intrathecal injection of astroglial inhibitor L-α-aminoadipate reduced AEW-induced chronic itch and alloknesis without affecting acute itch. Spinal TLR4 was also necessary for AEW-induced chronic itch in the cheek model. Interestingly, scratching plays an essential role in spinal astrogliosis, since AEW-induced astrogliosis was abrogated by putting Elizabethan Collars on the neck to prevent scratching the itchy skin. Our findings suggest that spinal TLR4 signaling is important for spinal astrocyte activation and astrogliosis that may underlie alloknesis and chronic itch. PMID:26645545

Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization

PubMed Central

Corleto, Jose A.; Bravo-Hernández, Mariana; Kamizato, Kota; Kakinohana, Osamu; Santucci, Camila; Navarro, Michael R.; Platoshyn, Oleksandr; Cizkova, Dasa; Lukacova, Nadezda; Taylor, Julian; Marsala, Martin

2015-01-01

The development of spinal hyper-reflexia as part of the spasticity syndrome represents one of the major complications associated with chronic spinal traumatic injury (SCI). The primary mechanism leading to progressive appearance of muscle spasticity is multimodal and may include loss of descending inhibitory tone, alteration of segmental interneuron-mediated inhibition and/or increased reflex activity to sensory input. Here, we characterized a chronic thoracic (Th 9) complete transection model of muscle spasticity in Sprague-Dawley (SD) rats. Isoflurane-anesthetized rats received a Th9 laminectomy and the spinal cord was transected using a scalpel blade. After the transection the presence of muscle spasticity quantified as stretch and cutaneous hyper-reflexia was identified and quantified as time-dependent changes in: i) ankle-rotation-evoked peripheral muscle resistance (PMR) and corresponding electromyography (EMG) activity, ii) Hoffmann reflex, and iii) EMG responses in gastrocnemius muscle after paw tactile stimulation for up to 8 months after injury. To validate the clinical relevance of this model, the treatment potency after systemic treatment with the clinically established anti-spastic agents baclofen (GABAB receptor agonist), tizanidine (α2-adrenergic agonist) and NGX424 (AMPA receptor antagonist) was also tested. During the first 3 months post spinal transection, a progressive increase in ankle rotation-evoked muscle resistance, Hoffmann reflex amplitude and increased EMG responses to peripherally applied tactile stimuli were consistently measured. These changes, indicative of the spasticity syndrome, then remained relatively stable for up to 8 months post injury. Systemic treatment with baclofen, tizanidine and NGX424 led to a significant but transient suppression of spinal hyper-reflexia. These data demonstrate that a chronic Th9 spinal transection model in adult SD rat represents a reliable experimental platform to be used in studying the pathophysiology of chronic spinal injury-induced spasticity. In addition a consistent anti-spastic effect measured after treatment with clinically effective anti-spastic agents indicate that this model can effectively be used in screening new anti-spasticity compounds or procedures aimed at modulating chronic spinal trauma-associated muscle spasticity. PMID:26713446

Stem Cells in Spinal Fusion

PubMed Central

Haudenschild, Dominik R.; Wegner, Adam M.; Klineberg, Eric O.

2017-01-01

Study Design: Review of literature. Objectives: This review of literature investigates the application of mesenchymal stem cells (MSCs) in spinal fusion, highlights potential uses in the development of bone grafts, and discusses limitations based on both preclinical and clinical models. Methods: A review of literature was conducted looking at current studies using stem cells for augmentation of spinal fusion in both animal and human models. Results: Eleven preclinical studies were found that used various animal models. Average fusion rates across studies were 59.8% for autograft and 73.7% for stem cell–based grafts. Outcomes included manual palpation and stressing of the fusion, radiography, micro–computed tomography (μCT), and histological analysis. Fifteen clinical studies, 7 prospective and 8 retrospective, were found. Fusion rates ranged from 60% to 100%, averaging 87.1% in experimental groups and 87.2% in autograft control groups. Conclusions: It appears that there is minimal clinical difference between commercially available stem cells and bone marrow aspirates indicating that MSCs may be a good choice in a patient with poor marrow quality. Overcoming morbidity and limitations of autograft for spinal fusion, remains a significant problem for spinal surgeons and further studies are needed to determine the efficacy of stem cells in augmenting spinal fusion. PMID:29238646

End-task versus in-task feedback to increase procedural learning retention during spinal anaesthesia training of novices.

PubMed

Lean, Lyn Li; Hong, Ryan Yee Shiun; Ti, Lian Kah

2017-08-01

Communication of feedback during teaching of practical procedures is a fine balance of structure and timing. We investigate if continuous in-task (IT) or end-task feedback (ET) is more effective in teaching spinal anaesthesia to medical students. End-task feedback was hypothesized to improve both short-term and long-term procedural learning retention as experiential learning promotes active learning after encountering errors during practice. Upon exposure to a 5-min instructional video, students randomized to IT or ET feedbacks were trained using a spinal simulator mannequin. A blinded expert tested the students using a spinal anaesthesia checklist in the short term (immediate) and long-term (average 4 months). Sixty-five students completed the training and testing. There were no differences in demographics of age or gender within IT or ET distributions. Both short-term and long-term learning retention of spinal anaesthesia ET feedback proved to be better (P < 0.01) than IT feedback. The time taken for ET students was shorter at long-term testing. End-task feedback improves both short-term and long-term procedural learning retention.

[Effect of electroacupuncture on expression of ionotropic glutamate receptor subunits and their genes in lumbar segments of spinal cord in rats with neuropathic pain].

PubMed

Ma, Cheng; Yu, Li; Yan, Li-ping

2010-12-01

To observe the effect of electroacupuncture (EA) on the expression of ionotropic glutamate receptor (iGluR) subunits and their mRNAs in the lumbar segments of spinal cord in rats with neuropathic pain, so as to explore its underlying mechanism in relieving spinal hyperalgesia. Thirty SD rats were randomly divided into control, model, and EA groups, with 10 rats in each. The spared nerve injury (SNI) model was established by ligature of the sural nerve after cutting off the common peroneal nerve and anterior tibial nerve. EA (2 Hz, 1 mA) was applied to "Huantiao" (GB 30) and "Weizhong" (BL 40) for 30 min, once daily for 7 days. Mechanical pain threshold was detected before and after modeling and before and after EA treatment. The expression levels of N-methyl-d-aspartic acid (NMDA) receptor subunits NR1 and NR 2 B,and AMPA receptor subunit GluR 1 of iGluR and their genes were assayed by Western blot and reverse transcription polymerase chain reaction (RT-PCR) separately. In comparison with control group, the mechanical pain thresholds were decreased significantly on day 2, 7 and day 14 following modeling in the model group (P < 0.05, P < 0.01). While compared with the model group, the pain threshold was increased considerably on day 14 in the EA group (P < 0.01). Compared with the control group, the expression levels of lumbar spinal cord NR 2 B and NR 2 B mRNA in the model group were increased significantly (P < 0.05), and those of lumbar spinal cord NR 1 and NR 1 mRNA, GluR 1 and GluR 1 mRNA in the model group increased slightly (P > 0.05). In comparison with the model group, the expression levels of lumbar spinal cord NR 2 B and NR 2 B mRNA in the EA group were downregulated remarkably (P < 0.05), and those of lumbar spinal cord NR 1 and NR 1 mRNA, GluR 1 and GluR 1 mRNA in the EA group down-regulated slightly (P > 0.05). EA can significantly suppress pain reaction in rats with neuropathic pain probably through down-regulating the expression of lumbar spinal cord NR 2 B protein and NR 2 B mRNA.

Three-Dimensional Mechanical Model of the Human Spine and the Versatility of its Use

NASA Astrophysics Data System (ADS)

Sokol, Milan; Velísková, Petra; Rehák, Ľuboš; Žabka, Martin

2014-03-01

The aim of the work is oriented towards the simulation or modeling of the lumbar and thoracic human spine as a load-bearing 3D system in a computer program (ANSYS). The human spine model includes a determination of the geometry based on X-ray pictures of frontal and lateral projections. For this reason, another computer code, BMPCOORDINATES, was developed as an aid to obtain the most precise and realistic model of the spine. Various positions, deformations, scoliosis, rotation and torsion can be modelled. Once the geometry is done, external loading on different spinal segments is entered; consequently, the response could be analysed. This can contribute a lot to medical practice as a tool for diagnoses, and developing implants or other artificial instruments for fixing the spine.

Irreversible Electroporation (IRE) in the Epidural Space of the Porcine Spine: Effects on Adjacent Structures

PubMed Central

Tam, Alda L.; Figueira, Tomas A.; Gagea, Mihai; Ensor, Joe E.; Dixon, Katherine; McWatters, Amanda; Gupta, Sanjay; Fuentes, David T.

2018-01-01

Purpose To determine the effects of irreversible electroporation (IRE) on the neural tissues following ablation in the epidural space of the porcine spine. Material and Methods The institutional animal care and use committee approved this study. With the IRE electrode positioned in the right lateral recess of the spinal epidural space, twenty CT-guided IRE ablations were performed using different applied voltages in four terminal animals. Histopathology of the neural tissues was assessed and used to select a voltage for a survival study. Sixteen CT-guided IRE ablations in the epidural space were performed using 667 V in four animals that were survived for 7-days. Clinical observation, magnetic resonance imaging (MRI) findings (obtained 6-hours post-IRE and pre-euthanasia),, histopathology, and simulated electric field strengths were assessed. A one-way analysis of variance (ANOVA) was used to compare the simulated electric field strength to histological findings. Results The mean distance between the IRE electrode and the spinal cord or nerve root was 1.71 ± 0.90 mm and 8.47 + 3.44 mm, respectively. There was no clinical evidence of paraplegia after IRE ablation. MRI and histopathology showed no neural-tissue lesions within the spinal cord; however, 31.2% (5/16) of nerve roots demonstrated moderate Wallerian degeneration in the survival group. Severity of histopathological injury in the survival group was not significantly related to either the simulated electric field strength or the distance between the IRE electrode and neural structure, (p >.05). Conclusions While the spinal cord appears resistant to the toxic effects of IRE, injury to the nerve roots may be a limiting factor for the use of IRE ablation in the epidural space. PMID:27266723

A valuable animal model of spinal cord injury to study motor dysfunctions, comorbid conditions, and aging associated diseases.

PubMed

Rouleau, Pascal; Guertin, Pierre A

2013-01-01

Most animal models of contused, compressed or transected spinal cord injury (SCI) require a laminectomy to be performed. However, despite advantages and disadvantages associated with each of these models, the laminectomy itself is generally associated with significant problems including longer surgery and anaesthesia (related post-operative complications), neuropathic pain, spinal instabilities, deformities, lordosis, and biomechanical problems, etc. This review provides an overview of findings obtained mainly from our laboratory that are associated with the development and characterization of a novel murine model of spinal cord transection that does not require a laminectomy. A number of studies successfully conducted with this model provided strong evidence that it constitutes a simple, reliable and reproducible transection model of complete paraplegia which is particularly useful for studies on large cohorts of wild-type or mutant animals - e.g., drug screening studies in vivo or studies aimed at characterizing neuronal and non-neuronal adaptive changes post-trauma. It is highly suitable also for studies aimed at identifying and developing new pharmacological treatments against aging associated comorbid problems and specific SCI-related dysfunctions (e.g., stereotyped motor behaviours such as locomotion, sexual response, defecation and micturition) largely related with 'command centers' located in lumbosacral areas of the spinal cord.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Medin, Paul M., E-mail: Paul.medin@utsouthwestern.ed; Boike, Thomas P.

Clinical implementation of spinal radiosurgery has increased rapidly in recent years, but little is known regarding human spinal cord tolerance to single-fraction irradiation. In contrast, preclinical studies in single-fraction spinal cord tolerance have been ongoing since the 1970s. The influences of field length, dose rate, inhomogeneous dose distributions, and reirradiation have all been investigated. This review summarizes literature regarding single-fraction spinal cord tolerance in preclinical models with an emphasis on practical clinical significance. The outcomes of studies that incorporate uniform irradiation are surprisingly consistent among multiple small- and large-animal models. Extensive investigation of inhomogeneous dose distributions in the rat hasmore » demonstrated a significant dose-volume effect while preliminary results from one pig study are contradictory. Preclinical spinal cord dose-volume studies indicate that dose distribution is more critical than the volume irradiated suggesting that neither dose-volume histogram analysis nor absolute volume constraints are effective in predicting complications. Reirradiation data are sparse, but results from guinea pig, rat, and pig studies are consistent with the hypothesis that the spinal cord possesses a large capacity for repair. The mechanisms behind the phenomena observed in spinal cord studies are not readily explained and the ability of dose response models to predict outcomes is variable underscoring the need for further investigation. Animal studies provide insight into the phenomena and mechanisms of radiosensitivity but the true significance of animal studies can only be discovered through clinical trials.« less

Kinematic response of the spine during simulated aircraft ejections.

PubMed

Damon, Andrew M; Lessley, David J; Salzar, Robert S; Bass, Cameron R; Shen, Francis H; Paskoff, Glenn R; Shender, Barry S

2010-05-01

Military aviators are susceptible to spinal injuries during high-speed ejection scenarios. These injuries commonly arise as a result of strains induced by extreme flexion or compression of the spinal column. This study characterizes the vertebral motion of two postmortem human surrogates (PMHS) during a simulated catapult phase of ejection on a horizontal decelerator sled. During testing, the PMHS were restrained supinely to a mock ejection seat and subjected to a horizontal deceleration profile directed along the local z-axis. Two midsized males (175.3 cm, 77.1 kg; 185.4 cm, 72.6 kg) were tested. High-rate motion capture equipment was used to measure the three-dimensional displacement of the head, vertebrae, and pelvis during the ejection event. The two PMHS showed generally similar kinematic motion. Head injury criterion (HIC) results were well below injury threshold levels for both specimens. The specimens both showed compression of the spine, with a reduction in length of 23.9 mm and 45.7 mm. Post-test autopsies revealed fractures in the C5, T1, and L1 vertebrae. This paper provides an analysis of spinal motion during an aircraft ejection.The injuries observed in the test subjects were consistent with those seen in epidemiological studies. Future studies should examine the effects of gender, muscle tensing, out-of-position (of head from neutral position) occupants, and external forces (e.g., windblast) on spinal kinematics during aircraft ejection.

The dosimetric impact of implants on the spinal cord dose during stereotactic body radiotherapy.

PubMed

Yazici, Gozde; Sari, Sezin Yuce; Yedekci, Fazli Yagiz; Yucekul, Altug; Birgi, Sumerya Duru; Demirkiran, Gokhan; Gultekin, Melis; Hurmuz, Pervin; Yazici, Muharrem; Ozyigit, Gokhan; Cengiz, Mustafa

2016-05-25

The effects of spinal implants on dose distribution have been studied for conformal treatment plans. However, the dosimetric impact of spinal implants in stereotactic body radiotherapy (SBRT) treatments has not been studied in spatial orientation. In this study we evaluated the effect of spinal implants placed in sawbone vertebra models implanted as in vivo instrumentations. Four different spinal implant reconstruction techniques were performed using the standard sawbone lumbar vertebrae model; 1. L2-L4 posterior instrumentation without anterior column reconstruction (PI); 2. L2-L4 anterior instrumentation, L3 corpectomy, and anterior column reconstruction with a titanium cage (AIAC); 3. L2-L4 posterior instrumentation, L3 corpectomy, and anterior column reconstruction with a titanium cage (PIAC); 4. L2-L4 anterior instrumentation, L3 corpectomy, and anterior column reconstruction with chest tubes filled with bone cement (AIABc). The target was defined as the spinous process and lamina of the lumbar (L) 3 vertebra. A thermoluminescent dosimeter (TLD, LiF:Mg,Ti) was located on the measurement point anterior to the spinal cord. The prescription dose was 8 Gy and the treatment was administered in a single fraction using a CyberKnife® (Accuray Inc., Sunnyvale, CA, USA). We performed two different treatment plans. In Plan A beam interaction with the rod was not limited. In plan B the rod was considered a structure of avoidance, and interaction between the rod and beam was prevented. TLD measurements were compared with the point dose calculated by the treatment planning system (TPS). In plan A, the difference between TLD measurement and the dose calculated by the TPS was 1.7 %, 2.8 %, and 2.7 % for the sawbone with no implant, PI, and PIAC models, respectively. For the AIAC model the TLD dose was 13.8 % higher than the TPS dose; the difference was 18.6 % for the AIABc model. In plan B for the AIAC and AIABc models, TLD measurement was 2.5 % and 0.9 % higher than the dose calculated by the TPS, respectively. Spinal implants may be present in the treatment field in patients scheduled to undergo SBRT. For the types of implants studied herein anterior rod instrumentation resulted in an increase in the spinal cord dose, whereas use of a titanium cage had a minimal effect on dose distribution. While planning SBRT in patients with spinal reconstructions, avoidance of the rod and preventing interaction between the rod and beam might be the optimal solution for preventing unexpectedly high spinal cord doses.

Thoracolumbar spine model with articulated ribcage for the prediction of dynamic spinal loading.

PubMed

Ignasiak, Dominika; Dendorfer, Sebastian; Ferguson, Stephen J

2016-04-11

Musculoskeletal modeling offers an invaluable insight into the spine biomechanics. A better understanding of thoracic spine kinetics is essential for understanding disease processes and developing new prevention and treatment methods. Current models of the thoracic region are not designed for segmental load estimation, or do not include the complex construct of the ribcage, despite its potentially important role in load transmission. In this paper, we describe a numerical musculoskeletal model of the thoracolumbar spine with articulated ribcage, modeled as a system of individual vertebral segments, elastic elements and thoracic muscles, based on a previously established lumbar spine model and data from the literature. The inverse dynamics simulations of the model allow the prediction of spinal loading as well as costal joints kinetics and kinematics. The intradiscal pressure predicted by the model correlated well (R(2)=0.89) with reported intradiscal pressure measurements, providing a first validation of the model. The inclusion of the ribcage did not affect segmental force predictions when the thoracic spine did not perform motion. During thoracic motion tasks, the ribcage had an important influence on the predicted compressive forces and muscle activation patterns. The compressive forces were reduced by up to 32%, or distributed more evenly between thoracic vertebrae, when compared to the predictions of the model without ribcage, for mild thoracic flexion and hyperextension tasks, respectively. The presented musculoskeletal model provides a tool for investigating thoracic spine loading and load sharing between vertebral column and ribcage during dynamic activities. Further validation for specific applications is still necessary. Copyright © 2015 Elsevier Ltd. All rights reserved.

Forecasting Financial Resources for Future Traumatic Spinal Cord Injury Care Using Simulation Modeling

PubMed Central

Ahn, Henry; Lewis, Rachel; Santos, Argelio; Cheng, Christiana L.; Dvorak, Marcel F.; Singh, Anoushka; Linassi, A. Gary; Christie, Sean; Goytan, Michael; Atkins, Derek

2017-01-01

Abstract Survivors of traumatic spinal cord injury (tSCI) have intense healthcare needs during acute and rehabilitation care and often through the rest of life. To prepare for a growing and aging population, simulation modeling was used to forecast the change in healthcare financial resources and long-term patient outcomes between 2012 and 2032. The model was developed with data from acute and rehabilitation care facilities across Canada participating in the Access to Care and Timing project. Future population and tSCI incidence for 2012 and 2032 were predicted with data from Statistics Canada and the Canadian Institute for Health Information. The projected tSCI incidence for 2012 was validated with actual data from the Rick Hansen SCI Registry of the participating facilities. Using a medium growth scenario, in 2032, the projected median age of persons with tSCI is 57 and persons 61 and older will account for 46% of injuries. Admissions to acute and rehabilitation facilities in 2032 were projected to increase by 31% and 25%, respectively. Because of the demographic shift to an older population, an increase in total population life expectancy with tSCI of 13% was observed despite a 22% increase in total life years lost to tSCI between 2012 and 2032. Care cost increased 54%, and rest of life cost increased 37% in 2032, translating to an additional CAD $16.4 million. With the demographics and management of tSCI changing with an aging population, accurate projections for the increased demand on resources will be critical for decision makers when planning the delivery of healthcare after tSCI. PMID:28594315

Automatic 3D segmentation of spinal cord MRI using propagated deformable models

NASA Astrophysics Data System (ADS)

De Leener, B.; Cohen-Adad, J.; Kadoury, S.

2014-03-01

Spinal cord diseases or injuries can cause dysfunction of the sensory and locomotor systems. Segmentation of the spinal cord provides measures of atrophy and allows group analysis of multi-parametric MRI via inter-subject registration to a template. All these measures were shown to improve diagnostic and surgical intervention. We developed a framework to automatically segment the spinal cord on T2-weighted MR images, based on the propagation of a deformable model. The algorithm is divided into three parts: first, an initialization step detects the spinal cord position and orientation by using the elliptical Hough transform on multiple adjacent axial slices to produce an initial tubular mesh. Second, a low-resolution deformable model is iteratively propagated along the spinal cord. To deal with highly variable contrast levels between the spinal cord and the cerebrospinal fluid, the deformation is coupled with a contrast adaptation at each iteration. Third, a refinement process and a global deformation are applied on the low-resolution mesh to provide an accurate segmentation of the spinal cord. Our method was evaluated against a semi-automatic edge-based snake method implemented in ITK-SNAP (with heavy manual adjustment) by computing the 3D Dice coefficient, mean and maximum distance errors. Accuracy and robustness were assessed from 8 healthy subjects. Each subject had two volumes: one at the cervical and one at the thoracolumbar region. Results show a precision of 0.30 +/- 0.05 mm (mean absolute distance error) in the cervical region and 0.27 +/- 0.06 mm in the thoracolumbar region. The 3D Dice coefficient was of 0.93 for both regions.

Involvement of peripheral and spinal tumor necrosis factor α in spinal cord hyperexcitability during knee joint inflammation in rats.

PubMed

König, Christian; Zharsky, Maxim; Möller, Christian; Schaible, Hans-Georg; Ebersberger, Andrea

2014-03-01

Tumor necrosis factor α (TNFα) is produced not only in peripheral tissues, but also in the spinal cord. The purpose of this study was to address the potential of peripheral and spinal TNFα to induce and maintain spinal hyperexcitability, which is a hallmark of pain states in the joints during rheumatoid arthritis and osteoarthritis. In vivo recordings of the responses of spinal cord neurons to nociceptive knee input under normal conditions and in the presence of experimental knee joint inflammation were obtained in anesthetized rats. TNFα, etanercept, or antibodies to TNF receptors were applied to either the knee joint or the spinal cord surface. Injection of TNFα into the knee joint cavity increased the responses of spinal cord neurons to mechanical joint stimulation, and injection of etanercept into the knee joint reduced the inflammation-evoked spinal activity. These spinal effects closely mirrored the induction and reduction of peripheral sensitization. Responses to joint stimulation were also enhanced by spinal application of TNFα, and spinal application of either etanercept or anti-TNF receptor type I significantly attenuated the generation of inflammation-evoked spinal hyperexcitability, which is characterized by widespread pain sensitization beyond the inflamed joint. Spinally applied etanercept did not reduce established hyperexcitability in the acute kaolin/carrageenan model. In antigen-induced arthritis, etanercept decreased spinal responses on day 1, but not on day 3. While peripheral TNFα increases spinal responses to joint stimulation, spinal TNFα supports the generation of the full pattern of spinal hyperexcitability. However, established spinal hyperexcitability may be maintained by downstream mechanisms that are independent of spinal TNFα. Copyright © 2014 by the American College of Rheumatology.

The spinal cord dura mater reaction to nitinol and titanium alloy particles: a 1-year study in rabbits

PubMed Central

Rhalmi, Souad; Charette, Sylvie; Assad, Michel; Coillard, Christine

2007-01-01

This investigation was undertaken to simulate in an animal model the particles released from a porous nitinol interbody fusion device and to evaluate its consequences on the dura mater, spinal cord and nerve roots, lymph nodes (abdominal para-aortic), and organs (kidneys, spleen, pancreas, liver, and lungs). Our objective was to evaluate the compatibility of the nitinol particles with the dura mater in comparison with titanium alloy. In spite of the great use of metallic devices in spine surgery, the proximity of the spinal cord to the devices raised concerns about the effect of the metal debris that might be released onto the neural tissue. Forty-five New Zealand white female rabbits were divided into three groups: nitinol (treated: N = 4 per implantation period), titanium (treated: N = 4 per implantation period), and sham rabbits (control: N = 1 per observation period). The nitinol and titanium alloy particles were implanted in the spinal canal on the dura mater at the lumbar level L2–L3. The rabbits were sacrificed at 1, 4, 12, 26, and 52 weeks. Histologic sections from the regional lymph nodes, organs, from remote and implantation sites, were analyzed for any abnormalities and inflammation. Regardless of the implantation time, both nitinol and titanium particles remained at the implantation site and clung to the spinal cord lining soft tissue of the dura mater. The inflammation was limited to the epidural space around the particles and then reduced from acute to mild chronic during the follow-up. The dura mater, sub-dural space, nerve roots, and the spinal cord were free of reaction. No particles or abnormalities were found either in the lymph nodes or in the organs. In contact with the dura, the nitinol elicits an inflammatory response similar to that of titanium. The tolerance of nitinol by a sensitive tissue such as the dura mater during the span of 1 year of implantation demonstrated the safety of nitinol and its potential use as an intervertebral fusion device. PMID:17334794

A musculoskeletal model of the upper extremity for use in the development of neuroprosthetic systems

PubMed Central

Blana, Dimitra; Hincapie, Juan G.; Chadwick, Edward K.; Kirsch, Robert F.

2008-01-01

Upper extremity neuroprostheses use functional electrical stimulation (FES) to restore arm motor function to individuals with cervical level spinal cord injury. For the design and testing of these systems, a biomechanical model of the shoulder and elbow has been developed, to be used as a substitute for the human arm. It can be used to design and evaluate specific implementations of FES systems, as well as FES controllers. The model can be customized to simulate a variety of pathological conditions. For example, by adjusting the maximum force the muscles can produce, the model can be used to simulate an individual with tetraplegia and to explore the effects of FES of different muscle sets. The model comprises six bones, five joints, nine degrees of freedom, and 29 shoulder and arm muscles. It was developed using commercial, graphics-based modeling and simulation packages that are easily accessible to other researchers and can be readily interfaced to other analysis packages. It can be used for both forward-dynamic (inputs: muscle activation and external load; outputs:motions) and inverse-dynamic (inputs: motions and external load; outputs: muscle activation) simulations. Our model was verified by comparing the model-calculated muscle activations to electromyographic signals recorded from shoulder and arm muscles of five subjects. As an example of its application to neuroprosthesis design, the model was used to demonstrate the importance of rotator cuff muscle stimulation when aiming to restore humeral elevation. It is concluded that this model is a useful tool in the development and implementation of upper extremity neuroprosthetic systems. PMID:18420213

A musculoskeletal model of the upper extremity for use in the development of neuroprosthetic systems.

PubMed

Blana, Dimitra; Hincapie, Juan G; Chadwick, Edward K; Kirsch, Robert F

2008-01-01

Upper extremity neuroprostheses use functional electrical stimulation (FES) to restore arm motor function to individuals with cervical level spinal cord injury. For the design and testing of these systems, a biomechanical model of the shoulder and elbow has been developed, to be used as a substitute for the human arm. It can be used to design and evaluate specific implementations of FES systems, as well as FES controllers. The model can be customized to simulate a variety of pathological conditions. For example, by adjusting the maximum force the muscles can produce, the model can be used to simulate an individual with tetraplegia and to explore the effects of FES of different muscle sets. The model comprises six bones, five joints, nine degrees of freedom, and 29 shoulder and arm muscles. It was developed using commercial, graphics-based modeling and simulation packages that are easily accessible to other researchers and can be readily interfaced to other analysis packages. It can be used for both forward-dynamic (inputs: muscle activation and external load; outputs: motions) and inverse-dynamic (inputs: motions and external load; outputs: muscle activation) simulations. Our model was verified by comparing the model calculated muscle activations to electromyographic signals recorded from shoulder and arm muscles of five subjects. As an example of its application to neuroprosthesis design, the model was used to demonstrate the importance of rotator cuff muscle stimulation when aiming to restore humeral elevation. It is concluded that this model is a useful tool in the development and implementation of upper extremity neuroprosthetic systems.

Directing Spinal Cord Plasticity: The Impact of Stretch Therapy on Functional Recovery after Spinal Cord Injury

DTIC Science & Technology

2014-10-01

atrophy. Interestingly, there is a clinical phenomenon that stretching can lead to muscle fiber hypertrophy , but that doesn’t appear to be...specific muscle groups) on functional recovery after spinal cord injury in a rat model. We have undertaken these studies because of an observation we...spinal cord injury, locomotor recovery, physical therapy, muscle stretch, joint range- of-motion, rat. Overall Project Summary: In this, the

Biomechanical Evaluation of a Novel Apatite-Wollastonite Ceramic Cage Design for Lumbar Interbody Fusion: A Finite Element Model Study

PubMed Central

Şenköylü, Alpaslan; Aktaş, Erdem; Sarıkaya, Baran; Sipahioğlu, Serkan; Gürbüz, Rıza; Timuçin, Muharrem

2018-01-01

Objectives Cage design and material properties play a crucial role in the long-term results, since interbody fusions using intervertebral cages have become one of the basic procedures in spinal surgery. Our aim is to design a novel Apatite-Wollastonite interbody fusion cage and evaluate its biomechanical behavior in silico in a segmental spinal model. Materials and Methods Mechanical properties for the Apatite-Wollastonite bioceramic cages were obtained by fitting finite element results to the experimental compression behavior of a cage prototype. The prototype was made from hydroxyapatite, pseudowollastonite, and frit by sintering. The elastic modulus of the material was found to be 32 GPa. Three intact lumbar vertebral segments were modelled with the ANSYS 12.0.1 software and this model was modified to simulate a Posterior Lumbar Interbody Fusion. Four cage designs in different geometries were analyzed in silico under axial loading, flexion, extension, and lateral bending. Results The K2 design had the best overall biomechanical performance for the loads considered. Maximum cage stress recorded was 36.7 MPa in compression after a flexion load, which was within the biomechanical limits of the cage. Conclusion Biomechanical analyses suggest that K2 bioceramic cage is an optimal design and reveals essential material properties for a stable interbody fusion. PMID:29581974

Descending serotonergic facilitation mediated by spinal 5-HT3 receptors engages spinal rapamycin-sensitive pathways in the rat

PubMed Central

Asante, Curtis O.; Dickenson, Anthony H.

2010-01-01

We have recently reported the importance of spinal rapamycin-sensitive pathways in maintaining persistent pain-like states. A descending facilitatory drive mediated through spinal 5-HT3 receptors (5-HT3Rs) originating from superficial dorsal horn NK1-expressing neurons and that relays through the parabrachial nucleus and the rostroventral medial medulla to act on deep dorsal horn neurons is known be important in maintaining these pain-like states. To determine if spinal rapamycin-sensitive pathways are activated by a descending serotonergic drive, we investigated the effects of spinally administered rapamycin on responses of deep dorsal horn neurons that had been pre-treated with the selective 5-HT3R antagonist ondansetron. We also investigated the effects of spinally administered cell cycle inhibitor (CCI)-779 (a rapamycin ester analogue) on deep dorsal horn neurons from rats with carrageenan-induced inflammation of the hind paw. Unlike some other models of persistent pain, this model does not involve an altered 5-HT3R-mediated descending serotonergic drive. We found that the inhibitory effects of rapamycin were significantly reduced for neuronal responses to mechanical and thermal stimuli when the spinal cord was pre-treated with ondansetron. Furthermore, CCI-779 was found to be ineffective in attenuating spinal neuronal responses to peripheral stimuli in carrageenan-treated rats. Therefore, we conclude that 5-HT3R-mediated descending facilitation is one requirement for activation of rapamycin-sensitive pathways that contribute to persistent pain-like states. PMID:20709148

Computer-assisted design and finite element simulation of braces for the treatment of adolescent idiopathic scoliosis using a coronal plane radiograph and surface topography.

PubMed

Pea, Rany; Dansereau, Jean; Caouette, Christiane; Cobetto, Nikita; Aubin, Carl-Éric

2018-05-01

Orthopedic braces made by Computer-Aided Design and Manufacturing and numerical simulation were shown to improve spinal deformities correction in adolescent idiopathic scoliosis while using less material. Simulations with BraceSim (Rodin4D, Groupe Lagarrigue, Bordeaux, France) require a sagittal radiograph, not always available. The objective was to develop an innovative modeling method based on a single coronal radiograph and surface topography, and assess the effectiveness of braces designed with this approach. With a patient coronal radiograph and a surface topography, the developed method allowed the 3D reconstruction of the spine, rib cage and pelvis using geometric models from a database and a free form deformation technique. The resulting 3D reconstruction converted into a finite element model was used to design and simulate the correction of a brace. The developed method was tested with data from ten scoliosis cases. The simulated correction was compared to analogous simulations performed with a 3D reconstruction built using two radiographs and surface topography (validated gold standard reference). There was an average difference of 1.4°/1.7° for the thoracic/lumbar Cobb angle, and 2.6°/5.5° for the kyphosis/lordosis between the developed reconstruction method and the reference. The average difference of the simulated correction was 2.8°/2.4° for the thoracic/lumbar Cobb angles and 3.5°/5.4° the kyphosis/lordosis. This study showed the feasibility to design and simulate brace corrections based on a new modeling method with a single coronal radiograph and surface topography. This innovative method could be used to improve brace designs, at a lesser radiation dose for the patient. Copyright © 2018 Elsevier Ltd. All rights reserved.

Can the human lumbar posterior columns be stimulated by transcutaneous spinal cord stimulation? A modeling study

PubMed Central

Danner, Simon M.; Hofstoetter, Ursula S.; Ladenbauer, Josef; Rattay, Frank; Minassian, Karen

2014-01-01

Stimulation of different spinal cord segments in humans is a widely developed clinical practice for modification of pain, altered sensation and movement. The human lumbar cord has become a target for modification of motor control by epidural and more recently by transcutaneous spinal cord stimulation. Posterior columns of the lumbar spinal cord represent a vertical system of axons and when activated can add other inputs to the motor control of the spinal cord than stimulated posterior roots. We used a detailed three-dimensional volume conductor model of the torso and the McIntyre-Richard-Grill axon model to calculate the thresholds of axons within the posterior columns in response to transcutaneous lumbar spinal cord stimulation. Superficially located large diameter posterior column fibers with multiple collaterals have a threshold of 45.4 V, three times higher than posterior root fibers (14.1 V). With the stimulation strength needed to activate posterior column axons, posterior root fibers of large and small diameters as well as anterior root fibers are co-activated. The reported results inform on these threshold differences, when stimulation is applied to the posterior structures of the lumbar cord at intensities above the threshold of large-diameter posterior root fibers. PMID:21401670

Real-time advanced spinal surgery via visible patient model and augmented reality system.

PubMed

Wu, Jing-Ren; Wang, Min-Liang; Liu, Kai-Che; Hu, Ming-Hsien; Lee, Pei-Yuan

2014-03-01

This paper presents an advanced augmented reality system for spinal surgery assistance, and develops entry-point guidance prior to vertebroplasty spinal surgery. Based on image-based marker detection and tracking, the proposed camera-projector system superimposes pre-operative 3-D images onto patients. The patients' preoperative 3-D image model is registered by projecting it onto the patient such that the synthetic 3-D model merges with the real patient image, enabling the surgeon to see through the patients' anatomy. The proposed method is much simpler than heavy and computationally challenging navigation systems, and also reduces radiation exposure. The system is experimentally tested on a preoperative 3D model, dummy patient model and animal cadaver model. The feasibility and accuracy of the proposed system is verified on three patients undergoing spinal surgery in the operating theater. The results of these clinical trials are extremely promising, with surgeons reporting favorably on the reduced time of finding a suitable entry point and reduced radiation dose to patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Biomechanical testing of a polymer-based biomaterial for the restoration of spinal stability after nucleotomy

PubMed Central

Hegewald, Aldemar A; Knecht, Sven; Baumgartner, Daniel; Gerber, Hans; Endres, Michaela; Kaps, Christian; Stüssi, Edgar; Thomé, Claudius

2009-01-01

Background Surgery for disc herniations can be complicated by two major problems: painful degeneration of the spinal segment and re-herniation. Therefore, we examined an absorbable poly-glycolic acid (PGA) biomaterial, which was lyophilized with hyaluronic acid (HA), for its utility to (a) re-establish spinal stability and to (b) seal annulus fibrosus defects. The biomechanical properties range of motion (ROM), neutral zone (NZ) and a potential annulus sealing capacity were investigated. Methods Seven bovine, lumbar spinal units were tested in vitro for ROM and NZ in three consecutive stages: (a) intact, (b) following nucleotomy and (c) after insertion of a PGA/HA nucleus-implant. For biomechanical testing, spinal units were mounted on a loading-simulator for spines. In three cycles, axial loading was applied in an excentric mode with 0.5 Nm steps until an applied moment of ± 7.5 Nm was achieved in flexion/extension. ROM and NZ were assessed. These tests were performed without and with annulus sealing by sewing a PGA/HA annulus-implant into the annulus defect. Results Spinal stability was significantly impaired after nucleotomy (p < 0.001). Intradiscal implantation of a PGA-HA nucleus-implant, however, restored spinal stability (p < 0.003). There was no statistical difference between the stability provided by the nucleus-implant and the intact stage regarding flexion/extension movements (p = 0.209). During the testing sequences, herniation of biomaterial through the annulus defect into the spinal canal regularly occurred, resulting in compression of neural elements. Sewing a PGA/HA annulus-implant into the annulus defect, however, effectively prevented herniation. Conclusion PGA/HA biomaterial seems to be well suited for cell-free and cell-based regenerative treatment strategies in spinal surgery. Its abilities to restore spinal stability and potentially close annulus defects open up new vistas for regenerative approaches to treat intervertebral disc degeneration and for preventing implant herniation. PMID:19604373

Effect of electrical stimulation on neural regeneration via the p38-RhoA and ERK1/2-Bcl-2 pathways in spinal cord-injured rats

PubMed Central

Joo, Min Cheol; Jang, Chul Hwan; Park, Jong Tae; Choi, Seung Won; Ro, Seungil; Kim, Min Seob; Lee, Moon Young

2018-01-01

Although electrical stimulation is therapeutically applied for neural regeneration in patients, it remains unclear how electrical stimulation exerts its effects at the molecular level on spinal cord injury (SCI). To identify the signaling pathway involved in electrical stimulation improving the function of injured spinal cord, 21 female Sprague-Dawley rats were randomly assigned to three groups: control (no surgical intervention, n = 6), SCI (SCI only, n = 5), and electrical simulation (ES; SCI induction followed by ES treatment, n = 10). A complete spinal cord transection was performed at the 10th thoracic level. Electrical stimulation of the injured spinal cord region was applied for 4 hours per day for 7 days. On days 2 and 7 post SCI, the Touch-Test Sensory Evaluators and the Basso-Beattie-Bresnahan locomotor scale were used to evaluate rat sensory and motor function. Somatosensory-evoked potentials of the tibial nerve of a hind paw of the rat were measured to evaluate the electrophysiological function of injured spinal cord. Western blot analysis was performed to measure p38-RhoA and ERK1/2-Bcl-2 pathways related protein levels in the injured spinal cord. Rat sensory and motor functions were similar between SCI and ES groups. Compared with the SCI group, in the ES group, the latencies of the somatosensory-evoked potential of the tibial nerve of rats were significantly shortened, the amplitudes were significantly increased, RhoA protein level was significantly decreased, protein gene product 9.5 expression, ERK1/2, p38, and Bcl-2 protein levels in the spinal cord were significantly increased. These data suggest that ES can promote the recovery of electrophysiological function of the injured spinal cord through regulating p38-RhoA and ERK1/2-Bcl-2 pathway-related protein levels in the injured spinal cord. PMID:29557386

Photothrombosis-induced Focal Ischemia as a Model of Spinal Cord Injury in Mice

PubMed Central

Zhang, Nannan; Ding, Shinghua

2015-01-01

Spinal cord injury (SCI) is a devastating clinical condition causing permanent changes in sensorimotor and autonomic functions of the spinal cord (SC) below the site of injury. The secondary ischemia that develops following the initial mechanical insult is a serious complication of the SCI and severely impairs the function and viability of surviving neuronal and non-neuronal cells in the SC. In addition, ischemia is also responsible for the growth of lesion during chronic phase of injury and interferes with the cellular repair and healing processes. Thus there is a need to develop a spinal cord ischemia model for studying the mechanisms of ischemia-induced pathology. Focal ischemia induced by photothrombosis (PT) is a minimally invasive and very well established procedure used to investigate the pathology of ischemia-induced cell death in the brain. Here, we describe the use of PT to induce an ischemic lesion in the spinal cord of mice. Following retro-orbital sinus injection of Rose Bengal, the posterior spinal vein and other capillaries on the dorsal surface of SC were irradiated with a green light resulting in the formation of a thrombus and thus ischemia in the affected region. Results from histology and immunochemistry studies show that PT-induced ischemia caused spinal cord infarction, loss of neurons and reactive gliosis. Using this technique a highly reproducible and relatively easy model of SCI in mice can be achieved that would serve the purpose of scientific investigations into the mechanisms of ischemia induced cell death as well as the efficacy of neuroprotective drugs. This model will also allow exploration of the pathological changes that occur following SCI in live mice like axonal degeneration and regeneration, neuronal and astrocytic Ca2+ signaling using two-photon microscopy. PMID:26274772

Relevant Anatomic and Morphological Measurements of the Rat Spine: Considerations for Rodent Models of Human Spine Trauma.

PubMed

Jaumard, Nicolas V; Leung, Jennifer; Gokhale, Akhilesh J; Guarino, Benjamin B; Welch, William C; Winkelstein, Beth A

2015-10-15

Basic science study measuring anatomical features of the cervical and lumbar spine in rat with normalized comparison with the human. The goal of this study is to comprehensively compare the rat and human cervical and lumbar spines to investigate whether the rat is an appropriate model for spine biomechanics investigations. Animal models have been used for a long time to investigate the effects of trauma, degenerative changes, and mechanical loading on the structure and function of the spine. Comparative studies have reported some mechanical properties and/or anatomical dimensions of the spine to be similar between various species. However, those studies are largely limited to the lumbar spine, and a comprehensive comparison of the rat and human spines is lacking. Spines were harvested from male Holtzman rats (n = 5) and were scanned using micro- computed tomography and digitally rendered in 3 dimensions to quantify the spinal bony anatomy, including the lateral width and anteroposterior depth of the vertebra, vertebral body, and spinal canal, as well as the vertebral body and intervertebral disc heights. Normalized measurements of the vertebra, vertebral body, and spinal canal of the rat were computed and compared with corresponding measurements from the literature for the human in the cervical and lumbar spinal regions. The vertebral dimensions of the rat spine vary more between spinal levels than in humans. Rat vertebrae are more slender than human vertebrae, but the width-to-depth axial aspect ratios are very similar in both species in both the cervical and lumbar regions, especially for the spinal canal. The similar spinal morphology in the axial plane between rats and humans supports using the rat spine as an appropriate surrogate for modeling axial and shear loading of the human spine.

MRI-based noninvasive measurement of intracranial compliance derived from the relationship between transcranial blood and cerebrospinal fluid flows: modeling vs. direct approach

NASA Astrophysics Data System (ADS)

Tain, Rong-Wen; Alperin, Noam

2008-03-01

Intracranial compliance (ICC) determines the ability of the intracranial space to accommodate increase in volume (e.g., brain swelling) without a large increase in intracranial pressure (ICP). Therefore, measurement of ICC is potentially important for diagnosis and guiding treatment of related neurological problems. Modeling based approach uses an assumed lumped-parameter model of the craniospinal system (CSS) (e.g., RCL circuit), with either the arterial or the net transcranial blood flow (arterial inflow minus venous outflow) as input and the cranio-spinal cerebrospinal fluid (CSF) flow as output. The phase difference between the output and input is then often used as a measure of ICC However, it is not clear whether there is a predetermined relationship between ICC and the phase difference between these waveforms. A different approach for estimation of ICC has been recently proposed. This approach estimates ICC from the ratio of the intracranial volume and pressure changes that occur naturally with each heartbeat. The current study evaluates the sensitivity of the phase-based and the direct approach to changes in ICC. An RLC circuit model of the cranio-spinal system is used to simulate the cranio-spinal CSF flow for 3 different ICC states using the transcranial blood flows measured by MRI phase contrast from healthy human subjects. The effect of the increase in the ICC on the magnitude and phase response is calculated from the system's transfer function. We observed that within the heart rate frequency range, changes in ICC predominantly affected the amplitude of CSF pulsation and less so the phases. The compliance is then obtained for the different ICC states using the direct approach. The measures of compliance calculated using the direct approach demonstrated the highest sensitivity for changes in ICC. This work explains why phase shift based measure of ICC is less sensitive than amplitude based measures such as the direct approach method.

The use of regression tree analysis for predicting the functional outcome following traumatic spinal cord injury.

PubMed

Facchinello, Yann; Beauséjour, Marie; Richard-Denis, Andreane; Thompson, Cynthia; Mac-Thiong, Jean-Marc

2017-10-25

Predicting the long-term functional outcome following traumatic spinal cord injury is needed to adapt medical strategies and to plan an optimized rehabilitation. This study investigates the use of regression tree for the development of predictive models based on acute clinical and demographic predictors. This prospective study was performed on 172 patients hospitalized following traumatic spinal cord injury. Functional outcome was quantified using the Spinal Cord Independence Measure collected within the first-year post injury. Age, delay prior to surgery and Injury Severity Score were considered as continuous predictors while energy of injury, trauma mechanisms, neurological level of injury, injury severity, occurrence of early spasticity, urinary tract infection, pressure ulcer and pneumonia were coded as categorical inputs. A simplified model was built using only injury severity, neurological level, energy and age as predictor and was compared to a more complex model considering all 11 predictors mentioned above The models built using 4 and 11 predictors were found to explain 51.4% and 62.3% of the variance of the Spinal Cord Independence Measure total score after validation, respectively. The severity of the neurological deficit at admission was found to be the most important predictor. Other important predictors were the Injury Severity Score, age, neurological level and delay prior to surgery. Regression trees offer promising performances for predicting the functional outcome after a traumatic spinal cord injury. It could help to determine the number and type of predictors leading to a prediction model of the functional outcome that can be used clinically in the future.

Risk factors of non-specific spinal pain in childhood.

PubMed

Szita, Julia; Boja, Sara; Szilagyi, Agnes; Somhegyi, Annamaria; Varga, Peter Pal; Lazary, Aron

2018-05-01

Non-specific spinal pain can occur at all ages and current evidence suggests that pediatric non-specific spinal pain is predictive for adult spinal conditions. A 5-year long, prospective cohort study was conducted to identify the lifestyle and environmental factors leading to non-specific spinal pain in childhood. Data were collected from school children aged 7-16 years, who were randomly selected from three different geographic regions in Hungary. The risk factors were measured with a newly developed patient-reported questionnaire (PRQ). The quality of the instrument was assessed by the reliability with the test-retest method. Test (N = 952) and validity (N = 897) datasets were randomly formed. Risk factors were identified with uni- and multivariate logistic regression models and the predictive performance of the final model was evaluated using the receiver operating characteristic (ROC) method. The final model was built up by seven risk factors for spinal pain for days; age > 12 years, learning or watching TV for more than 2 h/day, uncomfortable school-desk, sleeping problems, general discomfort and positive familiar medical history (χ 2  = 101.07; df = 8; p < 0.001). The probabilistic performance was confirmed with ROC analysis on the test and validation cohorts (AUC = 0.76; 0.71). A simplified risk scoring system showed increasing possibility for non-specific spinal pain depending on the number of the identified risk factors (χ 2  = 65.0; df = 4; p < 0.001). Seven significant risk factors of non-specific spinal pain in childhood were identified using the new, easy to use and reliable PRQ which makes it possible to stratify the children according to their individual risk. These slides can be retrieved under Electronic Supplementary Material.

Convection-enhanced delivery of a hydrophilic nitrosourea ameliorates deficits and suppresses tumor growth in experimental spinal cord glioma models.

PubMed

Ogita, Shogo; Endo, Toshiki; Sugiyama, Shinichiro; Saito, Ryuta; Inoue, Tomoo; Sumiyoshi, Akira; Nonaka, Hiroi; Kawashima, Ryuta; Sonoda, Yukihiko; Tominaga, Teiji

2017-05-01

Convection-enhanced delivery (CED) is a technique allowing local infusion of therapeutic agents into the central nervous system, circumventing the blood-brain or spinal cord barrier. To evaluate the utility of nimustine hydrochloride (ACNU) CED in controlling tumor progression in an experimental spinal cord glioma model. Toxicity studies were performed in 42 rats following the administration of 4 μl of ACNU CED into the mid-thoracic spinal cord at concentrations ranging from 0.1 to 10 mg/ml. Behavioral analyses and histological evaluations were performed to assess ACNU toxicity in the spinal cord. A survival study was performed in 32 rats following the implantation of 9 L cells into the T8 spinal cord. Seven days after the implantation, rats were assigned to four groups: ACNU CED (0.25 mg/ml; n = 8); ACNU intravenous (i.v.) (0.4 mg; n = 8); saline CED (n = 8); saline i.v. (n = 8). Hind limb movements were evaluated daily in all rats for 21 days. Tumor sizes were measured histologically. The maximum tolerated ACNU concentration was 0.25 mg/ml. Preservation of hind limb motor function and tumor growth suppression was observed in the ACNU CED (0.25 mg/ml) and ACNU i.v. groups. Antitumor effects were more prominent in the ACNU CED group especially in behavioral analyses (P < 0.05; log-rank test). ACNU CED had efficacy in controlling tumor growth and preserving neurological function in an experimental spinal cord tumor model. ACNU CED can be a viable treatment option for spinal cord high-grade glioma.

Design and testing of a controlled electromagnetic spinal cord impactor for use in large animal models of acute traumatic spinal cord injury.

PubMed

Petteys, Rory J; Spitz, Steven M; Syed, Hasan; Rice, R Andrew; Sarabia-Estrada, Rachel; Goodwin, C Rory; Sciubba, Daniel M; Freedman, Brett A

2017-09-01

Spinal cord injury (SCI) causes debilitating neurological dysfunction and has been observed in warfighters injured in IED blasts. Clinical benefit of SCI treatment remains elusive and better large animal models are needed to assess treatment options. Here, we describe a controlled electromagnetic spinal cord impactor for use in large animal models of SCI. A custom spinal cord impactor and platform were fabricated for large animals (e.g., pig, sheep, dog, etc.). Impacts were generated by a voice coil actuator; force and displacement were measured with a load cell and potentiometer respectively. Labview (National Instruments, Austin, TX) software was used to control the impact cycle and import force and displacement data. Software finite impulse response (FIR) filtering was employed for all input data. Silicon tubing was used a surrogate for spinal cord in order to test the device; repeated impacts were performed at 15, 25, and 40 Newtons. Repeated impacts demonstrated predictable results at each target force. The average duration of impact was 71.2 ±6.1ms. At a target force of 40N, the output force was 41.5 ±0.7N. With a target of 25N, the output force was 23.5 ±0.6N; a target of 15Newtons revealed an output force of 15.2 ±1.4N. The calculated acceleration range was 12.5-21.2m/s 2 . This custom spinal cord impactor reliably delivers precise impacts to the spinal cord and will be utilized in future research to study acute traumatic SCI in a large animal. Published by Elsevier Ltd.

Thoracolumbar spinal ligaments exhibit negative and transverse pre-strain.

PubMed

Robertson, Daniel J; Von Forell, Gregory A; Alsup, Jeremy; Bowden, Anton E

2013-07-01

The present work represents the first reported bi-axial spinal ligament pre-strain data for the thoracic and lumbar spine. Ligament pre-strain (in-situ strain) is known to significantly alter joint biomechanics. However, there is currently a lack of comprehensive data with regards to spinal ligament pre-strain. The current work determined the pre-strain of 71 spinal ligaments (30 anterior longitudinal ligaments, 27 supraspinous ligaments and 14 interspinous ligaments). The interspinous ligament and the anterior longitudinal ligament exhibited bi-axial pre-strain distributions, demonstrating they are not uniaxial structures. The supraspinous ligament frequently exhibited large amounts of negative pre-strain or laxity suggesting it makes no mechanical contribution to spinal stability near the neutral posture. Upon implementing multi-axial pre-strain results into a finite element model of the lumbar spine, large differences in spinal biomechanics were observed. These results demonstrate the necessity of accounting for ligament pre-strain in biomechanical models. In addition, the authors present a unique experimental method for obtaining ligament pre-strain that presents a number of advantages when compared to standard techniques. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of Local Administration of Boric Acid on Posterolateral Spinal Fusion with Autogenous Bone Grafting in a Rodent Model.

PubMed

Kömürcü, Erkam; Özyalvaçlı, Gülzade; Kaymaz, Burak; Gölge, Umut Hatay; Göksel, Ferdi; Cevizci, Sibel; Adam, Gürhan; Ozden, Raif

2015-09-01

Spinal fusion is among the most frequently applied spinal surgical procedures. The goal of the present study was to evaluate whether the local administration of boric acid (BA) improves spinal fusion in an experimental spinal fusion model in rats. Currently, there is no published data that evaluates the possible positive effects if the local administration of BA on posterolateral spinal fusion. Thirty-two rats were randomly divided into four independent groups: no material was added at the fusion area for group 1; an autogenous morselized corticocancellous bone graft was used for group 2; an autogenous morselized corticocancellous bone graft with boric acid (8.7 mg/kg) for group 3; and only boric acid was placed into the fusion area for group 4. The L4-L6 spinal segments were collected at week 6, and the assessments included radiography, manual palpation, and histomorphometry. A statistically significant difference was determined between the groups with regard to the mean histopathological scores (p = 0.002), and a paired comparison was made with the Mann-Whitney U test to detect the group/groups from which the difference originated. It was determined that only the graft + BA practice increased the histopathological score significantly with regard to the control group (p = 0.002). Whereas, there was no statistically significant difference between the groups in terms of the manual assessment of fusion and radiographic analysis (respectively p = 0.328 and p = 0.196). This preliminary study suggests that BA may clearly be useful as a therapeutic agent in spinal fusion. However, further research is required to show the most effective dosage of BA on spinal fusion, and should indicate whether BA effects spinal fusion in the human body.

Role of cranial and spinal virtual and augmented reality simulation using immersive touch modules in neurosurgical training.

PubMed

Alaraj, Ali; Charbel, Fady T; Birk, Daniel; Tobin, Matthew; Tobin, Mathew; Luciano, Cristian; Banerjee, Pat P; Rizzi, Silvio; Sorenson, Jeff; Foley, Kevin; Slavin, Konstantin; Roitberg, Ben

2013-01-01

Recent studies have shown that mental script-based rehearsal and simulation-based training improve the transfer of surgical skills in various medical disciplines. Despite significant advances in technology and intraoperative techniques over the last several decades, surgical skills training on neurosurgical operations still carries significant risk of serious morbidity or mortality. Potentially avoidable technical errors are well recognized as contributing to poor surgical outcome. Surgical education is undergoing overwhelming change, as a result of the reduction of work hours and current trends focusing on patient safety and linking reimbursement with clinical outcomes. Thus, there is a need for adjunctive means for neurosurgical training, which is a recent advancement in simulation technology. ImmersiveTouch is an augmented reality system that integrates a haptic device and a high-resolution stereoscopic display. This simulation platform uses multiple sensory modalities, re-creating many of the environmental cues experienced during an actual procedure. Modules available include ventriculostomy, bone drilling, percutaneous trigeminal rhizotomy, and simulated spinal modules such as pedicle screw placement, vertebroplasty, and lumbar puncture. We present our experience with the development of such augmented reality neurosurgical modules and the feedback from neurosurgical residents.

Role of Cranial and Spinal Virtual and Augmented Reality Simulation Using Immersive Touch Modules in Neurosurgical Training

PubMed Central

Alaraj, Ali; Charbel, Fady T.; Birk, Daniel; Tobin, Mathew; Luciano, Cristian; Banerjee, Pat P.; Rizzi, Silvio; Sorenson, Jeff; Foley, Kevin; Slavin, Konstantin; Roitberg, Ben

2013-01-01

Recent studies have shown that mental script-based rehearsal and simulation-based training improves the transfer of surgical skills in various medical disciplines. Despite significant advances in technology and intraoperative techniques over the last several decades, surgical skills training on neurosurgical operations still carries significant risk of serious morbidity or mortality. Potentially avoidable technical errors are well recognized as contributing to poor surgical outcome. Surgical education is undergoing overwhelming change, with reduction of working hours and current trends to focus on patient’s safety and linking reimbursement with clinical outcomes, and there is a need for adjunctive means for neurosurgical training;this has been recent advancement in simulation technology. ImmersiveTouch (IT) is an augmented reality (AR) system that integrates a haptic device and a high-resolution stereoscopic display. This simulation platform utilizes multiple sensory modalities, recreating many of the environmental cues experienced during an actual procedure. Modules available include ventriculostomy, bone drilling, percutaneous trigeminal rhizotomy, in addition to simulated spinal modules such as pedicle screw placement, vertebroplasty, and lumbar puncture. We present our experience with development of such AR neurosurgical modules and the feedback from neurosurgical residents. PMID:23254799

Artificial Gravity as a Countermeasure of Cardiovascular Deconditioning in Spinal Cord Injury

NASA Technical Reports Server (NTRS)

Cardus, David

1999-01-01

An essential item in the development of this project was the availability of the artificial gravity simulator (AGS). At the termination of that grant in 1994, the AGS was dismantled and transferred to NASA Johnson Space Center. It took over two years for the AGS to be re-assembled and re-certified for use. As a consequence of the non-availability of the AGS for two years, there was a considerable delay in implementing the various phases of the project. The subjects involved in the study were eight healthy able bodied subjects and twelve with spinal cord injury. After analysis of the data collected on these subjects, six of the healthy able bodied subjects and three of the sub ects with spinal cord injury were found to qualify for the study. This report gives the results of four subjects only, two healthy able bodied and two spinal cord injured subjects because the period of the grant (1 year) and its extension (1 year) expired before additional subjects could be studied. The principal objective of the study was to conduct a series of experiments to demonstrate the feasibility of utilizing artificial gravity to assist in the physical rehabilitation of persons with spinal cord injuries.

Spinal decompression sickness: mechanical studies and a model.

PubMed

Hills, B A; James, P B

1982-09-01

Six experimental investigations of various mechanical aspects of the spinal cord are described relevant to its injury by gas deposited from solution by decompression. These show appreciable resistances to gas pockets dissipating by tracking along tissue boundaries or distending tissue, the back pressure often exceeding the probable blood perfusion pressure--particularly in the watershed zones. This leads to a simple mechanical model of spinal decompression sickness based on the vascular "waterfall" that is consistent with the pathology, the major quantitative aspects, and the symptomatology--especially the reversibility with recompression that is so difficult to explain by an embolic mechanism. The hypothesis is that autochthonous gas separating from solution in the spinal cord can reach sufficient local pressure to exceed the perfusion pressure and thus occlude blood flow.

Neutron equivalent doses and associated lifetime cancer incidence risks for head & neck and spinal proton therapy

NASA Astrophysics Data System (ADS)

Athar, Basit S.; Paganetti, Harald

2009-08-01

In this work we have simulated the absorbed equivalent doses to various organs distant to the field edge assuming proton therapy treatments of brain or spine lesions. We have used computational whole-body (gender-specific and age-dependent) voxel phantoms and considered six treatment fields with varying treatment volumes and depths. The maximum neutron equivalent dose to organs near the field edge was found to be approximately 8 mSv Gy-1. We were able to clearly demonstrate that organ-specific neutron equivalent doses are age (stature) dependent. For example, assuming an 8-year-old patient, the dose to brain from the spinal fields ranged from 0.04 to 0.10 mSv Gy-1, whereas the dose to the brain assuming a 9-month-old patient ranged from 0.5 to 1.0 mSv Gy-1. Further, as the field aperture opening increases, the secondary neutron equivalent dose caused by the treatment head decreases, while the secondary neutron equivalent dose caused by the patient itself increases. To interpret the dosimetric data, we analyzed second cancer incidence risks for various organs as a function of patient age and field size based on two risk models. The results show that, for example, in an 8-year-old female patient treated with a spinal proton therapy field, breasts, lungs and rectum have the highest radiation-induced lifetime cancer incidence risks. These are estimated to be 0.71%, 1.05% and 0.60%, respectively. For an 11-year-old male patient treated with a spinal field, bronchi and rectum show the highest risks of 0.32% and 0.43%, respectively. Risks for male and female patients increase as their age at treatment time decreases.

The circulation of the cerebrospinal fluid (CSF) in the spinal canal

NASA Astrophysics Data System (ADS)

Sanchez, Antonio L.; Martinez-Bazan, Carlos; Lasheras, Juan C.

2016-11-01

Cerebrospinal Fluid (CSF) is secreted in the choroid plexus in the lateral sinuses of the brain and fills the subarachnoid space bathing the external surfaces of the brain and the spinal canal. Absence of CSF circulation has been shown to impede its physiological function that includes, among others, supplying nutrients to neuronal and glial cells and removing the waste products of cellular metabolism. Radionuclide scanning images published by Di Chiro in 1964 showed upward migration of particle tracers from the lumbar region of the spinal canal, thereby suggesting the presence of an active bulk circulation responsible for bringing fresh CSF into the spinal canal and returning a portion of it to the cranial vault. However, the existence of this slow moving bulk circulation in the spinal canal has been a subject of dispute for the last 50 years. To date, there has been no physical explanation for the mechanism responsible for the establishment of such a bulk motion. We present a perturbation analysis of the flow in an idealized model of the spinal canal and show how steady streaming could be responsible for the establishment of such a circulation. The results of this analysis are compared to flow measurements conducted on in-vitro models of the spinal canal of adult humans.

Histopathologic correlation of magnetic resonance imaging signal patterns in a spinal cord injury model.

PubMed

Weirich, S D; Cotler, H B; Narayana, P A; Hazle, J D; Jackson, E F; Coupe, K J; McDonald, C L; Langford, L A; Harris, J H

1990-07-01

Magnetic resonance imaging (MRI) provides a noninvasive method of monitoring the pathologic response to spinal cord injury. Specific MR signal intensity patterns appear to correlate with degrees of improvement in the neurologic status in spinal cord injury patients. Histologic correlation of two types of MR signal intensity patterns are confirmed in the current study using a rat animal model. Adult male Sprague-Dawley rats underwent spinal cord trauma at the midthoracic level using a weight-dropping technique. After laminectomy, 5- and 10-gm brass weights were dropped from designated heights onto a 0.1-gm impounder placed on the exposed dura. Animals allowed to regain consciousness demonstrated variable recovery of hind limb paraplegia. Magnetic resonance images were obtained from 2 hours to 1 week after injury using a 2-tesla MRI/spectrometer. Sacrifice under anesthesia was performed by perfusive fixation; spinal columns were excised en bloc, embedded, sectioned, and observed with the compound light microscope. Magnetic resonance axial images obtained during the time sequence after injury demonstrate a distinct correlation between MR signal intensity patterns and the histologic appearance of the spinal cord. Magnetic resonance imaging delineates the pathologic processes resulting from acute spinal cord injury and can be used to differentiate the type of injury and prognosis.

Kainate and metabolic perturbation mimicking spinal injury differentially contribute to early damage of locomotor networks in the in vitro neonatal rat spinal cord.

PubMed

Taccola, G; Margaryan, G; Mladinic, M; Nistri, A

2008-08-13

Acute spinal cord injury evolves rapidly to produce secondary damage even to initially spared areas. The result is loss of locomotion, rarely reversible in man. It is, therefore, important to understand the early pathophysiological processes which affect spinal locomotor networks. Regardless of their etiology, spinal lesions are believed to include combinatorial effects of excitotoxicity and severe stroke-like metabolic perturbations. To clarify the relative contribution by excitotoxicity and toxic metabolites to dysfunction of locomotor networks, spinal reflexes and intrinsic network rhythmicity, we used, as a model, the in vitro thoraco-lumbar spinal cord of the neonatal rat treated (1 h) with either kainate or a pathological medium (containing free radicals and hypoxic/aglycemic conditions), or their combination. After washout, electrophysiological responses were monitored for 24 h and cell damage analyzed histologically. Kainate suppressed fictive locomotion irreversibly, while it reversibly blocked neuronal excitability and intrinsic bursting induced by synaptic inhibition block. This result was associated with significant neuronal loss around the central canal. Combining kainate with the pathological medium evoked extensive, irreversible damage to the spinal cord. The pathological medium alone slowed down fictive locomotion and intrinsic bursting: these oscillatory patterns remained throughout without regaining their control properties. This phenomenon was associated with polysynaptic reflex depression and preferential damage to glial cells, while neurons were comparatively spared. Our model suggests distinct roles of excitotoxicity and metabolic dysfunction in the acute damage of locomotor networks, indicating that different strategies might be necessary to treat the various early components of acute spinal cord lesion.

Lumped Parameter Models of the Central Nervous System for VIIP Research

NASA Technical Reports Server (NTRS)

Vera, J.; Mulugeta, L.; Nelson, E. S.; Raykin, J.; Feola, A.; Gleason, R.; Samuels, B.; Myers, J. G.

2015-01-01

INTRODUCTION: Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit, such as to Mars and asteroids, expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome [1]. It has been hypothesized that the headward shift of cerebral spinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn induces VIIP syndrome through biomechanical pathways [1, 2]. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the realted IWS abstracts submitted by Nelson et al., Feola et al. and Ethier et al. METHODS: We have developed a nine compartment CNS model (Figure 1) capable of both time-dependent and steady state fluid transport simulations, based on the works of Stevens et al. [3]. The breakdown of compartments within the model includes: vascular (3), CSF (2), brain (1) and extracranial (3). The boundary pressure in the Central Arteries [A] node is prescribed using an oscillating pressure function PA(t) simulating the carotid pulsatile pressure wave as developed by Linninger et al. [4]. For each time step, pressures are integrated through time using an adaptive-timestep 4th and 5th order Runga-Kutta solver. Once pressures are found, constitutive equations are used to solve for flowrates (Q) between each compartment. In addition to fluid flow between the different compartments, compliance (C) interactions between neighboring compartments are represented. We are also developing a second CNS model based on the works of Linninger et al. [4] which takes a more granular approach to represent the interactions of the intracranial and spinal compartments with the inclusion of arteries, arterioles, capillaries, venules, veins, venous sinus, and ventricles. The flow through the arteries, veins and CSF compartments are governed by continuity, momentum and distensibility balance equations. Furthermore, unlike the Stevens et al. approach, the Monro-Kellie doctrine of constant cranial volume and the bi-phasic nature of the brain parenchyma are implemented. These features appear to be more consistent with the physiologic and anatomical behavior of the CNS, and follow a modeling philosophy similar to the lumped parameter eye model that is intended to be integrated with the CNS model. However, Linninger’s approach has never been implemented to include hydrostatic gradient and microgravity simulation capabilities. Therefore, we aim at implement this modeling approach for spaceflight simulations and assess its overall applicability to VIIP research. OBJECTIVES: We will present verification and validation test results for both models, as well as head-to-head comparison to explore their strengths and limitations with respect to mathematical implementation and physiological significance for VIIP research. In doing so, we hope to provide some guidance to the HRP research community on how to appropriately leverage lumped parameter models for space biomedical research.

Measurement Structure of the Trait Hope Scale in Persons with Spinal Cord Injury: A Confirmatory Factor Analysis

ERIC Educational Resources Information Center

Smedema, Susan Miller; Pfaller, Joseph; Moser, Erin; Tu, Wei-Mo; Chan, Fong

2013-01-01

Objective: To evaluate the measurement structure of the Trait Hope Scale (THS) among individuals with spinal cord injury. Design: Confirmatory factor analysis and reliability and validity analyses were performed. Participants: 242 individuals with spinal cord injury. Results: Results support the two-factor measurement model for the THS with agency…

Are there endogenous stem cells in the spinal cord?

PubMed

Ferrucci, Michela; Ryskalin, Larisa; Busceti, Carla L; Gaglione, Anderson; Biagioni, Francesca; Fornai, Francesco

2017-12-01

Neural progenitor cells (NPC) represent the stem-like niche of the central nervous system that maintains a regenerative potential also in the adult life. Despite NPC in the brain are well documented, the presence of NPC in the spinal cord has been controversial for a long time. This is due to a scarce activity of NPC within spinal cord, which also makes difficult their identification. The present review recapitulates the main experimental studies, which provided evidence for the occurrence of NPC within spinal cord, with a special emphasis on spinal cord injury and amyotrophic lateral sclerosis. By using experimental models, here we analyse the site-specificity, the phenotype and the main triggers of spinal cord NPC. Moreover, data are reported on the effect of specific neurogenic stimuli on these spinal cord NPC in an effort to comprehend the endogenous neurogenic potential of this stem cell niche.

Reduce, reuse, recycle - Developmental signals in spinal cord regeneration.

PubMed

Cardozo, Marcos Julian; Mysiak, Karolina S; Becker, Thomas; Becker, Catherina G

2017-12-01

Anamniotes, fishes and amphibians, have the capacity to regenerate spinal cord tissue after injury, generating new neurons that mature and integrate into the spinal circuitry. Elucidating the molecular signals that promote this regeneration is a fundamental question in regeneration research. Model systems, such as salamanders and larval and adult zebrafish are used to analyse successful regeneration. This shows that many developmental signals, such as Notch, Hedgehog (Hh), Bone Morphogenetic Protein (BMP), Wnt, Fibroblast Growth Factor (FGF), Retinoic Acid (RA) and neurotransmitters are redeployed during regeneration and activate resident spinal progenitor cells. Here we compare the roles of these signals in spinal cord development and regeneration of the much larger and fully patterned adult spinal cord. Understanding how developmental signalling systems are reactivated in successfully regenerating species may ultimately lead to ways to reactivate similar systems in mammalian progenitor cells, which do not show neurogenesis after spinal injury. Copyright © 2017. Published by Elsevier Inc.

Spinal subarachnoid space pressure measurements in an in vitro spinal stenosis model: implications on syringomyelia theories.

PubMed

Martin, Bryn A; Labuda, Richard; Royston, Thomas J; Oshinski, John N; Iskandar, Bermans; Loth, Francis

2010-11-01

Full explanation for the pathogenesis of syringomyelia (SM), a neuropathology characterized by the formation of a cystic cavity (syrinx) in the spinal cord (SC), has not yet been provided. It has been hypothesized that abnormal cerebrospinal fluid (CSF) pressure, caused by subarachnoid space (SAS) flow blockage (stenosis), is an underlying cause of syrinx formation and subsequent pain in the patient. However, paucity in detailed in vivo pressure data has made theoretical explanations for the syrinx difficult to reconcile. In order to understand the complex pressure environment, four simplified in vitro models were constructed to have anatomical similarities with post-traumatic SM and Chiari malformation related SM. Experimental geometry and properties were based on in vivo data and incorporated pertinent elements such as a realistic CSF flow waveform, spinal stenosis, syrinx, flexible SC, and flexible spinal column. The presence of a spinal stenosis in the SAS caused peak-to-peak cerebrospinal fluid CSF pressure fluctuations to increase rostral to the stenosis. Pressure with both stenosis and syrinx present was complex. Overall, the interaction of the syrinx and stenosis resulted in a diastolic valve mechanism and rostral tensioning of the SC. In all experiments, the blockage was shown to increase and dissociate SAS pressure, while the axial pressure distribution in the syrinx remained uniform. These results highlight the importance of the properties of the SC and spinal SAS, such as compliance and permeability, and provide data for comparison with computational models. Further research examining the influence of stenosis size and location, and the importance of tissue properties, is warranted.

Lumbar muscle inflammation alters spinally mediated locomotor recovery induced by training in a mouse model of complete spinal cord injury.

PubMed

Jeffrey-Gauthier, Renaud; Piché, Mathieu; Leblond, Hugues

2017-09-17

Locomotor networks after spinal cord injury (SCI) are shaped by training-activated proprioceptive and cutaneous inputs. Nociception from injured tissues may alter these changes but has largely been overlooked. The objective of the present study was to ascertain whether lumbar muscle inflammation hinders locomotion recovery in a mouse model of complete SCI. Lower limb kinematics during treadmill training was assessed before and after complete SCI at T8 (2, 7, 14, 21 and 28days post-injury). Locomotor recovery was compared in 4 groups of CD1 mice: control spinal mice; spinal mice with daily locomotor training; spinal mice with lumbar muscle inflammation (Complete Freund's Adjuvant (CFA) injection); and spinal mice with locomotor training and CFA. On day 28, H-reflex excitability and its inhibition at high-frequency stimulation (frequency-dependent depression: FDD) were compared between groups, all of which showed locomotor recovery. Recovery was enhanced by training, whereas lumbar muscle inflammation hindered these effects (knee angular excursion and paw drag: p's<0.05). In addition, lumbar muscle inflammation impaired hind limb coupling during locomotion (p<0.05) throughout recovery. Also, H-reflex disinhibition was prevented by training, with or without CFA injection (p's<0.05). Altogether, these results indicate that back muscle inflammation modulates spinally mediated locomotor recovery in mice with complete SCI, in part, by reducing adaptive changes induced by training. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

A neural hypothesis for stress-induced headache.

PubMed

Cathcart, Stuart

2009-12-01

The mechanisms by which stress contributes to CTH are not clearly understood. The commonly accepted notion of muscle hyper-reactivity to stress in CTH sufferers is not supported in the research data. We propose a neural model whereby stress acts supra-spinally to aggravate already increased pain sensitivity in CTH sufferers. Indirect support for the model comes from emerging research elucidating complex supra-spinal networks through which psychological stress may contribute to and even cause pain. Similarly, emerging research demonstrates supra-spinal pain processing abnormalities in CTH sufferers. While research with CTH sufferers offering direct support for the model is lacking at present, initial work by our group is consistent with the models predictions, particularly, that stress aggravates already increased pain sensitivity in CTH sufferers.

Real-time monitoring of spinal cord blood flow with a novel sensor mounted on a cerebrospinal fluid drainage catheter in an animal model.

PubMed

Hayatsu, Yukihiro; Kawamoto, Shunsuke; Matsunaga, Tadao; Haga, Yoichi; Saiki, Yoshikatsu

2014-10-01

The aim of our study was to develop a novel monitoring system for spinal cord blood flow (SCBF) to test the efficacy of the SCBF sensor in an animal model. The sensor system consisted of 2 optical fibers, a pedestal for fiber fixation, and a mirror for the laser reflection and was incorporated into a cerebrospinal fluid drainage catheter. In vivo studies were performed in a swine model (n=10) to measure SCBF during spinal cord ischemia induced by clamping the descending thoracic aorta and supra-aortic neck vessels, when necessary. A temporary low cardiac output model was also created by inflow clamping of the inferior vena cava to analyze the quantitative changes in SCBF during this maneuver. The developed SCBF monitoring catheter placed intrathecally could detect SCBF in all the swine. The SCBF after aortic crossclamping at the fourth intercostal level exhibited diverse changes reproducibly among the swine, with a >25% reduction in SCBF in 5 pigs, an increase in 3, and no significant changes in 2. Consistent reductions were recorded during inferior vena cava occlusion. The mean SCBF decreased by 32% after inferior vena cava occlusion when the cardiac output had decreased by 27%. We have developed a novel SCBF sensor that could detect real-time changes in spinal cord perfusion in a swine model. The device holds promise to detect imminent ischemia or ensure acceptable blood perfusion in the spinal cord and could further enhance our understanding of spinal cord circulation. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

A model for flexi-bar to evaluate intervertebral disc and muscle forces in exercises.

PubMed

Abdollahi, Masoud; Nikkhoo, Mohammad; Ashouri, Sajad; Asghari, Mohsen; Parnianpour, Mohamad; Khalaf, Kinda

2016-10-01

This study developed and validated a lumped parameter model for the FLEXI-BAR, a popular training instrument that provides vibration stimulation. The model which can be used in conjunction with musculoskeletal-modeling software for quantitative biomechanical analyses, consists of 3 rigid segments, 2 torsional springs, and 2 torsional dashpots. Two different sets of experiments were conducted to determine the model's key parameters including the stiffness of the springs and the damping ratio of the dashpots. In the first set of experiments, the free vibration of the FLEXI-BAR with an initial displacement at its end was considered, while in the second set, forced oscillations of the bar were studied. The properties of the mechanical elements in the lumped parameter model were derived utilizing a non-linear optimization algorithm which minimized the difference between the model's prediction and the experimental data. The results showed that the model is valid (8% error) and can be used for simulating exercises with the FLEXI-BAR for excitations in the range of the natural frequency. The model was then validated in combination with AnyBody musculoskeletal modeling software, where various lumbar disc, spinal muscles and hand muscles forces were determined during different FLEXI-BAR exercise simulations. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

Improving outcome of sensorimotor functions after traumatic spinal cord injury.

PubMed

Dietz, Volker

2016-01-01

In the rehabilitation of a patient suffering a spinal cord injury (SCI), the exploitation of neuroplasticity is well established. It can be facilitated through the training of functional movements with technical assistance as needed and can improve outcome after an SCI. The success of such training in individuals with incomplete SCI critically depends on the presence of physiological proprioceptive input to the spinal cord leading to meaningful muscle activations during movement performances. Some actual preclinical approaches to restore function by compensating for the loss of descending input to spinal networks following complete/incomplete SCI are critically discussed in this report. Electrical and pharmacological stimulation of spinal neural networks is still in the experimental stage, and despite promising repair studies in animal models, translations to humans up to now have not been convincing. It is possible that a combination of techniques targeting the promotion of axonal regeneration is necessary to advance the restoration of function. In the future, refinement of animal models according to clinical conditions and requirements may contribute to greater translational success.

Raman spectroscopic investigation of spinal cord injury in a rat model

NASA Astrophysics Data System (ADS)

Saxena, Tarun; Deng, Bin; Stelzner, Dennis; Hasenwinkel, Julie; Chaiken, Joseph

2011-02-01

Raman spectroscopy was used to study temporal molecular changes associated with spinal cord injury (SCI) in a rat model. Raman spectra of saline-perfused, injured, and healthy rat spinal cords were obtained and compared. Two injury models, a lateral hemisection and a moderate contusion were investigated. The net fluorescence and the Raman spectra showed clear differences between the injured and healthy spinal cords. Based on extensive histological and biochemical characterization of SCI available in the literature, these differences were hypothesized to be due to cell death, demyelination, and changes in the extracellular matrix composition, such as increased expression of proteoglycans and hyaluronic acid, at the site of injury where the glial scar forms. Further, analysis of difference spectra indicated the presence of carbonyl containing compounds, hypothesized to be products of lipid peroxidation and acid catalyzed hydrolysis of glycosaminoglycan moieties. These results compared well with in vitro experiments conducted on chondroitin sulfate sugars. Since the glial scar is thought to be a potent biochemical barrier to nerve regeneration, this observation suggests the possibility of using near infrared Raman spectroscopy to study injury progression and explore potential treatments ex vivo, and ultimately monitor potential remedial treatments within the spinal cord in vivo.

[Prostatic inflammation-induced chronic pelvic pain: Roles of substance P and c-fos in the spinal cord].

PubMed

Liu, Ying-jia; Song, Guo-hong; Zhang, Chen

2015-08-01

To explore the possible pain mechanism of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). The models of CP/CPPS were established in male Wistar rats by the autoimmune method. The paw withdrawal threshold (PWT) was detected using Von Frey filament. The expressions of the substance P and c-fos in the prostate and spinal L5-S2 segments were determined by immunohistochemistry followed by analysis of their correlation with CP/CPPS. Compared with the control rats, the CP/CPPS models showed significantly decreased PWT (P < 0.05), remarkable prostatic inflammation, enlarged scope of lesions, and obvious interstitial lymphocytic infiltration (P < 0.05). Both the expressions of substance P and c-fos were markedly elevated in the prostate and spinal dorsal horn (L5-S2) of the rat models (P < 0.05), but the expression of substance P in the prostate exhibited no correlation with that in the spinal cord (r = 0.099, P = 0.338), nor did that of c-fos (r = 0.027, P = 0.454). The upregulated expressions of substance P and c-fos in the spinal cord L5-S2 sections may be associated with the pain mechanism of CP/CPPS.

[The role of brain-derived neurotrophic factor in pain facilitation and spinal mechanism in rat model of bone cancer pain].

PubMed

Wang, Li-na; Yang, Jian-ping; Ji, Fu-hai; Wang, Xiu-yun; Zuo, Jian-ling; Xu, Qi-nian; Jia, Xiao-ming; Zhou, Jing; Ren, Chun-guang; Li, Wei

2011-05-10

To investigate the role of brain-derived neurotrophic factor (BDNF) in pain facilitation and spinal mechanisms in the rat model of bone cancer pain. The bone cancer pain model was developed by inoculated Walker 256 mammary gland carcinoma cells into the tibia medullary cavity. Sixty SD female rats were divided into 5 groups (n = 12 each) randomly; group I: control group (sham operation); group II: model group; group III: control group + anti-BDNF intrathecal (i.t.); group IV: model group + control IgG i.t.; group V: model group + anti-BDNF i.t.. Anti-BDNF or control IgG was injected i.t. during 7 to 9th day. Von-Frey threshold was measured one day before operation and every 2 days after operation. On the 9th day after threshold tested, rats were sacrificed after i.t. injection of either anti-BDNF or control IgG, the lumbar 4-6 spinal cord was removed. The expression of the spinal BDNF and the phosphorylation of extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) were detected by immunohistochemistry assay and Western-Blot. Co-expression pattern of BDNF and p-ERK1/2 were determined by double-labeling immunofluorescence. We demonstrated the coexistence of BDNF and p-ERK1/2 in the spinal cord of rats. From the 7 to 9th day after operation, von-Frey threshold in groups II and IV was significantly lower than that in group I and group V (P < 0.01), group V was remarkly higher than that in group IV (P < 0.01). The spinal BDNF and p-ERK1/2 expression in group II or IV were significantly increased compared with that in group I or V (P < 0.01), intrathecal anti-BDNF was significantly suppressed BDNF and p-ERK1/2 expression (P < 0.01). BDNF and p-ERK1/2 was coexistence in the spinal cord of rats, and it maybe involved in the bone cancer pain.

Validation of a Preclinical Spinal Safety Model: Effects of Intrathecal Morphine in the Neonatal Rat

PubMed Central

Westin, B. David; Walker, Suellen M.; Deumens, Ronald; Grafe, Marjorie; Yaksh, Tony L.

2010-01-01

Background Preclinical studies demonstrate increased neuroapoptosis after general anesthesia in early life. Neuraxial techniques may minimize potential risks, but there has been no systematic evaluation of spinal analgesic safety in developmental models. We aimed to validate a preclinical model for evaluating dose-dependent efficacy, spinal cord toxicity, and long term function following intrathecal morphine in the neonatal rat. Methods Lumbar intrathecal injections were performed in anesthetized rats aged postnatal day (P)3, 10 and 21. The relationship between injectate volume and segmental spread was assessed post mortem and by in-vivo imaging. To determine the antinociceptive dose, mechanical withdrawal thresholds were measured at baseline and 30 minutes following intrathecal morphine. To evaluate toxicity, doses up to the maximum tolerated were administered, and spinal cord histopathology, apoptosis and glial response were evaluated 1 and 7 days following P3 or P21 injection. Sensory thresholds and gait analysis were evaluated at P35. Results Intrathecal injection can be reliably performed at all postnatal ages and injectate volume influences segmental spread. Intrathecal morphine produced spinally-mediated analgesia at all ages with lower dose requirements in younger pups. High dose intrathecal morphine did not produce signs of spinal cord toxicity or alter long-term function. Conclusions The therapeutic ratio for intrathecal morphine (toxic dose / antinociceptive dose) was at least 300 at P3, and at least 20 at P21 (latter doses limited by side effects). This data provides relative efficacy and safety data for comparison with other analgesic preparations and contributes supporting evidence for the validity of this preclinical neonatal safety model. PMID:20526189

Validation of a preclinical spinal safety model: effects of intrathecal morphine in the neonatal rat.

PubMed

Westin, B David; Walker, Suellen M; Deumens, Ronald; Grafe, Marjorie; Yaksh, Tony L

2010-07-01

Preclinical studies demonstrate increased neuroapoptosis after general anesthesia in early life. Neuraxial techniques may minimize potential risks, but there has been no systematic evaluation of spinal analgesic safety in developmental models. We aimed to validate a preclinical model for evaluating dose-dependent efficacy, spinal cord toxicity, and long-term function after intrathecal morphine in the neonatal rat. Lumbar intrathecal injections were performed in anesthetized rats aged postnatal day (P) 3, 10, and 21. The relationship between injectate volume and segmental spread was assessed postmortem and by in vivo imaging. To determine the antinociceptive dose, mechanical withdrawal thresholds were measured at baseline and 30 min after intrathecal morphine. To evaluate toxicity, doses up to the maximum tolerated were administered, and spinal cord histopathology, apoptosis, and glial response were evaluated 1 and 7 days after P3 or P21 injection. Sensory thresholds and gait analysis were evaluated at P35. Intrathecal injection can be reliably performed at all postnatal ages and injectate volume influences segmental spread. Intrathecal morphine produced spinally mediated analgesia at all ages with lower dose requirements in younger pups. High-dose intrathecal morphine did not produce signs of spinal cord toxicity or alter long-term function. The therapeutic ratio for intrathecal morphine (toxic dose/antinociceptive dose) was at least 300 at P3 and at least 20 at P21 (latter doses limited by side effects). These data provide relative efficacy and safety for comparison with other analgesic preparations and contribute supporting evidence for the validity of this preclinical neonatal safety model.

Description and Validation of a Dynamical Systems Model of Presynaptic Serotonin Function: Genetic Variation, Brain Activation and Impulsivity

PubMed Central

Stoltenberg, Scott F.; Nag, Parthasarathi

2010-01-01

Despite more than a decade of empirical work on the role of genetic polymorphisms in the serotonin system on behavior, the details across levels of analysis are not well understood. We describe a mathematical model of the genetic control of presynaptic serotonergic function that is based on control theory, implemented using systems of differential equations, and focused on better characterizing pathways from genes to behavior. We present the results of model validation tests that include the comparison of simulation outcomes with empirical data on genetic effects on brain response to affective stimuli and on impulsivity. Patterns of simulated neural firing were consistent with recent findings of additive effects of serotonin transporter and tryptophan hydroxylase-2 polymorphisms on brain activation. In addition, simulated levels of cerebral spinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) were negatively correlated with Barratt Impulsiveness Scale (Version 11) Total scores in college students (r = −.22, p = .002, N = 187), which is consistent with the well-established negative correlation between CSF 5-HIAA and impulsivity. The results of the validation tests suggest that the model captures important aspects of the genetic control of presynaptic serotonergic function and behavior via brain activation. The proposed model can be: (1) extended to include other system components, neurotransmitter systems, behaviors and environmental influences; (2) used to generate testable hypotheses. PMID:20111992

Identification of the sexually dimorphic gastrin-releasing peptide system in the lumbosacral spinal cord that controls male reproductive function in the mouse and Asian house musk shrew (Suncus murinus).

PubMed

Tamura, Kei; Kobayashi, Yasuhisa; Hirooka, Asuka; Takanami, Keiko; Oti, Takumi; Jogahara, Takamichi; Oda, Sen-Ichi; Sakamoto, Tatsuya; Sakamoto, Hirotaka

2017-05-01

Several regions of the brain and spinal cord control male reproductive function. We previously demonstrated that the gastrin-releasing peptide (GRP) system, located in the lumbosacral spinal cord of rats, controls spinal centers to promote penile reflexes during male copulatory behavior. However, little information exists on the male-specific spinal GRP system in animals other than rats. The objective of this study was to examine the functional generality of the spinal GRP system in mammals using the Asian house musk shrew (Suncus murinus; suncus named as the laboratory strain), a specialized placental mammal model. Mice are also used for a representative model of small laboratory animals. We first isolated complementary DNA encoding GRP in suncus. Phylogenetic analysis revealed that suncus preproGRP was clustered to an independent branch. Reverse transcription-PCR showed that GRP and its receptor mRNAs were both expressed in the lumbar spinal cord of suncus and mice. Immunohistochemistry for GRP demonstrated that the sexually dimorphic GRP system and male-specific expression/distribution patterns of GRP in the lumbosacral spinal cord in suncus are similar to those of mice. In suncus, we further found that most GRP-expressing neurons in males also express androgen receptors, suggesting that this male-dominant system in suncus is also androgen-dependent. Taken together, these results indicate that the sexually dimorphic spinal GRP system exists not only in mice but also in suncus, suggesting that this system is a conserved property in mammals. J. Comp. Neurol. 525:1586-1598, 2017. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Spinal cord injury-induced immune deficiency syndrome enhances infection susceptibility dependent on lesion level

PubMed Central

Brommer, Benedikt; Engel, Odilo; Kopp, Marcel A.; Watzlawick, Ralf; Müller, Susanne; Prüss, Harald; Chen, Yuying; DeVivo, Michael J.; Finkenstaedt, Felix W.; Dirnagl, Ulrich; Liebscher, Thomas; Meisel, Andreas

2016-01-01

Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient’s environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P < 0.001) independently from mechanical ventilation and preserved sensory function by multiple regression analysis. We present evidence that spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS (‘immune paralysis’), sufficient to propagate clinically relevant infection in an injury level dependent manner. PMID:26754788

Paralysis recovery in humans and model systems

NASA Technical Reports Server (NTRS)

Edgerton, V. Reggie; Roy, Roland R.

2002-01-01

Considerable evidence now demonstrates that extensive functional and anatomical reorganization following spinal cord injury occurs in centers of the brain that have some input into spinal motor pools. This is very encouraging, given the accumulating evidence that new connections formed across spinal lesions may not be initially functionally useful. The second area of advancement in the field of paralysis recovery is in the development of effective interventions to counter axonal growth inhibition. A third area of significant progress is the development of robotic devices to quantify the performance level of motor tasks following spinal cord injury and to 'teach' the spinal cord to step and stand. Advances are being made with robotic devices for mice, rats and humans.

An Investigation of Jogging Biomechanics using the Full-Body Lumbar Spine Model: Model Development and Validation

PubMed Central

Raabe, Margaret E.; Chaudhari, Ajit M.W.

2016-01-01

The ability of a biomechanical simulation to produce results that can translate to real-life situations is largely dependent on the physiological accuracy of the musculoskeletal model. There are a limited number of freely-available, full-body models that exist in OpenSim, and those that do exist are very limited in terms of trunk musculature and degrees of freedom in the spine. Properly modeling the motion and musculature of the trunk is necessary to most accurately estimate lower extremity and spinal loading. The objective of this study was to develop and validate a more physiologically accurate OpenSim full-body model. By building upon three previously developed OpenSim models, the Full-Body Lumbar Spine (FBLS) model, comprised of 21 segments, 30 degrees-of-freedom, and 324 musculotendon actuators, was developed. The five lumbar vertebrae were modeled as individual bodies, and coupled constraints were implemented to describe the net motion of the spine. The eight major muscle groups of the lumbar spine were modeled (rectus abdominis, external and internal obliques, erector spinae, multifidus, quadratus lumborum, psoas major, and latissimus dorsi), and many of these muscle groups were modeled as multiple fascicles allowing the large muscles to act in multiple directions. The resulting FBLS model's trunk muscle geometry, maximal isometric joint moments, and simulated muscle activations compare well to experimental data. The FBLS model will be made freely available (https://simtk.org/home/fullbodylumbar) for others to perform additional analyses and develop simulations investigating full-body dynamics and contributions of the trunk muscles to dynamic tasks. PMID:26947033

Occupant Responses in a Full-Scale Crash Test of the Sikorsky ACAP Helicopter

NASA Technical Reports Server (NTRS)

Jackson, Karen E.; Fasanella, Edwin L.; Boitnott, Richard L.; McEntire, Joseph; Lewis, Alan

2002-01-01

A full-scale crash test of the Sikorsky Advanced Composite Airframe Program (ACAP) helicopter was performed in 1999 to generate experimental data for correlation with a crash simulation developed using an explicit nonlinear, transient dynamic finite element code. The airframe was the residual flight test hardware from the ACAP program. For the test, the aircraft was outfitted with two crew and two troop seats, and four anthropomorphic test dummies. While the results of the impact test and crash simulation have been documented fairly extensively in the literature, the focus of this paper is to present the detailed occupant response data obtained from the crash test and to correlate the results with injury prediction models. These injury models include the Dynamic Response Index (DRI), the Head Injury Criteria (HIC), the spinal load requirement defined in FAR Part 27.562(c), and a comparison of the duration and magnitude of the occupant vertical acceleration responses with the Eiband whole-body acceleration tolerance curve.

Cervical Spine Injuries: A Whole-Body Musculoskeletal Model for the Analysis of Spinal Loading.

PubMed

Cazzola, Dario; Holsgrove, Timothy P; Preatoni, Ezio; Gill, Harinderjit S; Trewartha, Grant

2017-01-01

Cervical spine trauma from sport or traffic collisions can have devastating consequences for individuals and a high societal cost. The precise mechanisms of such injuries are still unknown as investigation is hampered by the difficulty in experimentally replicating the conditions under which these injuries occur. We harness the benefits of computer simulation to report on the creation and validation of i) a generic musculoskeletal model (MASI) for the analyses of cervical spine loading in healthy subjects, and ii) a population-specific version of the model (Rugby Model), for investigating cervical spine injury mechanisms during rugby activities. The musculoskeletal models were created in OpenSim, and validated against in vivo data of a healthy subject and a rugby player performing neck and upper limb movements. The novel aspects of the Rugby Model comprise i) population-specific inertial properties and muscle parameters representing rugby forward players, and ii) a custom scapula-clavicular joint that allows the application of multiple external loads. We confirm the utility of the developed generic and population-specific models via verification steps and validation of kinematics, joint moments and neuromuscular activations during rugby scrummaging and neck functional movements, which achieve results comparable with in vivo and in vitro data. The Rugby Model was validated and used for the first time to provide insight into anatomical loading and cervical spine injury mechanisms related to rugby, whilst the MASI introduces a new computational tool to allow investigation of spinal injuries arising from other sporting activities, transport, and ergonomic applications. The models used in this study are freely available at simtk.org and allow to integrate in silico analyses with experimental approaches in injury prevention.

Cervical Spine Injuries: A Whole-Body Musculoskeletal Model for the Analysis of Spinal Loading

PubMed Central

Holsgrove, Timothy P.; Preatoni, Ezio; Gill, Harinderjit S.; Trewartha, Grant

2017-01-01

Cervical spine trauma from sport or traffic collisions can have devastating consequences for individuals and a high societal cost. The precise mechanisms of such injuries are still unknown as investigation is hampered by the difficulty in experimentally replicating the conditions under which these injuries occur. We harness the benefits of computer simulation to report on the creation and validation of i) a generic musculoskeletal model (MASI) for the analyses of cervical spine loading in healthy subjects, and ii) a population-specific version of the model (Rugby Model), for investigating cervical spine injury mechanisms during rugby activities. The musculoskeletal models were created in OpenSim, and validated against in vivo data of a healthy subject and a rugby player performing neck and upper limb movements. The novel aspects of the Rugby Model comprise i) population-specific inertial properties and muscle parameters representing rugby forward players, and ii) a custom scapula-clavicular joint that allows the application of multiple external loads. We confirm the utility of the developed generic and population-specific models via verification steps and validation of kinematics, joint moments and neuromuscular activations during rugby scrummaging and neck functional movements, which achieve results comparable with in vivo and in vitro data. The Rugby Model was validated and used for the first time to provide insight into anatomical loading and cervical spine injury mechanisms related to rugby, whilst the MASI introduces a new computational tool to allow investigation of spinal injuries arising from other sporting activities, transport, and ergonomic applications. The models used in this study are freely available at simtk.org and allow to integrate in silico analyses with experimental approaches in injury prevention. PMID:28052130

In vitro and in vivo analysis and characterization of engineered spinal neural implants (Conference Presentation)

NASA Astrophysics Data System (ADS)

Shor, Erez; Shoham, Shy; Levenberg, Shulamit

2016-03-01

Spinal cord injury is a devastating medical condition. Recent developments in pre-clinical and clinical research have started to yield neural implants inducing functional recovery after spinal cord transection injury. However, the functional performance of the transplants was assessed using histology and behavioral experiments which are unable to study cell dynamics and the therapeutic response. Here, we use neurophotonic tools and optogenetic probes to investigate cellular level morphology and activity characteristics of neural implants over time at the cellular level. These methods were used in-vitro and in-vivo, in a mouse spinal cord injury implant model. Following previous attempts to induce recovery after spinal cord injury, we engineered a pre-vascularized implant to obtain better functional performance. To image network activity of a construct implanted in a mouse spinal cord, we transfected the implant to express GCaMP6 calcium activity indicators and implanted these constructs under a spinal cord chamber enabling 2-photon chronic in vivo neural activity imaging. Activity and morphology analysis image processing software was developed to automatically quantify the behavior of the neural and vascular networks. Our experimental results and analyses demonstrate that vascularized and non-vascularized constructs exhibit very different morphologic and activity patterns at the cellular level. This work enables further optimization of neural implants and also provides valuable tools for continuous cellular level monitoring and evaluation of transplants designed for various neurodegenerative disease models.

DTI and pathological changes in a rabbit model of radiation injury to the spinal cord after 125I radioactive seed implantation

PubMed Central

Cao, Xia; Fang, Le; Cui, Chuan-yu; Gao, Shi; Wang, Tian-wei

2018-01-01

Excessive radiation exposure may lead to edema of the spinal cord and deterioration of the nervous system. Magnetic resonance imaging can be used to judge and assess the extent of edema and to evaluate pathological changes and thus may be used for the evaluation of spinal cord injuries caused by radiation therapy. Radioactive 125I seeds to irradiate 90% of the spinal cord tissue at doses of 40–100 Gy (D90) were implanted in rabbits at T10 to induce radiation injury, and we evaluated their safety for use in the spinal cord. Diffusion tensor imaging showed that with increased D90, the apparent diffusion coefficient and fractional anisotropy values were increased. Moreover, pathological damage of neurons and microvessels in the gray matter and white matter was aggravated. At 2 months after implantation, obvious pathological injury was visible in the spinal cords of each group. Magnetic resonance diffusion tensor imaging revealed the radiation injury to the spinal cord, and we quantified the degree of spinal cord injury through apparent diffusion coefficient and fractional anisotropy. PMID:29623940

Biomechanics of compensatory mechanisms in spinal-pelvic complex

NASA Astrophysics Data System (ADS)

Ivanov, D. V.; Hominets, V. V.; Kirillova, I. V.; Kossovich, L. Yu; Kudyashev, A. L.; Teremshonok, A. V.

2018-04-01

3D geometric solid computer model of spinal-pelvic complex was constructed on the basis of computed tomography and full body X-ray in standing position data. The constructed model was used for biomechanical analysis of compensatory mechanisms arising in the spine with anteversion and retroversion of the pelvis. The results of numerical biomechanical 3D modeling are in good agreement with the clinical data.

Predictive Ability of Pender's Health Promotion Model for Physical Activity and Exercise in People with Spinal Cord Injuries: A Hierarchical Regression Analysis

ERIC Educational Resources Information Center

Keegan, John P.; Chan, Fong; Ditchman, Nicole; Chiu, Chung-Yi

2012-01-01

The main objective of this study was to validate Pender's Health Promotion Model (HPM) as a motivational model for exercise/physical activity self-management for people with spinal cord injuries (SCIs). Quantitative descriptive research design using hierarchical regression analysis (HRA) was used. A total of 126 individuals with SCI were recruited…

Autophagy-mediated stress response in motor neurons after hypothermic spinal cord ischemia in rabbits.

PubMed

Fujita, Satoshi; Sakurai, Masahiro; Baba, Hironori; Abe, Koji; Tominaga, Ryuji

2015-11-01

The development of spinal cord injury is believed to be related to the vulnerability of spinal motor neurons to ischemia. However, the mechanisms underlying this vulnerability have not been fully investigated. Previously, we reported that spinal motor neurons are lost likely due to autophagy and that local hypothermia prevents such spinal motor neuron death. Therefore, we investigated the role of autophagy in normothermic and hypothermic spinal cord ischemia using an immunohistochemical analysis of Beclin 1 (BCLN1; B-cell leukemia 2 protein [Bcl-2] interacting protein), Bcl-2, and γ-aminobutyric acid type-A receptor-associated protein (GABARAP), which are considered autophagy-related proteins. We used rabbit normothermic and hypothermic transient spinal cord ischemia models using a balloon catheter. Neurologic function was assessed according to the Johnson score, and the spinal cord was removed at 8 hours and 1, 2, and 7 days after reperfusion, and morphologic changes were examined using hematoxylin and eosin staining. A Western blot analysis and histochemical study of BCLN1, Bcl-2, and GABARAP, and double-labeled fluorescent immunocytochemical studies were performed. There were significant differences in the physiologic function between the normothermic model and hypothermic model after the procedure (P < .05). In the normothermic model, most of the motor neurons were selectively lost at 7 days of reperfusion (P < .001 compared with the sham group), and they were preserved in the hypothermic model (P = .574 compared with the sham group). The Western blot analysis revealed that the sustained expression of the autophagy markers, BCLN1 and GABARAP, was observed (P < .001 compared with the sham group) and was associated with neuronal cell death in normothermic ischemic conditions. In hypothermic ischemic conditions, the autophagy inhibitory protein Bcl-2 was powerfully induced (P < .001 compared with the sham group) and was associated with blunted expression of BCLN1 and GABARAP and neuronal cell survival. The double-label fluorescent immunocytochemical study revealed that immunoreactivitiy for BCLN1, Bcl-2, and GABARAP was induced in the same motor neurons. These data suggest that the prolonged induction of autophagy might be a potential factor responsible for delayed motor neuron death, and the induction of the autophagy inhibitory protein Bcl-2 using hypothermia might limit autophagy and protect against delayed motor neuron death. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Development of less invasive neuromuscular electrical stimulation model for motor therapy in rodents

PubMed Central

Kanchiku, Tsukasa; Kato, Yoshihiko; Suzuki, Hidenori; Imajo, Yasuaki; Yoshida, Yuichiro; Moriya, Atsushi; Taguchi, Toshihiko; Jung, Ranu

2012-01-01

Background Combination therapy is essential for functional repairs of the spinal cord. Rehabilitative therapy can be considered as the key for reorganizing the nervous system after spinal cord regeneration therapy. Functional electrical stimulation has been used as a neuroprosthesis in quadriplegia and can be used for providing rehabilitative therapy to tap the capability for central nervous system reorganization after spinal cord regeneration therapy. Objective To develop a less invasive muscular electrical stimulation model capable of being combined with spinal cord regeneration therapy especially for motor therapy in the acute stage after spinal cord injury. Methods The tibialis anterior and gastrocnemius motor points were identified in intact anesthetized adult female Fischer rats, and stimulation needle electrodes were percutaneously inserted into these points. Threshold currents for visual twitches were obtained upon stimulation using pulses of 75 or 8 kHz for 200 ms. Biphasic pulse widths of 20, 40, 80, 100, 300, and 500 µs per phase were used to determine strength–duration curves. Using these parameters and previously obtained locomotor electromyogram data, stimulations were performed on bilateral joint muscle pairs to produce reciprocal flexion/extension movements of the ankle for 15 minutes while three-dimensional joint kinematics were assessed. Results Rhythmic muscular electrical stimulation with needle electrodes was successfully done, but decreased range of motion (ROM) over time. High-frequency and high-amplitude stimulation was also shown to be effective in alleviating decreases in ROM due to muscle fatigue. Conclusions This model will be useful for investigating the ability of rhythmic muscular electrical stimulation therapy to promote motor recovery, in addition to the efficacy of combining treatments with spinal cord regeneration therapy after spinal cord injuries. PMID:22507026

Standardization of a spinal cord lesion model and neurologic evaluation using mice

PubMed Central

Borges, Paulo Alvim; Cristante, Alexandre Fogaça; de Barros-Filho, Tarcísio Eloy Pessoa; Natalino, Renato Jose Mendonça; dos Santos, Gustavo Bispo; Marcon, Raphael Marcus

2018-01-01

OBJECTIVE: To standardize a spinal cord lesion mouse model. METHODS: Thirty BALB/c mice were divided into five groups: four experimental groups and one control group (sham). The experimental groups were subjected to spinal cord lesion by a weight drop from different heights after laminectomy whereas the sham group only underwent laminectomy. Mice were observed for six weeks, and functional behavior scales were applied. The mice were then euthanized, and histological investigations were performed to confirm and score spinal cord lesion. The findings were evaluated to prove whether the method of administering spinal cord lesion was effective and different among the groups. Additionally, we correlated the results of the functional scales with the results from the histology evaluations to identify which scale is more reliable. RESULTS: One mouse presented autophagia, and six mice died during the experiment. Because four of the mice that died were in Group 5, Group 5 was excluded from the study. All the functional scales assessed proved to be significantly different from each other, and mice presented functional evolution during the experiment. Spinal cord lesion was confirmed by histology, and the results showed a high correlation between the Basso, Beattie, Bresnahan Locomotor Rating Scale and the Basso Mouse Scale. The mouse function scale showed a moderate to high correlation with the histological findings, and the horizontal ladder test had a high correlation with neurologic degeneration but no correlation with the other histological parameters evaluated. CONCLUSION: This spinal cord lesion mouse model proved to be effective and reliable with exception of lesions caused by a 10-g drop from 50 mm, which resulted in unacceptable mortality. The Basso, Beattie, Bresnahan Locomotor Rating Scale and Basso Mouse Scale are the most reliable functional assessments, and but the horizontal ladder test is not recommended. PMID:29561931

Adaptation mechanism of interlimb coordination in human split-belt treadmill walking through learning of foot contact timing: a robotics study

PubMed Central

Fujiki, Soichiro; Aoi, Shinya; Funato, Tetsuro; Tomita, Nozomi; Senda, Kei; Tsuchiya, Kazuo

2015-01-01

Human walking behaviour adaptation strategies have previously been examined using split-belt treadmills, which have two parallel independently controlled belts. In such human split-belt treadmill walking, two types of adaptations have been identified: early and late. Early-type adaptations appear as rapid changes in interlimb and intralimb coordination activities when the belt speeds of the treadmill change between tied (same speed for both belts) and split-belt (different speeds for each belt) configurations. By contrast, late-type adaptations occur after the early-type adaptations as a gradual change and only involve interlimb coordination. Furthermore, interlimb coordination shows after-effects that are related to these adaptations. It has been suggested that these adaptations are governed primarily by the spinal cord and cerebellum, but the underlying mechanism remains unclear. Because various physiological findings suggest that foot contact timing is crucial to adaptive locomotion, this paper reports on the development of a two-layered control model for walking composed of spinal and cerebellar models, and on its use as the focus of our control model. The spinal model generates rhythmic motor commands using an oscillator network based on a central pattern generator and modulates the commands formulated in immediate response to foot contact, while the cerebellar model modifies motor commands through learning based on error information related to differences between the predicted and actual foot contact timings of each leg. We investigated adaptive behaviour and its mechanism by split-belt treadmill walking experiments using both computer simulations and an experimental bipedal robot. Our results showed that the robot exhibited rapid changes in interlimb and intralimb coordination that were similar to the early-type adaptations observed in humans. In addition, despite the lack of direct interlimb coordination control, gradual changes and after-effects in the interlimb coordination appeared in a manner that was similar to the late-type adaptations and after-effects observed in humans. The adaptation results of the robot were then evaluated in comparison with human split-belt treadmill walking, and the adaptation mechanism was clarified from a dynamic viewpoint. PMID:26289658

Adaptation mechanism of interlimb coordination in human split-belt treadmill walking through learning of foot contact timing: a robotics study.

PubMed

Fujiki, Soichiro; Aoi, Shinya; Funato, Tetsuro; Tomita, Nozomi; Senda, Kei; Tsuchiya, Kazuo

2015-09-06

Human walking behaviour adaptation strategies have previously been examined using split-belt treadmills, which have two parallel independently controlled belts. In such human split-belt treadmill walking, two types of adaptations have been identified: early and late. Early-type adaptations appear as rapid changes in interlimb and intralimb coordination activities when the belt speeds of the treadmill change between tied (same speed for both belts) and split-belt (different speeds for each belt) configurations. By contrast, late-type adaptations occur after the early-type adaptations as a gradual change and only involve interlimb coordination. Furthermore, interlimb coordination shows after-effects that are related to these adaptations. It has been suggested that these adaptations are governed primarily by the spinal cord and cerebellum, but the underlying mechanism remains unclear. Because various physiological findings suggest that foot contact timing is crucial to adaptive locomotion, this paper reports on the development of a two-layered control model for walking composed of spinal and cerebellar models, and on its use as the focus of our control model. The spinal model generates rhythmic motor commands using an oscillator network based on a central pattern generator and modulates the commands formulated in immediate response to foot contact, while the cerebellar model modifies motor commands through learning based on error information related to differences between the predicted and actual foot contact timings of each leg. We investigated adaptive behaviour and its mechanism by split-belt treadmill walking experiments using both computer simulations and an experimental bipedal robot. Our results showed that the robot exhibited rapid changes in interlimb and intralimb coordination that were similar to the early-type adaptations observed in humans. In addition, despite the lack of direct interlimb coordination control, gradual changes and after-effects in the interlimb coordination appeared in a manner that was similar to the late-type adaptations and after-effects observed in humans. The adaptation results of the robot were then evaluated in comparison with human split-belt treadmill walking, and the adaptation mechanism was clarified from a dynamic viewpoint. © 2015 The Authors.

Comparison of Motor-Evoked Potentials Versus Somatosensory-Evoked Potentials as Early Indicators of Neural Compromise in Rat Model of Spinal Cord Compression.

PubMed

Morris, Susan H; Howard, Jason J; El-Hawary, Ron

2017-03-15

Randomized controlled study comparing the efficacy of intraoperative somatosensory-evoked potentials (SSEPs) versus transcranial motor-evoked potentials (TcMEPs) as early indicators of neural compromise and predictors of postoperative function in a rat model of spinal cord compression. To compare the relative efficacy of SSEPs and TcMEPs to detect spinal cord compromise and predict postoperative functional deficit after spinal cord compression. There is controversy regarding the efficacy of SSEPs versus TcMEPs to detect intraoperative spinal cord compromise and predict functional outcomes. Previous trials provide some guidance as to the role of each modality in spinal cord monitoring but randomized controlled trials, which are not feasible in humans, are lacking. Twenty-four adult male Wistar rats were evenly divided into three experimental groups and one control group. The experimental groups were determined according to the length of time that 100% TcMEP signal loss was maintained: 0, 5, or 15 minutes. All animals had standardized preoperative functional testing. Spinal cord compromise was initiated utilizing a validated protocol, which involved compression via a balloon catheter introduced into the thoracic sublaminar space. Both SSEPs and TcMEPs were recorded during cord compression for each experimental group. Functional behavioral testing using two validated methods (tilt and modified Tarlov) was repeated 24 hours after termination of spinal cord compression. Post hoc, animals were redistributed into two functional subgroups, noncompromised and compromised, for statistical analysis. TcMEPs consistently detected spinal cord compromise either in advance of or at the same time as SSEPs; however, the delay in SSEP response was not significant for cases when compromised postoperative function resulted. Both SSEP and TcMEP amplitude recovery correlated well with postoperative functional scores. TcMEPs are more sensitive to spinal cord compromise than SSEPs, but the recovery profiles of both SSEP and TcMEP amplitudes are good predictors of postoperative function. 2.

The Cerebellum in Maintenance of a Motor Skill: A Hierarchy of Brain and Spinal Cord Plasticity Underlies H-Reflex Conditioning

ERIC Educational Resources Information Center

Wolpaw, Jonathan R.; Chen, Xiang Yang

2006-01-01

Operant conditioning of the H-reflex, the electrical analog of the spinal stretch reflex, is a simple model of skill acquisition and involves plasticity in the spinal cord. Previous work showed that the cerebellum is essential for down-conditioning the H-reflex. This study asks whether the cerebellum is also essential for maintaining…

Psychometric properties of the International Classification of Functioning, Disability and Health set for spinal cord injury nursing based on Rasch analysis.

PubMed

Li, Kun; Yan, Tiebin; You, Liming; Xie, Sumei; Li, Yun; Tang, Jie; Wang, Yingmin; Gao, Yan

2018-02-01

To examine the psychometric properties of the International Classification of Functioning, Disability and Health (ICF) set for spinal cord injury nursing (ICF-SCIN) using Rasch analysis. A total of 140 spinal cord injury patients were recruited between December 2013 and March 2014 through convenience sampling. Nurses used the components body functions (BF), body structures (BS), and activities and participation (AP) of the ICF-SCIN to rate the patients' functioning. Rasch analysis was performed using RUMM 2030 software. In each component, categories were rescored from 01234 to 01112 because of reversed thresholds. Nine testlets were created to overcome local dependency. Four categories which fit to the Rasch model poorly were deleted. After modification, the components BF, BS, and AP showed good fit to the Rasch model with a Bonferroni-adjusted significant level (χ 2  =   86.29, p = 0.006; χ 2  =   22.44, p = 0.130; χ 2  =   39.92, p = 0.159). The person separation indices (PSIs) for the three components were 0.80, 0.54, and 0.97, respectively. No differential item functioning (DIF) was detected across age, gender, or educational level. The fit properties of the ICF set were satisfactory after modifications. The ICF-SCIN has the potential as a nursing assessment instrument for measuring the functioning of patients with spinal cord injury. Implications for rehabilitation The International Classification of Functioning, Disability and Health (ICF) set for spinal cord injury nursing contains a group of categories which can reflect the functioning of spinal cord injury patients from the perspective of nurses. The components body functions (BF), body structures (BS), and activities and participation (AP) of the ICF set for spinal cord injury achieved the fit to the Rasch model through rescoring, generating testlets, and deleting categories with poor fit. The ICF set for spinal cord injury nursing (ICF-SCIN) has the potential to be used as a clinical nursing assessment tool in measuring the functioning of patients with spinal cord injury.

[RECONSTRUCTION OF LOWER EXTREMITY FUNCTION OF COMPLETE SPINAL CORD INJURY RATS BY FIRST NEURON CONNECTION].

PubMed

Wang, Fangyong; Yuan, Yuan; Li, Jianjun

2015-12-01

To investigate the effects of the first neuron connection for the reconstruction of lower extremity function of complete spinal cord injury rats. Forty adult female Sprague Dawley rats of 300-350 g in weight were selected to prepare the models of L₁ transverse spinal cord injury. After 2 weeks of establishing model, the rats were randomly divided into control group (n = 20) and experimental group (n = 20). In the experimental group, the right hind limb function was reconstructed directly by the first neuron; in the control group, the other treatments were the same to the experimental group except that the distal tibial nerve and the proximal femoral nerve were not sutured. The recovery of motor function of lower extremity was observed by the Basso-Beattie-Bresnahan (BBB) scoring system on bilateral hind limbs at 7, 30, 50, and 70 days after operation. The changes of the spinal cord were observed by HE staining, neurofilament 200 immunohistochemistry staining, and the technique of horseradish peroxidase (HRP) tracing. After establishing models, 6 rats died. The right hind limb had no obvious recovery of the motor function, with the BBB score of 0 in 2 groups; the left hind limb motor function was recovered in different degrees, and there was no significant difference in BBB score between 2 groups (P > 0.05). In the experimental group, HE staining showed that the spinal cord was reconstructed with the sciatic nerve, which was embedded in the spinal cord, and the sciatic nerve membrane was clearly identified, and there was no obvious atrophy in the connecting part of the spinal cord. In the experimental group, the expression of nerve fiber was stained with immunohistochemistry, and the axons of the spinal cord were positively by stained and the peripheral nerve was connected with the spinal cord. HRP labelled synapses were detected by HRP retrograde tracing in the experimental group, while there was no HRP labelled synapse in the control group. Direct reconstruction of the first neurons is sufficient in the regeneration of corresponding neural circuit by the growth of residual axon; but the motor function recovery of the target muscles innervated by peripheral nerve is not observed.

Impact of Therapy on Recovery during Rehabilitation in Patients with Traumatic Spinal Cord Injury

PubMed Central

Fallah, Nader; Santos, Argelio; Vachon, Joëlle; Noonan, Vanessa K.; Cheng, Christiana L.

2017-01-01

Abstract Evidence-based planning of rehabilitation interventions is important to improving cost efficiency while maintaining patient and system outcomes. This article aims to explore the relationship between rehabilitation therapy, functional outcome, bed utilization, and care costs after traumatic spinal cord injury (tSCI). A retrospective review of 262 persons with tSCI admitted to an inpatient rehabilitation facility from 2005–2012 was conducted. Treatment variables and outcome measures included rehabilitation length of stay (LOS), days to rehabilitation (onset), hours and intensity of therapy, and Functional Independence Measure (FIM). Polynomial regression models and generalized additive models were applied to explore the relationship between therapy hours and motor FIM change. Simulation modeling was used to assess the impact of hypothetically increasing therapy intensity. Patients were grouped by injury as: C1–4 American Spinal Injury Association (ASIA) Impairment Scale (AIS) A,B,C; C5–8 AIS A,B,C; T1–S5 AIS A,B,C; and AIS D. The sample was 85% male, mean age 45.9, median LOS 102 days, and mean therapy intensity 5.7 h/week. Motor FIM change was positively associated with total hours of therapy (β = 0.40, p < 0.0001) up to a certain time point, adjusted for age, gender, injury, complications, and rehabilitation onset. Hypothetically increasing therapy intensity by 50% and 100% resulted in average motor FIM efficiency gain ranging between 0.04–0.07 and 0.1–0.17, respectively, across injury groups. The hypothetical changes resulted in reductions in the average LOS and bed utilization rate, translating to cost savings of $20,000 and $50,000 (2011 CAD) for the +50% and +100% scenarios, respectively. The results highlight the importance of monitoring functional change throughout rehabilitation after tSCI and the need for customized therapeutic strategies. PMID:28493787

Ablating spinal NK1-bearing neurons eliminates the development of pain & reduces spinal neuronal hyperexcitability & inflammation from mechanical joint injury in the rat

PubMed Central

Weisshaar, Christine L.; Winkelstein, Beth A.

2014-01-01

The facet joint is a common source of pain especially from mechanical injury. Although chronic pain is associated with altered spinal glial and neuronal responses, the contribution of specific spinal cells to joint pain are not understood. This study used the neurotoxin [Sar9,Met(O2)11]-substance P-saporin (SSP-SAP) to selectively eliminate spinal cells expressing neurokinin-1 receptor (NK1R) in a rat model of painful facet joint injury to determine the role of those spinal neurons in pain from facet injury. Following spinal administration of SSP-SAP or its control (blank-SAP), a cervical facet injury was imposed and behavioral sensitivity assessed. Spinal extracellular recordings were made on day 7 to classify neurons and quantify evoked firing. Spinal glial activation and IL1α expression also were evaluated. SSP-SAP prevented the development of mechanical hyperalgesia that is induced by joint injury and reduced NK1R expression and mechanically-evoked neuronal firing in the dorsal horn. SSP-SAP also prevented a shift toward wide dynamic range neurons that is seen after injury. Spinal astrocytic activation and IL1α expression were reduced to sham levels with SSP-SAP treatment. These results suggest that spinal NK1R-bearing cells are critical in initiating spinal nociception and inflammation associated with a painful mechanical joint injury. Perspective Results demonstrate that cells expressing NK1R in the spinal cord are critical for the development of joint pain and spinal neuroplasticity and inflammation after trauma to the joint. These findings have utility for understanding mechanisms of joint pain and developing potential targets to treat pain. PMID:24389017

Estimation of lumbar spinal loading and trunk muscle forces during asymmetric lifting tasks: application of whole-body musculoskeletal modelling in OpenSim.

PubMed

Kim, Hyun-Kyung; Zhang, Yanxin

2017-04-01

Large spinal compressive force combined with axial torsional shear force during asymmetric lifting tasks is highly associated with lower back injury (LBI). The aim of this study was to estimate lumbar spinal loading and muscle forces during symmetric lifting (SL) and asymmetric lifting (AL) tasks using a whole-body musculoskeletal modelling approach. Thirteen healthy males lifted loads of 7 and 12 kg under two lifting conditions (SL and AL). Kinematic data and ground reaction force data were collected and then processed by a whole-body musculoskeletal model. The results show AL produced a significantly higher peak lateral shear force as well as greater peak force of psoas major, quadratus lumborum, multifidus, iliocostalis lumborum pars lumborum, longissimus thoracis pars lumborum and external oblique than SL. The greater lateral shear forces combined with higher muscle force and asymmetrical muscle contractions may have the biomechanical mechanism responsible for the increased risk of LBI during AL. Practitioner Summary: Estimating lumbar spinal loading and muscle forces during free-dynamic asymmetric lifting tasks with a whole-body musculoskeletal modelling in OpenSim is the core value of this research. The results show that certain muscle groups are fundamentally responsible for asymmetric movement, thereby producing high lumbar spinal loading and muscle forces, which may increase risks of LBI during asymmetric lifting tasks.

Congenital Bone Fractures in Spinal Muscular Atrophy: Functional Role for SMN Protein in Bone Remodeling

PubMed Central

Shanmugarajan, Srinivasan; Swoboda, Kathryn J.; Iannaccone, Susan T.; Ries, William L.; Maria, Bernard L.; Reddy, Sakamuri V.

2009-01-01

Spinal muscular atrophy is the second most common fatal childhood disorder. Core clinical features include muscle weakness caused by degenerating lower motor neurons and a high incidence of bone fractures and hypercalcemia. Fractures further compromise quality of life by progression of joint contractures or additional loss of motor function. Recent observations suggest that bone disease in spinal muscular atrophy may not be attributed entirely to lower motor neuron degeneration. The presence of the spinal muscular atrophy disease-determining survival motor neuron gene (SMN), SMN expression, and differential splicing in bone-resorbing osteoclasts was recently discovered. Its ubiquitous expression and the differential expression of splice variants suggest that SMN has specific roles in bone cell function. SMN protein also interacts with osteoclast stimulatory factor. Mouse models of human spinal muscular atrophy disease suggest a potential role of SMN protein in skeletal development. Dual energy x-ray absorptiometry analysis demonstrated a substantial decrease in total bone area and poorly developed caudal vertebra in the mouse model. These mice also had pelvic bone fractures. Studies delineating SMN signaling mechanisms and gene transcription in a cell-specific manner will provide important molecular insights into the pathogenesis of bone disease in children with spinal muscular atrophy. Moreover, understanding bone remodeling in spinal muscular atrophy may lead to novel therapeutic approaches to enhance skeletal health and quality of life. This article reviews the skeletal complications associated with spinal muscular atrophy and describes a functional role for SMN protein in osteoclast development and bone resorption activity. PMID:17761651

Inhibitory descending rhombencephalic projections in larval sea lamprey.

PubMed

Valle-Maroto, S M; Fernández-López, B; Villar-Cerviño, V; Barreiro-Iglesias, A; Anadón, R; Rodicio, M Celina

2011-10-27

Lampreys are jawless vertebrates, the most basal group of extant vertebrates. This phylogenetic position makes them invaluable models in comparative studies of the vertebrate central nervous system. Lampreys have been used as vertebrate models to study the neuronal circuits underlying locomotion control and axonal regeneration after spinal cord injury. Inhibitory inputs are key elements in the networks controlling locomotor behaviour, but very little is known about the descending inhibitory projections in lampreys. The aim of this study was to investigate the presence of brain-spinal descending inhibitory pathways in larval stages of the sea lamprey Petromyzon marinus by means of tract-tracing with neurobiotin, combined with immunofluorescence triple-labeling methods. Neurobiotin was applied in the rostral spinal cord at the level of the third gill, and inhibitory populations were identified by the use of cocktails of antibodies raised against glycine and GABA. Glycine-immunoreactive (-ir) neurons that project to the spinal cord were observed in three rhombencephalic reticular nuclei: anterior, middle and posterior. Spinal-projecting GABA-ir neurons were observed in the anterior and posterior reticular nuclei. Double glycine-ir/GABA-ir spinal cord-projecting neurons were only observed in the posterior reticular nucleus, and most glycine-ir neurons did not display GABA immunoreactivity. The present results reveal the existence of inhibitory descending projections from brainstem reticular neurons to the spinal cord, which were analyzed in comparative and functional contexts. Further studies should investigate which spinal cord circuits are affected by these descending inhibitory projections. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Mechanical behavior of a novel non-fusion scoliosis correction device.

PubMed

Wessels, M; Hekman, E E G; Verkerke, G J

2013-11-01

We developed an innovative non-fusion correction system (XS LATOR) consisting of two individual implants that are extendable and extremely flexible. One implant, the XS LAT, generates a lateral, bending moment and one implant, the XS TOR, generates a torsion moment. Two 'inverse' implants were developed for generating torsion and lateral bending in a porcine model was tested for force delivery. An in vitro experiment was set up to describe the mechanical behavior of both implants. Narrow and wide ('inverse') versions of the XS TOR and XS LAT were mounted on an apparatus that was able to simulate different spinal geometries. The implants were anchored to three artificial vertebrae with integrated 6D force sensors, after which the vertebrae were rotated and translated towards the demanded position. The reaction forces and moments were recorded in all configurations. The maximal (lateral) bending moment, which occurred at the middle vertebra, was determined and, similarly, torque applied at the center of rotation of the middle vertebra was calculated. As expected, the wide and the small versions of the XS TOR generate a torque that increases during the growth of the system. Similarly, the XS LAT generates a bending moment that slightly increases during the growth of the system. The produced moments approximate the theoretically predicted ones. The contribution to the spinal stiffness ranges between 0.01Nm/° and 0.04Nm/° in bending and between 0.03Nm/° and 0.08Nm/° in torsion. The XS TOR and the XS LAT are able to generate a torque and a bending moment that remain (fairly) constant during spinal growth when a shape change due to the generated moment/torque is achieved. The stiffness of the implants is extremely low, being only a fraction of the stiffness of conventional, spinal fusion constructs. Current fusion systems, such as non-segmental spinal constructs generally, have 11 times higher stiffness in torsion and 6 times higher stiffness in lateral bending. Implantation of the XS LATOR adds 9% stiffness in axial rotation and 17% stiffness in lateral bending (to the original spinal stiffness). By preserving the flexibility of the spine after implantation, fusion of the vertebrae in the instrumented region is likely to be prevented. © 2013 Elsevier Ltd. All rights reserved.

Computed myography: three-dimensional reconstruction of motor functions from surface EMG data

NASA Astrophysics Data System (ADS)

van den Doel, Kees; Ascher, Uri M.; Pai, Dinesh K.

2008-12-01

We describe a methodology called computed myography to qualitatively and quantitatively determine the activation level of individual muscles by voltage measurements from an array of voltage sensors on the skin surface. A finite element model for electrostatics simulation is constructed from morphometric data. For the inverse problem, we utilize a generalized Tikhonov regularization. This imposes smoothness on the reconstructed sources inside the muscles and suppresses sources outside the muscles using a penalty term. Results from experiments with simulated and human data are presented for activation reconstructions of three muscles in the upper arm (biceps brachii, bracialis and triceps). This approach potentially offers a new clinical tool to sensitively assess muscle function in patients suffering from neurological disorders (e.g., spinal cord injury), and could more accurately guide advances in the evaluation of specific rehabilitation training regimens.

In vivo imaging of spinal cord in contusion injury model mice by multi-photon microscopy

NASA Astrophysics Data System (ADS)

Oshima, Y.; Horiuchi, H.; Ogata, T.; Hikita, A.; Miura, H.; Imamura, T.

2014-03-01

Fluorescent imaging technique is a promising method and has been developed for in vivo applications in cellular biology. In particular, nonlinear optical imaging technique, multi-photon microscopy has make it possible to analyze deep portion of tissues in living animals such as axons of spinal code. Traumatic spinal cord injuries (SCIs) are usually caused by contusion damages. Therefore, observation of spinal cord tissue after the contusion injury is necessary for understanding cellular dynamics in response to traumatic SCI and development of the treatment for traumatic SCI. Our goal is elucidation of mechanism for degeneration of axons after contusion injuries by establishing SCI model and chronic observation of injured axons in the living animals. Firstly we generated and observed acute SCI model by contusion injury. By using a multi-photon microscope, axons in dorsal cord were visualized approximately 140 micron in depth from the surface. Immediately after injury, minimal morphological change of spinal cord was observed. At 3 days after injury, spinal cord was swelling and the axons seem to be fragmented. At 7 days after injury, increased degradation of axons could be observed, although the image was blurred due to accumulation of the connective tissue. In the present study, we successfully observed axon degeneration after the contusion SCI in a living animal in vivo. Our final goal is to understand molecular mechanisms and cellular dynamics in response to traumatic SCIs in acute and chronic stage.

An international age- and gender-controlled model for the Spinal Cord Injury Ability Realization Measurement Index (SCI-ARMI).

PubMed

Scivoletto, Giorgio; Glass, Clive; Anderson, Kim D; Galili, Tal; Benjamin, Yoav; Front, Lilach; Aidinoff, Elena; Bluvshtein, Vadim; Itzkovich, Malka; Aito, Sergio; Baroncini, Ilaria; Benito-Penalva, Jesùs; Castellano, Simona; Osman, Aheed; Silva, Pedro; Catz, Amiram

2015-01-01

Background. A quadratic formula of the Spinal Cord Injury Ability Realization Measurement Index (SCI-ARMI) has previously been published. This formula was based on a model of Spinal Cord Independence Measure (SCIM95), the 95th percentile of the SCIM III values, which correspond with the American Spinal Injury Association Motor Scores (AMS) of SCI patients. Objective. To further develop the original formula. Setting. Spinal cord injury centers from 6 countries and the Statistical Laboratory, Tel-Aviv University, Israel. Methods. SCIM95 of 661 SCI patients was modeled, using a quantile regression with or without adjustment for age and gender, to calculate SCI-ARMI values. SCI-ARMI gain during rehabilitation and its correlations were examined. Results. A new quadratic SCIM95 model was created. This resembled the previously published model, which yielded similar SCIM95 values in all the countries, after adjustment for age and gender. Without this adjustment, however, only 86% of the non-Israeli SCIM III observations were lower than those SCIM95 values (P < .0001). Adding the variables age and gender to the new model affected the SCIM95 value significantly (P < .04). Adding country information did not add a significant effect (P > .1). SCI-ARMI gain was positive (38.8 ± 22 points, P < .0001) and correlated weakly with admission age and AMS. Conclusions. The original quadratic SCI-ARMI formula is valid for an international population after adjustment for age and gender. The new formula considers more factors that affect functional ability following SCI. © The Author(s) 2014.

Do Not Resonate with Actions: Sentence Polarity Modulates Cortico-Spinal Excitability during Action-Related Sentence Reading

PubMed Central

Liuzza, Marco Tullio; Candidi, Matteo; Aglioti, Salvatore Maria

2011-01-01

Background Theories of embodied language suggest that the motor system is differentially called into action when processing motor-related versus abstract content words or sentences. It has been recently shown that processing negative polarity action-related sentences modulates neural activity of premotor and motor cortices. Methods and Findings We sought to determine whether reading negative polarity sentences brought about differential modulation of cortico-spinal motor excitability depending on processing hand-action related or abstract sentences. Facilitatory paired-pulses Transcranial Magnetic Stimulation (pp-TMS) was applied to the primary motor representation of the right-hand and the recorded amplitude of induced motor-evoked potentials (MEP) was used to index M1 activity during passive reading of either hand-action related or abstract content sentences presented in both negative and affirmative polarity. Results showed that the cortico-spinal excitability was affected by sentence polarity only in the hand-action related condition. Indeed, in keeping with previous TMS studies, reading positive polarity, hand action-related sentences suppressed cortico-spinal reactivity. This effect was absent when reading hand action-related negative polarity sentences. Moreover, no modulation of cortico-spinal reactivity was associated with either negative or positive polarity abstract sentences. Conclusions Our results indicate that grammatical cues prompting motor negation reduce the cortico-spinal suppression associated with affirmative action sentences reading and thus suggest that motor simulative processes underlying the embodiment may involve even syntactic features of language. PMID:21347305

Inhibitory effects of aspirin-triggered resolvin D1 on spinal nociceptive processing in rat pain models.

PubMed

Meesawatsom, Pongsatorn; Burston, James; Hathway, Gareth; Bennett, Andrew; Chapman, Victoria

2016-09-02

Harnessing the actions of the resolvin pathways has the potential for the treatment of a wide range of conditions associated with overt inflammatory signalling. Aspirin-triggered resolvin D1 (AT-RvD1) has robust analgesic effects in behavioural models of pain; however, the potential underlying spinal neurophysiological mechanisms contributing to these inhibitory effects in vivo are yet to be determined. This study investigated the acute effects of spinal AT-RvD1 on evoked responses of spinal neurones in vivo in a model of acute inflammatory pain and chronic osteoarthritic (OA) pain and the relevance of alterations in spinal gene expression to these neurophysiological effects. Pain behaviour was assessed in rats with established carrageenan-induced inflammatory or monosodium iodoacetate (MIA)-induced OA pain, and changes in spinal gene expression of resolvin receptors and relevant enzymatic pathways were examined. At timepoints of established pain behaviour, responses of deep dorsal horn wide dynamic range (WDR) neurones to transcutaneous electrical stimulation of the hind paw were recorded pre- and post direct spinal administration of AT-RvD1 (15 and 150 ng/50 μl). AT-RvD1 (15 ng/50 μl) significantly inhibited WDR neurone responses to electrical stimuli at C- (29 % inhibition) and Aδ-fibre (27 % inhibition) intensities. Both wind-up (53 %) and post-discharge (46 %) responses of WDR neurones in carrageenan-treated animals were significantly inhibited by AT-RvD1, compared to pre-drug response (p < 0.05). These effects were abolished by spinal pre-administration of a formyl peptide receptor 2 (FPR2/ALX) antagonist, butoxy carbonyl-Phe-Leu-Phe-Leu-Phe (BOC-2) (50 μg/50 μl). AT-RvD1 did not alter evoked WDR neurone responses in non-inflamed or MIA-treated rats. Electrophysiological effects in carrageenan-inflamed rats were accompanied by a significant increase in messenger RNA (mRNA) for chemerin (ChemR23) receptor and 5-lipoxygenase-activating protein (FLAP) and a decrease in 15-lipoxygenase (15-LOX) mRNA in the ipsilateral spinal cord of the carrageenan group, compared to controls. Our data suggest that peripheral inflammation-mediated changes in spinal FLAP expression may contribute to the novel inhibitory effects of spinal AT-RvD1 on WDR neuronal excitability, which are mediated by FPR2/ALX receptors. Inflammatory-driven changes in this pathway may offer novel targets for inflammatory pain treatment.

Central control of interlimb coordination and speed‐dependent gait expression in quadrupeds

PubMed Central

Danner, Simon M.; Wilshin, Simon D.; Shevtsova, Natalia A.

2016-01-01

Key points Quadrupeds express different gaits depending on speed of locomotion.Central pattern generators (one per limb) within the spinal cord generate locomotor oscillations and control limb movements. Neural interactions between these generators define interlimb coordination and gait.We present a computational model of spinal circuits representing four rhythm generators with left–right excitatory and inhibitory commissural and fore–hind inhibitory interactions within the cord.Increasing brainstem drive to all rhythm generators and excitatory commissural interneurons induces an increasing frequency of locomotor oscillations accompanied by speed‐dependent gait changes from walk to trot and to gallop and bound.The model closely reproduces and suggests explanations for multiple experimental data, including speed‐dependent gait transitions in intact mice and changes in gait expression in mutants lacking certain types of commissural interneurons. The model suggests the possible circuit organization in the spinal cord and proposes predictions that can be tested experimentally. Abstract As speed of locomotion is increasing, most quadrupeds, including mice, demonstrate sequential gait transitions from walk to trot and to gallop and bound. The neural mechanisms underlying these transitions are poorly understood. We propose that the speed‐dependent expression of different gaits results from speed‐dependent changes in the interactions between spinal circuits controlling different limbs and interlimb coordination. As a result, the expression of each gait depends on (1) left–right interactions within the spinal cord mediated by different commissural interneurons (CINs), (2) fore–hind interactions on each side of the spinal cord and (3) brainstem drives to rhythm‐generating circuits and CIN pathways. We developed a computational model of spinal circuits consisting of four rhythm generators (RGs) with bilateral left–right interactions mediated by V0 CINs (V0D and V0V sub‐types) providing left–right alternation, and conditional V3 CINs promoting left–right synchronization. Fore and hind RGs mutually inhibited each other. We demonstrate that linearly increasing excitatory drives to the RGs and V3 CINs can produce a progressive increase in the locomotor speed accompanied by sequential changes of gaits from walk to trot and to gallop and bound. The model closely reproduces and suggests explanations for the speed‐dependent gait expression observed in vivo in intact mice and in mutants lacking V0V or all V0 CINs. Specifically, trot is not expressed after removal of V0V CINs, and only bound is expressed after removal of all V0 CINs. The model provides important insights into the organization of spinal circuits and neural control of locomotion. PMID:27633893

A Single Bolus of Docosahexaenoic Acid Promotes Neuroplastic Changes in the Innervation of Spinal Cord Interneurons and Motor Neurons and Improves Functional Recovery after Spinal Cord Injury.

PubMed

Liu, Zhuo-Hao; Yip, Ping K; Adams, Louise; Davies, Meirion; Lee, Jae Won; Michael, Gregory J; Priestley, John V; Michael-Titus, Adina T

2015-09-16

Docosahexaenoic acid (DHA) is an ω-3 polyunsaturated fatty acid that is essential in brain development and has structural and signaling roles. Acute DHA administration is neuroprotective and promotes functional recovery in animal models of adult spinal cord injury (SCI). However, the mechanisms underlying this recovery have not been fully characterized. Here we investigated the effects of an acute intravenous bolus of DHA delivered after SCI and characterized DHA-induced neuroplasticity within the adult injured spinal cord. We found robust sprouting of uninjured corticospinal and serotonergic fibers in a rat cervical hemisection SCI model. A mouse pyramidotomy model was used to confirm that this robust sprouting was not species or injury model specific. Furthermore, we demonstrated that corticospinal fibers sprouting to the denervated side of the cord following pyramidotomy contact V2a interneurons. We also demonstrated increased serotonin fibers and synaptophysin in direct contact with motor neurons. DHA also increased synaptophysin in rat cortical cell cultures. A reduction in phosphatase and tensin homolog (PTEN) has been shown to be involved in axonal regeneration and synaptic plasticity. We showed that DHA significantly upregulates miR-21 and downregulates PTEN in corticospinal neurons. Downregulation of PTEN and upregulation of phosphorylated AKT by DHA were also seen in primary cortical neuron cultures and were accompanied by increased neurite outgrowth. In summary, acute DHA induces anatomical and synaptic plasticity in adult injured spinal cord. This study shows that DHA has therapeutic potential in cervical SCI and provides evidence that DHA could exert its beneficial effects in SCI via enhancement of neuroplasticity. In this study, we show that an acute intravenous injection of docosahexaenoic acid (DHA) 30 min after spinal cord injury induces neuroplasticity. We found robust sprouting of uninjured corticospinal and serotonergic fibers in a rat hemisection spinal cord injury model. A mouse pyramidotomy model was used to confirm that the robust sprouting involved V2a interneurons. We show that DHA significantly upregulates miR-21 and phosphorylated AKT, and downregulates phosphatase and tensin homolog (PTEN), which is involved in suppressing anatomical plasticity, in corticospinal neurons and in primary cortical neuron cultures. We conclude that acute DHA can induce anatomical and synaptic plasticity. This provides direct evidence that DHA could exert its beneficial effects in spinal cord injury via neuroplasticity enhancement. Copyright © 2015 the authors 0270-6474/15/3512734-20$15.00/0.

Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats.

PubMed

Gad, Parag; Choe, Jaehoon; Nandra, Mandheerej Singh; Zhong, Hui; Roy, Roland R; Tai, Yu-Chong; Edgerton, V Reggie

2013-01-21

Stimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has been slow to develop due to the invasive nature of the implantation procedures, the lack of versatility in conventional stimulation technology, and the difficulty of ascertaining specific sites of stimulation that would provide optimal amelioration of the motor deficits. Moreover, the development of tools available to control precise stimulation chronically via biocompatible electrodes has been limited. In this paper, we outline the development of this technology and its use in the spinal rat model, demonstrating the ability to identify and stimulate specific sites of the spinal cord to produce discrete motor behaviors in spinal rats using this array. We have designed a chronically implantable, rapidly switchable, high-density platinum based multi-electrode array that can be used to stimulate at 1-100 Hz and 1-10 V in both monopolar and bipolar configurations to examine the electrophysiological and behavioral effects of spinal cord epidural stimulation in complete spinal cord transected rats. In this paper, we have demonstrated the effectiveness of using high-resolution stimulation parameters in the context of improving motor recovery after a spinal cord injury. We observed that rats whose hindlimbs were paralyzed can stand and step when specific sets of electrodes of the array are stimulated tonically (40 Hz). Distinct patterns of stepping and standing were produced by stimulation of different combinations of electrodes on the array located at specific spinal cord levels and by specific stimulation parameters, i.e., stimulation frequency and intensity, and cathode/anode orientation. The array also was used to assess functional connectivity between the cord dorsum to interneuronal circuits and specific motor pools via evoked potentials induced at 1 Hz stimulation in the absence of any anesthesia. Therefore the high density electrode array allows high spatial resolution and the ability to selectively activate different neural pathways within the lumbosacral region of the spinal cord to facilitate standing and stepping in adult spinal rats and provides the capability to evoke motor potentials and thus a means for assessing connectivity between sensory circuits and specific motor pools and muscles.

Dynamic diffusion tensor imaging of spinal cord contusion: A canine model.

PubMed

Liu, Changbin; Yang, Degang; Li, Jianjun; Li, Dapeng; Yang, Mingliang; Sun, Wei; Meng, Qianru; Zhang, Wenhao; Cai, Chang; Du, Liangjie; Li, Jun; Gao, Feng; Gu, Rui; Feng, Yutong; Dong, Xuechao; Miao, Qi; Yang, Xinghua; Zuo, Zhentao

2018-06-01

This study aimed to explore the dynamic diffusion tensor imaging (DTI) of changes in spinal cord contusion using a canine model of injury involving rostral and caudal levels. In this study, a spinal cord contusion model was established in female dogs using a custom-made weight-drop lesion device. DTI was performed on dogs with injured spinal cords (n=7) using a Siemens 3.0T MRI scanner at pre-contusion and at 3 h, 24 h, 6 weeks and 12 weeks post-injury. The tissue sections were stained for immunohistochemical analysis. Canine models of spinal cord contusion were created successfully using the weight-drop lesion device. The fractional anisotropy (FA) value of lesion epicenter decreased, while the apparent diffusion coefficient (ADC), mean diffusivity (MD), and radial diffusivity (RD) values increased, and the extent of the curve was apparent gradually. The site and time affected the DTI parameters significantly in the whole spinal cord, ADC (site, P < 0.001 and time, P = 0.077, respectively); FA (site, P < 0.001 and time, P = 0.002, respectively). Immunohistological analysis of GFAP and NF revealed the pathologic changes of reactive astrocytes and axons, as well as the cavity and glial scars occurring during chronic SCI. DTI is a sensitive and noninvasive imaging tool useful to assess edema, hemorrhage, cavity formation, structural damage and reconstruction of axon, and myelin in dogs. The DTI parameters after contusion vary. However, the curves of ADC, MD, and RD were nearly similar and the FA curve was distinct. All the DTI parameters were affected by distance and time. © 2018 Wiley Periodicals, Inc.

Crew Exploration Vehicle (CEV) (Orion) Occupant Protection. [Appendices Part 2

NASA Technical Reports Server (NTRS)

Currie-Gregg, Nancy J.; Gernhardt, Michael L.; Lawrence, Charles; Somers, Jeffrey T.

2016-01-01

The purpose of this study was to determine the similarity between the response of the THUMS model and the Hybrid III Anthropometric Test Device (ATD) given existing Wright-Patterson (WP) sled tests. There were four tests selected for this comparison with frontal, spinal, rear, and lateral loading. The THUMS was placed in a sled configuration that replicated the WP configuration and the recorded seat acceleration for each test was applied to model seat. Once the modeling simulations were complete, they were compared to the WP results using two methods. The first was a visual inspection of the sled test videos compared to the THUMS d3plot files. This comparison resulted in an assessment of the overall kinematics of the two results. The other comparison was a comparison of the plotted data recorded for both tests. The metrics selected for comparison were seat acceleration, belt forces, head acceleration and chest acceleration. These metrics were recorded in all WP tests and were outputs of the THUMS model. Once the comparison of the THUMS to the WP tests was complete, the THUMS model output was also examined for possible injuries in these scenarios. These outputs included metrics for injury risk to the head, neck, thorax, lumbar spine and lower extremities. The metrics to evaluate head response were peak head acceleration, HIC15, and HIC36. For the neck, N (sub ij) was calculated. The thorax response was evaluated with peak chest acceleration, the Combined Thoracic Index (CTI), sternal deflection, chest deflection, and chest acceleration- 3 ms clip. The lumbar spine response was evaluated with lumbar spine force. Finally the lower extremity response was evaluated by femur and tibia force. The results of the simulation comparisons indicate the THUMS model had a similar response to the Hybrid III dummy given the same input. The primary difference seen between the two was a more flexible response of the THUMS compared to the Hybrid III. This flexibility was most pronounced in the neck flexion, shoulder deflection and chest deflection. Due to the flexibility of the THUMS, the resulting head and chest accelerations tended to lag the Hybrid III acceleration trace and have a lower peak value. The results of the injury metric comparison identified possible injury trends between simulations. Risk of head injury was highest for the lateral simulations. The risk of chest injury was highest for the rear impact. However, neck injury risk was approximately the same for all simulations. The injury metric value for lumbar spine force was highest for the spinal impact. The leg forces were highest for the rear and lateral impacts. The results of this comparison indicate the THUMS model performs in a similar manner as the Hybrid III ATD. The differences in the responses of model and the ATD are primarily due to the flexibility of the THUMS. This flexibility of the THUMS would be a more human like response. Based on the similarity between the two models, the THUMS should be used in further testing to assess risk of injury to the occupant.

Systemic hypothermia for the treatment of acute cervical spinal cord injury in sports.

PubMed

Dietrich, William Dalton; Cappuccino, Andrew; Cappuccino, Helen

2011-01-01

Spinal cord injury is a devastating condition that affects approximately 12,000 patients each year in the United States. Major causes for spinal cord injury include motor vehicle accidents, sports-related injuries, and direct trauma. Moderate hypothermia has gained attention as a potential therapy due to recent experimental and clinical studies and the use of modest systemic hypothermia (MSH) in high profile case of spinal cord injury in a National Football League (NFL) player. In experimental models of spinal cord injury, moderate hypothermia has been shown to improve functional recovery and reduce overall structural damage. In a recent Phase I clinical trial, systemic hypothermia has been shown to be safe and provide some encouraging results in terms of functional recovery. This review will summarize recent preclinical data, as well as clinical findings that support the continued investigations for the use of hypothermia in severe cervical spinal cord injury.

A ‘tool box’ for deciphering neuronal circuits in the developing chick spinal cord

PubMed Central

Hadas, Yoav; Etlin, Alex; Falk, Haya; Avraham, Oshri; Kobiler, Oren; Panet, Amos; Lev-Tov, Aharon; Klar, Avihu

2014-01-01

The genetic dissection of spinal circuits is an essential new means for understanding the neural basis of mammalian behavior. Molecular targeting of specific neuronal populations, a key instrument in the genetic dissection of neuronal circuits in the mouse model, is a complex and time-demanding process. Here we present a circuit-deciphering ‘tool box’ for fast, reliable and cheap genetic targeting of neuronal circuits in the developing spinal cord of the chick. We demonstrate targeting of motoneurons and spinal interneurons, mapping of axonal trajectories and synaptic targeting in both single and populations of spinal interneurons, and viral vector-mediated labeling of pre-motoneurons. We also demonstrate fluorescent imaging of the activity pattern of defined spinal neurons during rhythmic motor behavior, and assess the role of channel rhodopsin-targeted population of interneurons in rhythmic behavior using specific photoactivation. PMID:25147209

Nonreciprocal mechanisms in up- and downregulation of spinal motoneuron excitability by modulators of KCNQ/Kv7 channels.

PubMed

Lombardo, Joseph; Harrington, Melissa A

2016-11-01

KCNQ/K v 7 channels form a slow noninactivating K + current, also known as the M current. They activate in the subthreshold range of membrane potentials and regulate different aspects of excitability in neurons of the central nervous system. In spinal motoneurons (MNs), KCNQ/K v 7 channels have been identified in the somata, axonal initial segment, and nodes of Ranvier, where they generate a slow, noninactivating, K + current sensitive to both muscarinic receptor-mediated inhibition and KCNQ/K v 7 channel blockers. In this study, we thoroughly reevaluated the function of up- and downregulation of KCNQ/K v 7 channels in mouse immature spinal MNs. Using electrophysiological techniques together with specific pharmacological modulators of the activity of KCNQ/K v 7 channels, we show that enhancement of the activity of these channels decreases the excitability of spinal MNs in mouse neonates. This action on MNs results from a combination of hyperpolarization of the resting membrane potential, a decrease in the input resistance, and depolarization of the voltage threshold. On the other hand, the effect of inhibition of KCNQ/K v 7 channels suggested that these channels play a limited role in regulating basal excitability. Computer simulations confirmed that pharmacological enhancement of KCNQ/K v 7 channel activity decreases excitability and also suggested that the effects of inhibition of KCNQ/K v 7 channels on the excitability of spinal MNs do not depend on a direct effect in these neurons but likely on spinal cord synaptic partners. These results indicate that KCNQ/K v 7 channels have a fundamental role in the modulation of the excitability of spinal MNs acting both in these neurons and in their local presynaptic partners. Copyright © 2016 the American Physiological Society.

Nonreciprocal mechanisms in up- and downregulation of spinal motoneuron excitability by modulators of KCNQ/Kv7 channels

PubMed Central

Lombardo, Joseph

2016-01-01

KCNQ/Kv7 channels form a slow noninactivating K+ current, also known as the M current. They activate in the subthreshold range of membrane potentials and regulate different aspects of excitability in neurons of the central nervous system. In spinal motoneurons (MNs), KCNQ/Kv7 channels have been identified in the somata, axonal initial segment, and nodes of Ranvier, where they generate a slow, noninactivating, K+ current sensitive to both muscarinic receptor-mediated inhibition and KCNQ/Kv7 channel blockers. In this study, we thoroughly reevaluated the function of up- and downregulation of KCNQ/Kv7 channels in mouse immature spinal MNs. Using electrophysiological techniques together with specific pharmacological modulators of the activity of KCNQ/Kv7 channels, we show that enhancement of the activity of these channels decreases the excitability of spinal MNs in mouse neonates. This action on MNs results from a combination of hyperpolarization of the resting membrane potential, a decrease in the input resistance, and depolarization of the voltage threshold. On the other hand, the effect of inhibition of KCNQ/Kv7 channels suggested that these channels play a limited role in regulating basal excitability. Computer simulations confirmed that pharmacological enhancement of KCNQ/Kv7 channel activity decreases excitability and also suggested that the effects of inhibition of KCNQ/Kv7 channels on the excitability of spinal MNs do not depend on a direct effect in these neurons but likely on spinal cord synaptic partners. These results indicate that KCNQ/Kv7 channels have a fundamental role in the modulation of the excitability of spinal MNs acting both in these neurons and in their local presynaptic partners. PMID:27512022

Antibacterial effect of royal jelly for preservation of implant-related spinal infection in rat.

PubMed

Gunaldi, Omur; Daglioglu, Yusuf Kenan; Tugcu, Bekir; Kizilyildirim, Suna; Postalci, Lutfi; Ofluoglu, Ender; Koksal, Fatih

2014-01-01

Implant-related infections are still a significant problem in spinal surgical procedures. Many drugs and methods have been tried to prevent implant-related infections. Our objective in this study was to evaluate whether royal jelly, which was found to hinder the growth of MRSA, has any preventive role in the prognosis of an infection in rats in an implant-related infection model. Rats were divided into 3 groups of eight rats. Group-1 consisted of rats that underwent only a spinal implant, group-2 included those rats that were inoculated bacteria together with a spinal implant and group-3 was administered royal jelly in addition to a spinal implant and infection. The amount of bacteria that grew in vertebral columns and implants was more in Group-2 than in Group-3, which meant that the number of bacteria colonies that grew was more quantitatively. This difference was found to be statistically significant in vertebral columns, but not in implants. Royal jelly could not fully prevent the MRSA infection in this model, but decreased the severity of infection noticeably. More objective and promising results may be obtained if royal jelly can be used at regular intervals in a different model to be designed with respect to implant-related infections.

Intrinsic and Extrinsic Contributions to Seated Balance in the Sagittal and Coronal Planes: Implications for Trunk Control After Spinal Cord Injury.

PubMed

Audu, Musa L; Triolo, Ronald J

2015-08-01

The contributions of intrinsic (passive) and extrinsic (active) properties of the human trunk, in terms of the simultaneous actions about the hip and spinal joints, to the control of sagittal and coronal seated balance were examined. Able-bodied (ABD) and spinal-cord-injured (SCI) volunteers sat on a moving platform which underwent small amplitude perturbations in the anterior-posterior (AP) and medial-lateral (ML) directions while changes to trunk orientation were measured. A linear parametric model that related platform movement to trunk angle was fit to the experimental data by identifying model parameters in the time domain. The results showed that spinal cord injury leads to a systematic reduction in the extrinsic characteristics, while most of the intrinsic characteristics were rarely affected. In both SCI and ABD individuals, passive characteristics alone were not enough to maintain seated balance. Passive stiffness in the ML direction was almost 3 times that in the AP direction, making more extrinsic mechanisms necessary for balance in the latter direction. Proportional and derivative terms of the extrinsic model made the largest contribution to the overall output from the active system, implying that a simple proportional plus derivative (PD) controller structure will suffice for restoring seated balance after spinal cord injury.

Effects of Enhanced Oxygen Delivery by Perfluorocarbons in Spinal Cord Injury

DTIC Science & Technology

2013-10-01

been established, linking post- traumatic ischemia to axonal dysfunction.8 Decreased oxygen level in severe traumatic injuries appears to be implicated...rodent weight drop traumatic spinal cord injury model; ( 2 ) determine if enhanced oxygen delivery in spinal cord injury spares cellular elements, white...shown that ischemia /hypoxia play crucial role in the devastating effects of the secondary injury following SCI which translates into worse neurological

2-Decenoic acid ethyl ester, a derivative of unsaturated medium-chain fatty acids, facilitates functional recovery of locomotor activity after spinal cord injury.

PubMed

Hirakawa, A; Shimizu, K; Fukumitsu, H; Soumiya, H; Iinuma, M; Furukawa, S

2010-12-29

There is increasing evidence that omega-3 polyunsaturated fatty acids (PUFAs) have therapeutic potential in various animal models of neuronal injury. However, very few studies have examined the effect of medium-chain fatty acids (MCFAs) on neuronal injury. So in the present study we synthesized various MCFAs and their derivatives, and found that exposure to trans-2-decenoic acid ethyl ester (DAEE) markedly activated extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in cultured cortical neurons. Therefore, we examined the effect of DAEE treatment on a rat model of spinal cord injury. DAEE (150 μg/kg body weight) administered after hemisection of the spinal cord resulted in improved functional recovery, decreased the lesion size, increased the activation of ERK1/2, and enhanced the expression of bcl-2 and brain-derived neurotrophic factor (BDNF) mRNA in the injury site of the spinal cord. Furthermore, it also increased neuronal survival after spinal cord injury. These results indicate that the possibility that DAEE will become a promising tool for reducing the secondary damage observed following primary physical injury to the spinal cord. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Induction of parkinsonism-related proteins in the spinal motor neurons of transgenic mouse carrying a mutant SOD1 gene.

PubMed

Morimoto, Nobutoshi; Nagai, Makiko; Miyazaki, Kazunori; Ohta, Yasuyuki; Kurata, Tomoko; Takehisa, Yasushi; Ikeda, Yoshio; Matsuura, Tohru; Asanuma, Masato; Abe, Koji

2010-06-01

Amyotrophic lateral sclerosis is a progressive and fatal disease caused by selective death of motor neurons, and a number of these patients carry mutations in the superoxide dismutase 1 (SOD1) gene involved in ameliorating oxidative stress. Recent studies indicate that oxidative stress and disruption of mitochondrial homeostasis is a common mechanism for motor neuron degeneration in amyotrophic lateral sclerosis and the loss of midbrain dopamine neurons in Parkinson's disease. Therefore, the present study investigated the presence and alterations of familial Parkinson's disease-related proteins, PINK1 and DJ-1, in spinal motor neurons of G93ASOD1 transgenic mouse model of amyotrophic lateral sclerosis. Following onset of disease, PINK1 and DJ-1 protein expression increased in the spinal motor neurons. The activated form of p53 also increased and translocated to the nuclei of spinal motor neurons, followed by increased expression of p53-activated gene 608 (PAG608). This is the first report demonstrating that increased expression of PAG608 correlates with activation of phosphorylated p53 in spinal motor neurons of an amyotrophic lateral sclerosis model. These results provide further evidence of the profound correlations between spinal motor neurons of amyotrophic lateral sclerosis and parkinsonism-related proteins.

Spinal Ischemia in Thoracic Aortic Procedures: Impact of Radiculomedullary Artery Distribution.

PubMed

Kari, Fabian A; Wittmann, Karin; Krause, Sonja; Saravi, Babak; Puttfarcken, Luisa; Förster, Katharina; Rylski, Bartosz; Maier, Sven; Göbel, Ulrich; Siepe, Matthias; Czerny, Martin; Beyersdorf, Friedhelm

2017-12-01

The aim of this study was to assess the influence of thoracic anterior radiculomedullary artery (tARMA) distribution on spinal cord perfusion in a thoracic aortic surgical model. Twenty-six pigs (34 ± 3 kg; study group, n = 20; sham group, n = 6) underwent ligation of the left subclavian artery and thoracic segmental arteries. End points were spinal cord perfusion pressure (SCPP), regional spinal cord blood flow (SCBF), and neurologic outcome with an observation time of 3 hours. tARMA distribution patterns tested for an effect on end points included (1) maximum distance between any 2 tARMAs within the treated aortic segment (0 or 1 segment = small-distance group; >1 segment = large-distance group) and (2) distance between the end of the treated aortic segment and the first distal tARMA (at the level of the distal simulated stent-graft end = group 0; gap of 1 or more segments = group ≥1). The number of tARMA ranged from 3 to 13 (mean, 8). In the large-distance group, SCBF dropped from 0.48 ± 0.16 mL/g/min to 0.3 ± 0.08 mL/g/min (p < 0.001). We observed no detectable SCBF drop in the small-distance group: 0.2 ± 0.05 mL/g/min at baseline to 0.23 ± 0.05 mL/g/min immediately after clamping (p = 0.147). SCBF increased from 0.201 ± 0.055 mL/g/min at baseline to 0.443 ± 0.051 mL/g/min at 3 hours postoperatively (p < 0.001) only in the small-distance group. We demonstrate experimental data showing that distribution patterns of tARMAs correlate with the degree of SCBF drop and insufficient reactive parenchymal hyperemia in aortic procedures. Individual ARMA distribution patterns along the treated aortic segment could help us predict the individual risk of spinal ischemia. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

A 3D subject-specific model of the spinal subarachnoid space with anatomically realistic ventral and dorsal spinal cord nerve rootlets.

PubMed

Sass, Lucas R; Khani, Mohammadreza; Natividad, Gabryel Connely; Tubbs, R Shane; Baledent, Olivier; Martin, Bryn A

2017-12-19

The spinal subarachnoid space (SSS) has a complex 3D fluid-filled geometry with multiple levels of anatomic complexity, the most salient features being the spinal cord and dorsal and ventral nerve rootlets. An accurate anthropomorphic representation of these features is needed for development of in vitro and numerical models of cerebrospinal fluid (CSF) dynamics that can be used to inform and optimize CSF-based therapeutics. A subject-specific 3D model of the SSS was constructed based on high-resolution anatomic MRI. An expert operator completed manual segmentation of the CSF space with detailed consideration of the anatomy. 31 pairs of semi-idealized dorsal and ventral nerve rootlets (NR) were added to the model based on anatomic reference to the magnetic resonance (MR) imaging and cadaveric measurements in the literature. Key design criteria for each NR pair included the radicular line, descending angle, number of NR, attachment location along the spinal cord and exit through the dura mater. Model simplification and smoothing was performed to produce a final model with minimum vertices while maintaining minimum error between the original segmentation and final design. Final model geometry and hydrodynamics were characterized in terms of axial distribution of Reynolds number, Womersley number, hydraulic diameter, cross-sectional area and perimeter. The final model had a total of 139,901 vertices with a total CSF volume within the SSS of 97.3 cm 3 . Volume of the dura mater, spinal cord and NR was 123.1, 19.9 and 5.8 cm 3 . Surface area of these features was 318.52, 112.2 and 232.1 cm 2 respectively. Maximum Reynolds number was 174.9 and average Womersley number was 9.6, likely indicating presence of a laminar inertia-dominated oscillatory CSF flow field. This study details an anatomically realistic anthropomorphic 3D model of the SSS based on high-resolution MR imaging of a healthy human adult female. The model is provided for re-use under the Creative Commons Attribution-ShareAlike 4.0 International license (CC BY-SA 4.0) and can be used as a tool for development of in vitro and numerical models of CSF dynamics for design and optimization of intrathecal therapeutics.

Neurite, a Finite Difference Large Scale Parallel Program for the Simulation of Electrical Signal Propagation in Neurites under Mechanical Loading

PubMed Central

García-Grajales, Julián A.; Rucabado, Gabriel; García-Dopico, Antonio; Peña, José-María; Jérusalem, Antoine

2015-01-01

With the growing body of research on traumatic brain injury and spinal cord injury, computational neuroscience has recently focused its modeling efforts on neuronal functional deficits following mechanical loading. However, in most of these efforts, cell damage is generally only characterized by purely mechanistic criteria, functions of quantities such as stress, strain or their corresponding rates. The modeling of functional deficits in neurites as a consequence of macroscopic mechanical insults has been rarely explored. In particular, a quantitative mechanically based model of electrophysiological impairment in neuronal cells, Neurite, has only very recently been proposed. In this paper, we present the implementation details of this model: a finite difference parallel program for simulating electrical signal propagation along neurites under mechanical loading. Following the application of a macroscopic strain at a given strain rate produced by a mechanical insult, Neurite is able to simulate the resulting neuronal electrical signal propagation, and thus the corresponding functional deficits. The simulation of the coupled mechanical and electrophysiological behaviors requires computational expensive calculations that increase in complexity as the network of the simulated cells grows. The solvers implemented in Neurite—explicit and implicit—were therefore parallelized using graphics processing units in order to reduce the burden of the simulation costs of large scale scenarios. Cable Theory and Hodgkin-Huxley models were implemented to account for the electrophysiological passive and active regions of a neurite, respectively, whereas a coupled mechanical model accounting for the neurite mechanical behavior within its surrounding medium was adopted as a link between electrophysiology and mechanics. This paper provides the details of the parallel implementation of Neurite, along with three different application examples: a long myelinated axon, a segmented dendritic tree, and a damaged axon. The capabilities of the program to deal with large scale scenarios, segmented neuronal structures, and functional deficits under mechanical loading are specifically highlighted. PMID:25680098

Effects of orally administered OP-1206 alpha-CD with loxoprofen-Na on walking dysfunction in the rat neuropathic intermittent claudication model.

PubMed

Nakai, Katsuhiko; Takenobu, Yoshifumi; Takimizu, Hideyuki; Akimaru, Shinji; Ito, Hidenori; Maegawa, Hitoshi; Marsala, Martin; Katsube, Nobuo

2003-10-01

An orally active prostaglandin E1 analogue, OP-1206 alpha-CD improves walking dysfunction in the rat spinal stenosis model. Loxoprofen-Na, a non-steroidal anti-inflammatory drug, is used to relieve chronic pain in patients with lumbar spinal canal stenosis. To determine whether the OP-1206 alpha-CD in combination with loxoprofen-Na could induce a greater therapeutical effect on walking dysfunction and spinal cord blood flow (SCBF) than OP-1206 alpha-CD treatment alone after chronic spinal stenosis in the rat. Spinal stenosis was induced by placing two pieces of silicon rubber strips in the lumbar (L4 and L6) epidural space of rats. After surgery, walking function was measured using a treadmill apparatus and SCBF was measured using a laser-Doppler flow meter. Drugs were administered orally twice a day for 11 days from the day 3 post-surgery. OP-1206 alpha-CD elicited a significant improvement of walking dysfunction on days 7 and 14 post-surgery and significantly increased spinal cord blood flow on day 15, whereas walking dysfunction and SCBF of rats treated with loxoprofen-Na alone remained unchanged. Combined treatment of OP-1206 alpha-CD with loxoprofen-Na did not provide additive therapeutical effect. These results suggest that a significant improvement seen after OP-1206 alpha-CD treatment is primarily mediated by improvement of the local spinal cord blood flow. This effect is not ameliorated or potentiated by a combined treatment with loxoprofen-Na.

Geometric Structure of 3D Spinal Curves: Plane Regions and Connecting Zones

PubMed Central

Berthonnaud, E.; Hilmi, R.; Dimnet, J.

2012-01-01

This paper presents a new study of the geometric structure of 3D spinal curves. The spine is considered as an heterogeneous beam, compound of vertebrae and intervertebral discs. The spine is modeled as a deformable wire along which vertebrae are beads rotating about the wire. 3D spinal curves are compound of plane regions connected together by zones of transition. The 3D spinal curve is uniquely flexed along the plane regions. The angular offsets between adjacent regions are concentrated at level of the middle zones of transition, so illustrating the heterogeneity of the spinal geometric structure. The plane regions along the 3D spinal curve must satisfy two criteria: (i) a criterion of minimum distance between the curve and the regional plane and (ii) a criterion controlling that the curve is continuously plane at the level of the region. The geometric structure of each 3D spinal curve is characterized by the sizes and orientations of regional planes, by the parameters representing flexed regions and by the sizes and functions of zones of transition. Spinal curves of asymptomatic subjects show three plane regions corresponding to spinal curvatures: lumbar, thoracic and cervical curvatures. In some scoliotic spines, four plane regions may be detected. PMID:25031873

Spinal cord stress injury assessment (SCOSIA): clinical applications of mechanical modeling of the spinal cord and brainstem

NASA Astrophysics Data System (ADS)

Wong, Kenneth H.; Choi, Jae; Wilson, William; Berry, Joel; Henderson, Fraser C., Sr.

2009-02-01

Abnormal stretch and strain is a major cause of injury to the spinal cord and brainstem. Such forces can develop from age-related degeneration, congenital malformations, occupational exposure, or trauma such as sporting accidents, whiplash and blast injury. While current imaging technologies provide excellent morphology and anatomy of the spinal cord, there is no validated diagnostic tool to assess mechanical stresses exerted upon the spinal cord and brainstem. Furthermore, there is no current means to correlate these stress patterns with known spinal cord injuries and other clinical metrics such as neurological impairment. We have therefore developed the spinal cord stress injury assessment (SCOSIA) system, which uses imaging and finite element analysis to predict stretch injury. This system was tested on a small cohort of neurosurgery patients. Initial results show that the calculated stress values decreased following surgery, and that this decrease was accompanied by a significant decrease in neurological symptoms. Regression analysis identified modest correlations between stress values and clinical metrics. The strongest correlations were seen with the Brainstem Disability Index (BDI) and the Karnofsky Performance Score (KPS), whereas the weakest correlations were seen with the American Spinal Injury Association (ASIA) scale. SCOSIA therefore shows encouraging initial results and may have wide applicability to trauma and degenerative disease involving the spinal cord and brainstem.

Analytical and experimental investigations of human spine flexure.

NASA Technical Reports Server (NTRS)

Moffatt, C. A.; Advani, S. H.; Lin, C.-J.

1971-01-01

The authors report on experiments to measure the resistance of fresh human spines to flexion in the upper lumbar and lower thoracic regions and evaluate results by using a combination of strength of materials theory and effects of shear and comparing with data reported by other authors. The test results indicate that the thoraco-lumbar spine behaves approximately as a linear elastic beam, without relaxation effects. The authors formulate a simple continuum dynamic model of the spine simulating aircraft ejection and solve the resulting boundary value problem to illustrate the importance of the flexural mode. A constant cross-section, the selected model is a sinusoidally curved elastic beam with an end mass subjected to a Heaviside axial acceleration at the other end. The paper presents transient response results for the spinal model axial and bending displacements and axial force.-

Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy

PubMed Central

Mentis, George Z.; Blivis, Dvir; Liu, Wenfang; Drobac, Estelle; Crowder, Melissa E.; Kong, Lingling; Alvarez, Francisco J.; Sumner, Charlotte J.; O'Donovan, Michael J.

2011-01-01

SUMMARY To define alterations of neuronal connectivity that occur during motor neuron degeneration, we characterized the function and structure of spinal circuitry in spinal muscular atrophy (SMA) model mice. SMA motor neurons show reduced proprioceptive reflexes that correlate with decreased number and function of synapses on motor neuron somata and proximal dendrites. These abnormalities occur at an early stage of disease in motor neurons innervating proximal hindlimb muscles and medial motor neurons innervating axial muscles, but only at end-stage disease in motor neurons innervating distal hindlimb muscles. Motor neuron loss follows afferent synapse loss with the same temporal and topographical pattern. Trichostatin A, which improves motor behavior and survival of SMA mice, partially restores spinal reflexes illustrating the reversibility of these synaptic defects. De-afferentation of motor neurons is an early event in SMA and may be a primary cause of motor dysfunction that is amenable to therapeutic intervention. PMID:21315257

Vestibulo-ocular reflex of the squirrel monkey during eccentric rotation with centripetal acceleration along the naso-occipital axis

NASA Technical Reports Server (NTRS)

Merfeld, D. M.; Paloski, W. H. (Principal Investigator)

1996-01-01

The vestibulo-ocular reflexes (VOR) are determined not only by angular acceleration, but also by the presence of gravity and linear acceleration. This phenomenon was studied by measuring three-dimensional nystagmic eye movements, with implanted search coils, in four male squirrel monkeys. Monkeys were rotated in the dark at 200 degrees/s, centrally or 79 cm off-axis, with the axis of rotation always aligned with gravity and the spinal axis of the upright monkeys. The monkey's position relative to the centripetal acceleration (facing center or back to center) had a dramatic influence on the VOR. These studies show that a torsional response was always elicited that acted to shift the axis of eye rotation toward alignment with gravito-inertial force. On the other hand, a slow phase downward vertical response usually existed, which shifted the axis of eye rotation away from the gravito-inertial force. These findings were consistent across all monkeys. In another set of tests, the same monkeys were rapidly tilted about their interaural (pitch) axis. Tilt orientations of 45 degrees and 90 degrees were maintained for 1 min. Other than a compensatory angular VOR during the rotation, no consistent eye velocity response was ever observed during or following the tilt. The absence of any response following tilt proves that the observed torsional and vertical responses were not a positional nystagmus. Model simulations qualitatively predict all components of these eccentric rotation and tilt responses. These simulations support the conclusion that the VOR during eccentric rotation may consist of two components: a linear VOR and a rotational VOR. The model predicts a slow phase downward, vertical, linear VOR during eccentric rotation even though there was never a change in the force aligned with monkey's spinal (Z) axis. The model also predicts the torsional components of the response that shift the rotation axis of the angular VOR toward alignment with gravito-inertial force.

Vestibulo-ocular reflex of the squirrel monkey during eccentric rotation with centripetal acceleration along the naso-occipital axis.

PubMed

Merfeld, D M

1996-01-01

The vestibulo-ocular reflexes (VOR) are determined not only by angular acceleration, but also by the presence of gravity and linear acceleration. This phenomenon was studied by measuring three-dimensional nystagmic eye movements, with implanted search coils, in four male squirrel monkeys. Monkeys were rotated in the dark at 200 degrees/s, centrally or 79 cm off-axis, with the axis of rotation always aligned with gravity and the spinal axis of the upright monkeys. The monkey's position relative to the centripetal acceleration (facing center or back to center) had a dramatic influence on the VOR. These studies show that a torsional response was always elicited that acted to shift the axis of eye rotation toward alignment with gravito-inertial force. On the other hand, a slow phase downward vertical response usually existed, which shifted the axis of eye rotation away from the gravito-inertial force. These findings were consistent across all monkeys. In another set of tests, the same monkeys were rapidly tilted about their interaural (pitch) axis. Tilt orientations of 45 degrees and 90 degrees were maintained for 1 min. Other than a compensatory angular VOR during the rotation, no consistent eye velocity response was ever observed during or following the tilt. The absence of any response following tilt proves that the observed torsional and vertical responses were not a positional nystagmus. Model simulations qualitatively predict all components of these eccentric rotation and tilt responses. These simulations support the conclusion that the VOR during eccentric rotation may consist of two components: a linear VOR and a rotational VOR. The model predicts a slow phase downward, vertical, linear VOR during eccentric rotation even though there was never a change in the force aligned with monkey's spinal (Z) axis. The model also predicts the torsional components of the response that shift the rotation axis of the angular VOR toward alignment with gravito-inertial force.

Established Stem Cell Model of Spinal Muscular Atrophy Is Applicable in the Evaluation of the Efficacy of Thyrotropin-Releasing Hormone Analog

PubMed Central

Ohuchi, Kazuki; Kato, Zenichiro; Seki, Junko; Kawase, Chizuru; Tamai, Yuya; Ono, Yoko; Nagahara, Yuki; Noda, Yasuhiro; Kameyama, Tsubasa; Ando, Shiori; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Hara, Hideaki; Kaneko, Hideo

2016-01-01

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by the degeneration of spinal motor neurons. This disease is mainly caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Currently, no effective treatment is available, and only symptomatic treatment can be provided. Our purpose in the present study was to establish a human SMA-derived induced pluripotent stem cell (SMA-iPSC) disease model and assay a therapeutic drug in preparation for the development of a novel treatment of SMA. We generated iPSCs from the skin fibroblasts of a patient with SMA and confirmed that they were pluripotent and undifferentiated. The neural differentiation of SMA-iPSCs shortened the dendrite and axon length and increased the apoptosis of the spinal motor neurons. In addition, we found activated astrocytes in differentiated SMA-iPSCs. Using this model, we confirmed that treatment with the thyrotropin-releasing hormone (TRH) analog, 5-oxo-l-prolyl-l-histidyl-l-prolinamide, which had marginal effects in clinical trials, increases the SMN protein level. This increase was mediated through the transcriptional activation of the SMN2 gene and inhibition of glycogen synthase kinase-3β activity. Finally, the TRH analog treatment resulted in dendrite and axon development of spinal motor neurons in differentiated SMA-iPSCs. These results suggest that this human in vitro disease model stimulates SMA pathology and reveal the potential efficacy of TRH analog treatment for SMA. Therefore, we can screen novel therapeutic drugs such as TRH for SMA easily and effectively using the human SMA-iPSC model. Significance Platelet-derived growth factor (PDGF) has recently been reported to produce the greatest increase in survival motor neuron protein levels by inhibiting glycogen synthase kinase (GSK)-3β; however, motor neurons lack PDGF receptors. A human in vitro spinal muscular atrophy-derived induced pluripotent stem cell model was established, which showed that the thyrotropin releasing hormone (TRH) analog promoted transcriptional activation of the SMN2 gene and inhibition of GSK-3β activity, resulting in the increase and stabilization of the SMN protein and axon elongation of spinal motor neurons. These results reveal the potential efficacy of TRH analog treatment for SMA. PMID:26683872

Established Stem Cell Model of Spinal Muscular Atrophy Is Applicable in the Evaluation of the Efficacy of Thyrotropin-Releasing Hormone Analog.

PubMed

Ohuchi, Kazuki; Funato, Michinori; Kato, Zenichiro; Seki, Junko; Kawase, Chizuru; Tamai, Yuya; Ono, Yoko; Nagahara, Yuki; Noda, Yasuhiro; Kameyama, Tsubasa; Ando, Shiori; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Hara, Hideaki; Kaneko, Hideo

2016-02-01

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by the degeneration of spinal motor neurons. This disease is mainly caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Currently, no effective treatment is available, and only symptomatic treatment can be provided. Our purpose in the present study was to establish a human SMA-derived induced pluripotent stem cell (SMA-iPSC) disease model and assay a therapeutic drug in preparation for the development of a novel treatment of SMA. We generated iPSCs from the skin fibroblasts of a patient with SMA and confirmed that they were pluripotent and undifferentiated. The neural differentiation of SMA-iPSCs shortened the dendrite and axon length and increased the apoptosis of the spinal motor neurons. In addition, we found activated astrocytes in differentiated SMA-iPSCs. Using this model, we confirmed that treatment with the thyrotropin-releasing hormone (TRH) analog, 5-oxo-l-prolyl-l-histidyl-l-prolinamide, which had marginal effects in clinical trials, increases the SMN protein level. This increase was mediated through the transcriptional activation of the SMN2 gene and inhibition of glycogen synthase kinase-3β activity. Finally, the TRH analog treatment resulted in dendrite and axon development of spinal motor neurons in differentiated SMA-iPSCs. These results suggest that this human in vitro disease model stimulates SMA pathology and reveal the potential efficacy of TRH analog treatment for SMA. Therefore, we can screen novel therapeutic drugs such as TRH for SMA easily and effectively using the human SMA-iPSC model. Significance: Platelet-derived growth factor (PDGF) has recently been reported to produce the greatest increase in survival motor neuron protein levels by inhibiting glycogen synthase kinase (GSK)-3β; however, motor neurons lack PDGF receptors. A human in vitro spinal muscular atrophy-derived induced pluripotent stem cell model was established, which showed that the thyrotropin releasing hormone (TRH) analog promoted transcriptional activation of the SMN2 gene and inhibition of GSK-3β activity, resulting in the increase and stabilization of the SMN protein and axon elongation of spinal motor neurons. These results reveal the potential efficacy of TRH analog treatment for SMA. ©AlphaMed Press.

[Effect of electroacupuncture of different acupoints on the excitability of detrusor muscle and the expression of BDNF and TrkB in the spinal cord of rats with urinary retention due to spinal cord injury].

PubMed

Wang, Jun-hua; Chen, Bang-guo; Yin, Jing; Wang, Gang; Zou, Wei-Geng; Luo, Xiao-juan

2009-12-01

To observe the effect of electroacupuncture (EA) of different acupoints on the expression of brain-derived neurotrophic factor (BDNF) and tropomyosine receptor kinase B (TrkB) in the spinal cord and the excitability of detrusor muscle of the uninary bladder in rats with urinary retention owing to spinal cord injury (SCI). A total of 100 female SD rats were randomly divided into normal, sham-operation (sham), model, EA-Guanyuan (CV 4), and EA-Shuidao (ST 28) groups, with 20 cases in each. SCI induced urinary retention model was established by using weight dropping method. EA (1 mA, 2 Hz/15 Hz) was applied to "Guanyuan" (CV 4) and "Shuidao" (ST 28) respectively for 20 min, once a day for 10 days. The excitability (tone, contraction frequency) of the detrusor muscle of the bladder was detected in vitro by using electrophysiological method, and the expression of BDNF and TrkB in spinal cord was determined by immunohistochemistry staining. In comparison with normal control and sham groups, the tension and the contraction frequency of detrusor muscle in model group lowered significantly (P<0.05), while compared with model group, both the tension and contraction frequency of detrusor muscle increased pronouncedly in EA-CV 4 and EA-ST 28 groups (P<0.05), and the effect of EA-CV 4 was apparently superior to that of EA-ST 28 (P<0.05). In comparison with normal and sham groups, the BDNF and TrkB immunoreaction positive cells in the spinal cord were significantly more in model group (P<0.05). Compared with model group, those of EA-CV 4 and EA-ST 28 groups were obviously further increased (P<0.05), and the effect of EA-CV 4 group was markedly superior to that of EA-ST 28 group (P<0.05). EA of CV 4 and ST 28 can raise the excitability of the smooth muscle of the uninary bladder in rats with SCI-induced urinary retention, which may be related to its effects in upregulating the expression of BDNF and TrkB in the spinal cord. The effects of EA of CV 4 were evidently superior to those of EA of ST 28.

Biotribological evaluation of artificial disc arthroplasty devices: influence of loading and kinematic patterns during in vitro wear simulation.

PubMed

Grupp, Thomas M; Yue, James J; Garcia, Rolando; Basson, Janet; Schwiesau, Jens; Fritz, Bernhard; Blömer, Wilhelm

2009-01-01

Wear simulation is an essential pre-clinical method to predict the mid- and long-term clinical wear behavior of newly introduced devices for total disc arthroplasty. The main requirement of a suitable method for spinal wear simulation has to be the ability to distinguish between design concepts and allow for a direct comparison of predicate devices. The objective of our study was to investigate the influence of loading and kinematic patterns based on two different protocols for spinal wear simulation (ISO/FDIS 18192-1 (2006) and ASTM F2423-05). In vitro wear simulation was performed with six activ L lumbar artificial disc devices (Aesculap Tuttlingen, Germany). The applied kinematic pattern of movement was multidirectional for ISO (elliptic track) and unidirectional with a curvilinear shape for ASTM. Testing was done for 10 million cycles in the ISO loading mode and afterwards with the same specimens for 5 million cycles according to the ASTM protocol with a customized six-station servohydraulic spinal wear simulator (EndoLab Thansau, Germany). Gravimetrical and geometrical wear assessment, a slide track analysis correlated to an optical surface characterization, and an estimation of particle size and morphology were performed. The gravimetric wear rate for the first 10 million cycles was ISO(initial) = 2.7 +/- 0.3 mg/million cycles. During the ASTM test period (10-15 million cycles) a gravimetric wear rate of 0.14 +/- 0.06 mg/million cycles was estimated. The wear rates between the ISO and ASTM driven simulations differ substantially (approximately 20-fold) and statistical analysis demonstrates a significant difference (p < 0.001) between the test groups. The main explanation of divergency between ISO and ASTM driven wear simulations is the multidirectional pattern of movement described in the ISO document resulting in a cross-shear stress on the polyethylene material. Due to previous retrieval observations, it seems to be very unlikely that a lumbar artificial disc is loaded with a linear wear path.Testing according to ASTM F2423-05 with pure unidirectional motion does not reflect the kinematics of TDA patients' daily activities. Based on our findings it seems to be more reliable to predict the clinical wear behavior of an artificial disc replacement using the ISO/FDIS 18192-1 method.

Biotribological evaluation of artificial disc arthroplasty devices: influence of loading and kinematic patterns during in vitro wear simulation

PubMed Central

Yue, James J.; Garcia, Rolando; Basson, Janet; Schwiesau, Jens; Fritz, Bernhard; Blömer, Wilhelm

2008-01-01

Wear simulation is an essential pre-clinical method to predict the mid- and long-term clinical wear behavior of newly introduced devices for total disc arthroplasty. The main requirement of a suitable method for spinal wear simulation has to be the ability to distinguish between design concepts and allow for a direct comparison of predicate devices. The objective of our study was to investigate the influence of loading and kinematic patterns based on two different protocols for spinal wear simulation (ISO/FDIS 18192-1 (2006) and ASTM F2423-05). In vitro wear simulation was performed with six activ® L lumbar artificial disc devices (Aesculap Tuttlingen, Germany). The applied kinematic pattern of movement was multidirectional for ISO (elliptic track) and unidirectional with a curvilinear shape for ASTM. Testing was done for 10 million cycles in the ISO loading mode and afterwards with the same specimens for 5 million cycles according to the ASTM protocol with a customized six-station servohydraulic spinal wear simulator (EndoLab Thansau, Germany). Gravimetrical and geometrical wear assessment, a slide track analysis correlated to an optical surface characterization, and an estimation of particle size and morphology were performed. The gravimetric wear rate for the first 10 million cycles was ISOinitial = 2.7 ± 0.3 mg/million cycles. During the ASTM test period (10–15 million cycles) a gravimetric wear rate of 0.14 ± 0.06 mg/million cycles was estimated. The wear rates between the ISO and ASTM driven simulations differ substantially (approximately 20-fold) and statistical analysis demonstrates a significant difference (p < 0.001) between the test groups. The main explanation of divergency between ISO and ASTM driven wear simulations is the multidirectional pattern of movement described in the ISO document resulting in a cross-shear stress on the polyethylene material. Due to previous retrieval observations, it seems to be very unlikely that a lumbar artificial disc is loaded with a linear wear path.Testing according to ASTM F2423-05 with pure unidirectional motion does not reflect the kinematics of TDA patients‘ daily activities. Based on our findings it seems to be more reliable to predict the clinical wear behavior of an artificial disc replacement using the ISO/FDIS 18192-1 method. PMID:19050942

Nonuniform Moving Boundary Method for Computational Fluid Dynamics Simulation of Intrathecal Cerebrospinal Flow Distribution in a Cynomolgus Monkey.

PubMed

Khani, Mohammadreza; Xing, Tao; Gibbs, Christina; Oshinski, John N; Stewart, Gregory R; Zeller, Jillynne R; Martin, Bryn A

2017-08-01

A detailed quantification and understanding of cerebrospinal fluid (CSF) dynamics may improve detection and treatment of central nervous system (CNS) diseases and help optimize CSF system-based delivery of CNS therapeutics. This study presents a computational fluid dynamics (CFD) model that utilizes a nonuniform moving boundary approach to accurately reproduce the nonuniform distribution of CSF flow along the spinal subarachnoid space (SAS) of a single cynomolgus monkey. A magnetic resonance imaging (MRI) protocol was developed and applied to quantify subject-specific CSF space geometry and flow and define the CFD domain and boundary conditions. An algorithm was implemented to reproduce the axial distribution of unsteady CSF flow by nonuniform deformation of the dura surface. Results showed that maximum difference between the MRI measurements and CFD simulation of CSF flow rates was <3.6%. CSF flow along the entire spine was laminar with a peak Reynolds number of ∼150 and average Womersley number of ∼5.4. Maximum CSF flow rate was present at the C4-C5 vertebral level. Deformation of the dura ranged up to a maximum of 134 μm. Geometric analysis indicated that total spinal CSF space volume was ∼8.7 ml. Average hydraulic diameter, wetted perimeter, and SAS area were 2.9 mm, 37.3 mm and 27.24 mm2, respectively. CSF pulse wave velocity (PWV) along the spine was quantified to be 1.2 m/s.

An investigation of jogging biomechanics using the full-body lumbar spine model: Model development and validation.

PubMed

Raabe, Margaret E; Chaudhari, Ajit M W

2016-05-03

The ability of a biomechanical simulation to produce results that can translate to real-life situations is largely dependent on the physiological accuracy of the musculoskeletal model. There are a limited number of freely-available, full-body models that exist in OpenSim, and those that do exist are very limited in terms of trunk musculature and degrees of freedom in the spine. Properly modeling the motion and musculature of the trunk is necessary to most accurately estimate lower extremity and spinal loading. The objective of this study was to develop and validate a more physiologically accurate OpenSim full-body model. By building upon three previously developed OpenSim models, the full-body lumbar spine (FBLS) model, comprised of 21 segments, 30 degrees-of-freedom, and 324 musculotendon actuators, was developed. The five lumbar vertebrae were modeled as individual bodies, and coupled constraints were implemented to describe the net motion of the spine. The eight major muscle groups of the lumbar spine were modeled (rectus abdominis, external and internal obliques, erector spinae, multifidus, quadratus lumborum, psoas major, and latissimus dorsi), and many of these muscle groups were modeled as multiple fascicles allowing the large muscles to act in multiple directions. The resulting FBLS model׳s trunk muscle geometry, maximal isometric joint moments, and simulated muscle activations compare well to experimental data. The FBLS model will be made freely available (https://simtk.org/home/fullbodylumbar) for others to perform additional analyses and develop simulations investigating full-body dynamics and contributions of the trunk muscles to dynamic tasks. Copyright © 2016 Elsevier Ltd. All rights reserved.

Establishment of a New Zealand rabbit model of spinal tuberculosis.

PubMed

Geng, Guangqi; Wang, Qian; Shi, Jiandang; Yan, Junfa; Niu, Ningkui; Wang, Zili

2015-04-01

This was an experimental study. To investigate and evaluate the experimental method of establishing a New Zealand rabbit model of spinal tuberculosis. Establishing animal models of tuberculosis is critical to the experimental and clinical study of tuberculosis, especially spinal tuberculosis. However, the rapid spread of Mycobacterium tuberculosis and subsequent high mortality thwarted their effort. Since then, no animal models have been established of spinal tuberculosis. Forty-two New Zealand rabbits were randomly divided into experimental (n=20), control (n=20), and blank groups (n=2). Experimental animals were sensitized by complete Freund's adjuvant. A hole drilled under the upper endplate of the L4 vertebral body was filled with a gelfoam sponge infused with 0.1 mL H37Rv standard M. tuberculosis suspension (in controls, culture medium, and saline). Blank animals received no treatment. Survival 8 weeks after surgery was 89.5%, 94.7%, and 100% in experimental, control, and blank groups, respectively. The model was successfully established in all surviving experimental rabbits. In experimental animals, vertebral body destruction at 4 weeks was 50% by x-ray; 83.3% by computed tomography reconstruction and magnetic resonance imaging; at 8 weeks, 58.8% by x-ray and 100% by computed tomograph reconstruction and magnetic resonance imaging. At 8 weeks, experimental animals developed vertebral destruction, granulation, and necrosis and 17.6% had psoas abscess. Histopathology revealed numerous lymphocytes and epithelioid cells, trabecular bone fracture, and coagulative necrosis in the vertebrae of experimental animals; bacterium culture was 52.9% positive. Control and blank animals showed no such changes. A New Zealand rabbit of spinal tuberculosis model can be successfully established by drilling a hole in the upper endplate of the vertebral body, filling with gelfoam sponge infused with H37Rv standard M. tuberculosis suspension after sensitization by complete Freund's adjuvant.

Evaluating Snyder's Hope Theory as a Motivational Model of Participation and Life Satisfaction for Individuals with Spinal Cord Injury: A Path Analysis

ERIC Educational Resources Information Center

Chan, Jacob Yui Chung; Chan, Fong; Ditchman, Nicole; Phillips, Brian; Chou, Chih-Chin

2013-01-01

Objective: To evaluate Snyder's (2002) hope theory as a motivational model of community participation and life satisfaction. Setting: Manitoba chapter of the Canadian Paraplegic Association. Participants: One-hundred and sixteen participants with spinal cord injuries who were members of the Manitoba chapter of the Canadian Paraplegic Association.…

Development of an Animal Model of Thoracolumbar Burst Fracture-Induced Acute Spinal Cord Injury

DTIC Science & Technology

2016-07-01

Final PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for...MONITOR’S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 12...subjected to spinal cord impact with a custom-made controlled spinal cord impactor and balloon compression. Neurological function was assessed for

Concepts on the pathogenesis of adolescent idiopathic scoliosis. Bone growth and mass, vertebral column, spinal cord, brain, skull, extra-spinal left-right skeletal length asymmetries, disproportions and molecular pathogenesis.

PubMed

Burwell, R Geoffrey; Dangerfield, Peter H; Freeman, Brian J C

2008-01-01

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). Encouraging advances thought to be related to AIS pathogenesis have recently been made in several fields including anthropometry of bone growth, bone mass, spinal growth modulation, extra-spinal left-right skeletal length asymmetries and disproportions, magnetic resonance imaging of vertebral column, spinal cord, brain, skull, and molecular pathogenesis. These advances are leading to the evaluation of new treatments including attempts at minimally invasive surgery on the spine and peri-apical ribs. Several concepts of AIS are outlined indicating their clinical applications but not their research potential. The concepts, by derivation morphological, molecular and mathematical, are addressed in 15 sections: 1) initiating and progressive factors; 2) relative anterior spinal overgrowth; 3) dorsal shear forces that create axial rotational instability; 4) rotational preconstraint; 5) uncoupled, or asynchronous, spinal neuro-osseous growth; 6) brain, nervous system and skull; 7) a novel neuro-osseous escalator concept based on a putative abnormality of two normal polarized processes namely, a) increasing skeletal dimensions, and b) the CNS body schema - both contained within a neuro-osseous timing of maturation (NOTOM) concept; 8) transverse plane pelvic rotation, skeletal asymmetries and developmental theory; 9) thoraco-spinal concept; 10) origin in contracture at the hips; 11) osteopenia; 12) melatonin deficiency; 13) systemic melatonin-signaling pathway dysfunction; 14) platelet calmodulin dysfunction; and 15) biomechanical spinal growth modulation. From these concepts, a collective model for AIS pathogenesis is formulated. The central concept of this model includes the body schema of the neural systems, widely-studied in adults, that control normal posture and coordinated movements with frames of reference in the posterior parietal cortex. The escalator concept has implications for the normal development of upright posture, and the evolution in humans of neural control, the trunk and unique bipedal gait.

Organization of left–right coordination of neuronal activity in the mammalian spinal cord: Insights from computational modelling

PubMed Central

Shevtsova, Natalia A; Talpalar, Adolfo E; Markin, Sergey N; Harris-Warrick, Ronald M; Kiehn, Ole; Rybak, Ilya A

2015-01-01

Different locomotor gaits in mammals, such as walking or galloping, are produced by coordinated activity in neuronal circuits in the spinal cord. Coordination of neuronal activity between left and right sides of the cord is provided by commissural interneurons (CINs), whose axons cross the midline. In this study, we construct and analyse two computational models of spinal locomotor circuits consisting of left and right rhythm generators interacting bilaterally via several neuronal pathways mediated by different CINs. The CIN populations incorporated in the models include the genetically identified inhibitory (V0D) and excitatory (V0V) subtypes of V0 CINs and excitatory V3 CINs. The model also includes the ipsilaterally projecting excitatory V2a interneurons mediating excitatory drive to the V0V CINs. The proposed network architectures and CIN connectivity allow the models to closely reproduce and suggest mechanistic explanations for several experimental observations. These phenomena include: different speed-dependent contributions of V0D and V0V CINs and V2a interneurons to left–right alternation of neural activity, switching gaits between the left–right alternating walking-like activity and the left–right synchronous hopping-like pattern in mutants lacking specific neuron classes, and speed-dependent asymmetric changes of flexor and extensor phase durations. The models provide insights into the architecture of spinal network and the organization of parallel inhibitory and excitatory CIN pathways and suggest explanations for how these pathways maintain alternating and synchronous gaits at different locomotor speeds. The models propose testable predictions about the neural organization and operation of mammalian locomotor circuits. Key points Coordination of neuronal activity between left and right sides of the mammalian spinal cord is provided by several sets of commissural interneurons (CINs) whose axons cross the midline. Genetically identified inhibitory V0D and excitatory V0V CINs and ipsilaterally projecting excitatory V2a interneurons were shown to secure left–right alternation at different locomotor speeds. We have developed computational models of neuronal circuits in the spinal cord that include left and right rhythm-generating centres interacting bilaterally via three parallel pathways mediated by V0D, V2a–V0V and V3 neuron populations. The models reproduce the experimentally observed speed-dependent left–right coordination in normal mice and the changes in coordination seen in mutants lacking specific neuron classes. The models propose an explanation for several experimental results and provide insights into the organization of the spinal locomotor network and parallel CIN pathways involved in gait control at different locomotor speeds. PMID:25820677

Intraperitoneally administered IgG from patients with amyotrophic lateral sclerosis or from an immune-mediated goat model increase the levels of TNF-α, IL-6, and IL-10 in the spinal cord and serum of mice.

PubMed

Obál, Izabella; Klausz, Gergely; Mándi, Yvette; Deli, Mária; Siklós, László; Engelhardt, József I

2016-05-24

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that involves the selective loss of the upper and lower motor neurons (MNs). Neuroinflammation has been implicated in the pathogenesis of the sporadic form of the disease. We earlier developed immune-mediated animal models of ALS and demonstrated humoral and cellular immune reactions in the nervous system and in the sera of patients and animals. The accumulation of immunoglobulin G (IgG), an elevated intracellular level of calcium, ultrastructural alterations in the MNs, and activation of the microglia were noted in the spinal cord of ALS patients. Similar alterations developed in mice inoculated intraperitoneally with IgG from ALS patients or from an immune-mediated goat model. We have now examined whether the intraperitoneal injection of mice with IgG from sporadic ALS patients or from immunized goats with the homogenate of the anterior horn of the bovine spinal cord is associated with changes in the pro-inflammatory (TNF-α and IL-6) and anti-inflammatory (IL-10) cytokines in the spinal cord and serum of the mice. The levels of cytokines were measured by ELISA. Intraperitoneally administered IgG from the ALS patients induced subclinical signs of MN disease, while the injection of IgG from immunized goats resulted in a severe respiratory dysfunction and limb paralysis 24 h after the injections. Significantly increased levels of TNF-α and IL-10 were detected in the spinal cord of the mice injected with the human ALS IgG. The level of IL-6 increased primarily in the serum. The IgG from the immunized goats induced highly significant increases in the levels of all three cytokines in the serum and the spinal cord of mice. Our earlier experiments had proved that when ALS IgG or IgG from immune-mediated animal models was inoculated into mice, it was taken up in the MNs and had the ability to initiate damage in them. The pathological process was paralleled by microglia recruitment and activation in the spinal cord. The present experiment revealed that these forms of IgG cause significant increases in certain cytokine levels locally in the spinal cord and in the serum of the inoculated mice. These results suggest that IgG directed to the MNs may be an initial element in the damage to the MNs both in human ALS and in its immune-mediated animal models.

7 Tesla 22-channel wrap-around coil array for cervical spinal cord and brainstem imaging.

PubMed

Zhang, Bei; Seifert, Alan C; Kim, Joo-Won; Borrello, Joseph; Xu, Junqian

2017-10-01

Increased signal-to-noise ratio and blood oxygenation level-dependent sensitivity at 7 Tesla (T) have the potential to enable high-resolution imaging of the human cervical spinal cord and brainstem. We propose a new two-panel radiofrequency coil design for these regions to fully exploit the advantages of ultra-high field. A two-panel array, containing four transmit/receive and 18 receive-only elements fully encircling the head and neck, was constructed following simulations demonstrating the B1+ and specific absorption rate (SAR) benefits of two-panel over one-panel arrays. This array was compared with a previously reported posterior-only array and tested for safety using a phantom. Its anatomical, functional, and diffusion MRI performance was demonstrated in vivo. The two-panel array produced more uniform B1+ across the brainstem and cervical spinal cord without compromising SAR, and achieved 70% greater receive sensitivity than the posterior-only array. The two-panel design enabled acceleration of R = 2 × 2 in two dimensions or R = 3 in a single dimension. High quality in vivo anatomical, functional, and diffusion images of the human cervical spinal cord and brainstem were acquired. We have designed and constructed a wrap-around coil array with excellent performance for cervical spinal cord and brainstem MRI at 7T, which enables simultaneous human cervical spinal cord and brainstem functional MRI. Magn Reson Med 78:1623-1634, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Descending propriospinal neurons mediate restoration of locomotor function following spinal cord injury

PubMed Central

Benthall, Katelyn N.; Hough, Ryan A.

2016-01-01

Following spinal cord injury (SCI) in the lamprey, there is virtually complete recovery of locomotion within a few weeks, but interestingly, axonal regeneration of reticulospinal (RS) neurons is mostly limited to short distances caudal to the injury site. To explain this situation, we hypothesize that descending propriospinal (PS) neurons relay descending drive from RS neurons to indirectly activate spinal central pattern generators (CPGs). In the present study, the contributions of PS neurons to locomotor recovery were tested in the lamprey following SCI. First, long RS neuron projections were interrupted by staggered spinal hemitransections on the right side at 10% body length (BL; normalized from the tip of the oral hood) and on the left side at 30% BL. For acute recovery conditions (≤1 wk) and before axonal regeneration, swimming muscle burst activity was relatively normal, but with some deficits in coordination. Second, lampreys received two spaced complete spinal transections, one at 10% BL and one at 30% BL, to interrupt long-axon RS neuron projections. At short recovery times (3–5 wk), RS and PS neurons will have regenerated their axons for short distances and potentially established a polysynaptic descending command pathway. At these short recovery times, swimming muscle burst activity had only minor coordination deficits. A computer model that incorporated either of the two spinal lesions could mimic many aspects of the experimental data. In conclusion, descending PS neurons are a viable mechanism for indirect activation of spinal locomotor CPGs, although there can be coordination deficits of locomotor activity. NEW & NOTEWORTHY In the lamprey following spinal lesion-mediated interruption of long axonal projections of reticulospinal (RS) neurons, sensory stimulation still elicited relatively normal locomotor muscle burst activity, but with some coordination deficits. Computer models incorporating the spinal lesions could mimic many aspects of the experimental results. Thus, after disruption of long-axon projections from RS neurons in the lamprey, descending propriospinal (PS) neurons appear to be a viable compensatory mechanism for indirect activation of spinal locomotor networks. PMID:27760818

Descending propriospinal neurons mediate restoration of locomotor function following spinal cord injury.

PubMed

Benthall, Katelyn N; Hough, Ryan A; McClellan, Andrew D

2017-01-01

Following spinal cord injury (SCI) in the lamprey, there is virtually complete recovery of locomotion within a few weeks, but interestingly, axonal regeneration of reticulospinal (RS) neurons is mostly limited to short distances caudal to the injury site. To explain this situation, we hypothesize that descending propriospinal (PS) neurons relay descending drive from RS neurons to indirectly activate spinal central pattern generators (CPGs). In the present study, the contributions of PS neurons to locomotor recovery were tested in the lamprey following SCI. First, long RS neuron projections were interrupted by staggered spinal hemitransections on the right side at 10% body length (BL; normalized from the tip of the oral hood) and on the left side at 30% BL. For acute recovery conditions (≤1 wk) and before axonal regeneration, swimming muscle burst activity was relatively normal, but with some deficits in coordination. Second, lampreys received two spaced complete spinal transections, one at 10% BL and one at 30% BL, to interrupt long-axon RS neuron projections. At short recovery times (3-5 wk), RS and PS neurons will have regenerated their axons for short distances and potentially established a polysynaptic descending command pathway. At these short recovery times, swimming muscle burst activity had only minor coordination deficits. A computer model that incorporated either of the two spinal lesions could mimic many aspects of the experimental data. In conclusion, descending PS neurons are a viable mechanism for indirect activation of spinal locomotor CPGs, although there can be coordination deficits of locomotor activity. In the lamprey following spinal lesion-mediated interruption of long axonal projections of reticulospinal (RS) neurons, sensory stimulation still elicited relatively normal locomotor muscle burst activity, but with some coordination deficits. Computer models incorporating the spinal lesions could mimic many aspects of the experimental results. Thus, after disruption of long-axon projections from RS neurons in the lamprey, descending propriospinal (PS) neurons appear to be a viable compensatory mechanism for indirect activation of spinal locomotor networks. Copyright © 2017 the American Physiological Society.

Assessment of physiological noise modelling methods for functional imaging of the spinal cord.

PubMed

Kong, Yazhuo; Jenkinson, Mark; Andersson, Jesper; Tracey, Irene; Brooks, Jonathan C W

2012-04-02

The spinal cord is the main pathway for information between the central and the peripheral nervous systems. Non-invasive functional MRI offers the possibility of studying spinal cord function and central sensitisation processes. However, imaging neural activity in the spinal cord is more difficult than in the brain. A significant challenge when dealing with such data is the influence of physiological noise (primarily cardiac and respiratory), and currently there is no standard approach to account for these effects. We have previously studied the various sources of physiological noise for spinal cord fMRI at 1.5T and proposed a physiological noise model (PNM) (Brooks et al., 2008). An alternative de-noising strategy, selective averaging filter (SAF), was proposed by Deckers et al. (2006). In this study we reviewed and implemented published physiological noise correction methods at higher field (3T) and aimed to find the optimal models for gradient-echo-based BOLD acquisitions. Two general techniques were compared: physiological noise model (PNM) and selective averaging filter (SAF), along with regressors designed to account for specific signal compartments and physiological processes: cerebrospinal fluid (CSF), motion correction (MC) parameters, heart rate (HR), respiration volume per time (RVT), and the associated cardiac and respiratory response functions. Functional responses were recorded from the cervical spinal cord of 18 healthy subjects in response to noxious thermal and non-noxious punctate stimulation. The various combinations of models and regressors were compared in three ways: the model fit residuals, regression model F-tests and the number of activated voxels. The PNM was found to outperform SAF in all three tests. Furthermore, inclusion of the CSF regressor was crucial as it explained a significant amount of signal variance in the cord and increased the number of active cord voxels. Whilst HR, RVT and MC explained additional signal (noise) variance, they were also found (in particular HR and RVT) to have a negative impact on the parameter estimates (of interest)--as they may be correlated with task conditions e.g. noxious thermal stimuli. Convolution with previously published cardiac and respiratory impulse response functions was not found to be beneficial. The other novel aspect of current study is the investigation of the influence of pre-whitening together with PNM regressors on spinal fMRI data. Pre-whitening was found to reduce non-white noise, which was not accounted for by physiological noise correction, and decrease false positive detection rates. Copyright © 2011 Elsevier Inc. All rights reserved.

Topiramate as a neuroprotective agent in a rat model of spinal cord injury.

PubMed

Narin, Firat; Hanalioglu, Sahin; Ustun, Huseyin; Kilinc, Kamer; Bilginer, Burcak

2017-12-01

Topiramate (TPM) is a widely used antiepileptic and antimigraine agent which has been shown to exert neuroprotective effects in various experimental traumatic brain injury and stroke models. However, its utility in spinal cord injury has not been studied extensively. Thus, we evaluated effects of TPM on secondary cellular injury mechanisms in an experimental rat model of traumatic spinal cord injury (SCI). After rat models of thoracic contusive SCI were established by free weight-drop method, TPM (40 mg/kg) was given at 12-hour intervals for four times orally. Post TPM treatment, malondialdehyde and protein carbonyl levels were significantly reduced and reduced glutathione levels were increased, while immunoreactivity for endothelial nitric oxide synthase, inducible nitric oxide synthase, and apoptotic peptidase activating factor 1 was diminished in SCI rats. In addition, TPM treatment improved the functional recovery of SCI rats. This study suggests that administration of TPM exerts neuroprotective effects on SCI.

Functional status predicts acute care readmission in the traumatic spinal cord injury population.

PubMed

Huang, Donna; Slocum, Chloe; Silver, Julie K; Morgan, James W; Goldstein, Richard; Zafonte, Ross; Schneider, Jeffrey C

2018-03-29

Context/objective Acute care readmission has been identified as an important marker of healthcare quality. Most previous models assessing risk prediction of readmission incorporate variables for medical comorbidity. We hypothesized that functional status is a more robust predictor of readmission in the spinal cord injury population than medical comorbidities. Design Retrospective cross-sectional analysis. Setting Inpatient rehabilitation facilities, Uniform Data System for Medical Rehabilitation data from 2002 to 2012 Participants traumatic spinal cord injury patients. Outcome measures A logistic regression model for predicting acute care readmission based on demographic variables and functional status (Functional Model) was compared with models incorporating demographics, functional status, and medical comorbidities (Functional-Plus) or models including demographics and medical comorbidities (Demographic-Comorbidity). The primary outcomes were 3- and 30-day readmission, and the primary measure of model performance was the c-statistic. Results There were a total of 68,395 patients with 1,469 (2.15%) readmitted at 3 days and 7,081 (10.35%) readmitted at 30 days. The c-statistics for the Functional Model were 0.703 and 0.654 for 3 and 30 days. The Functional Model outperformed Demographic-Comorbidity models at 3 days (c-statistic difference: 0.066-0.096) and outperformed two of the three Demographic-Comorbidity models at 30 days (c-statistic difference: 0.029-0.056). The Functional-Plus models exhibited negligible improvements (0.002-0.010) in model performance compared to the Functional models. Conclusion Readmissions are used as a marker of hospital performance. Function-based readmission models in the spinal cord injury population outperform models incorporating medical comorbidities. Readmission risk models for this population would benefit from the inclusion of functional status.

Preclinical evidence supporting the clinical development of central pattern generator-modulating therapies for chronic spinal cord-injured patients

PubMed Central

2014-01-01

Ambulation or walking is one of the main gaits of locomotion. In terrestrial animals, it may be defined as a series of rhythmic and bilaterally coordinated movement of the limbs which creates a forward movement of the body. This applies regardless of the number of limbs—from arthropods with six or more limbs to bipedal primates. These fundamental similarities among species may explain why comparable neural systems and cellular properties have been found, thus far, to control in similar ways locomotor rhythm generation in most animal models. The aim of this article is to provide a comprehensive review of the known structural and functional features associated with central nervous system (CNS) networks that are involved in the control of ambulation and other stereotyped motor patterns—specifically Central Pattern Generators (CPGs) that produce basic rhythmic patterned outputs for locomotion, micturition, ejaculation, and defecation. Although there is compelling evidence of their existence in humans, CPGs have been most studied in reduced models including in vitro isolated preparations, genetically-engineered mice and spinal cord-transected animals. Compared with other structures of the CNS, the spinal cord is generally considered as being well-preserved phylogenetically. As such, most animal models of spinal cord-injured (SCI) should be considered as valuable tools for the development of novel pharmacological strategies aimed at modulating spinal activity and restoring corresponding functions in chronic SCI patients. PMID:24910602

The PPAR alpha agonist gemfibrozil is an ineffective treatment for spinal cord injured mice

PubMed Central

Almad, Akshata; Lash, A. Todd; Wei, Ping; Lovett-Racke, Amy E.; McTigue, Dana M.

2017-01-01

Peroxisome Proliferator Activated Receptor (PPAR)-α is a key regulator of lipid metabolism and recent studies reveal it also regulates inflammation in several different disease models. Gemfibrozil, an agonist of PPAR-α, is a FDA approved drug for hyperlipidemia and has been shown to inhibit clinical signs in a rodent model of multiple sclerosis. Since many studies have shown improved outcome from spinal cord injury (SCI) by anti-inflammatory and neuroprotective agents, we tested the efficacy of oral gemfibrozil given before or after SCI for promoting tissue preservation and behavioral recovery after spinal contusion injury in mice. Unfortunately, the results were contrary to our hypothesis; in our first attempt, gemfibrozil treatment exacerbated locomotor deficits and increased tissue pathology after SCI. In subsequent experiments, the behavioral effects were not replicated but histological outcomes again were worse. We also tested the efficacy of a different PPAR-α agonist, fenofibrate, which also modulates immune responses and is beneficial in several neurodegenerative disease models. Fenofibrate treatment did not improve recovery, although there was a slight trend for a modest increase in histological tissue sparing. Based on our results, we conclude that PPAR-α agonists yield either no effect or worsen recovery from spinal cord injury, at least at the doses and the time points of drug delivery tested here. Further, patients sustaining spinal cord injury while taking gemfibrozil might be prone to exacerbated tissue damage. PMID:21963672

The volatile anesthetic methoxyflurane protects motoneurons against excitotoxicity in an in vitro model of rat spinal cord injury.

PubMed

Shabbir, A; Bianchetti, E; Nistri, A

2015-01-29

Neuroprotection of the spinal cord during the early phase of injury is an important goal to determine a favorable outcome by prevention of delayed pathological events, including excitotoxicity, which otherwise extend the primary damage and amplify the often irreversible loss of motor function. While intensive care and neurosurgical intervention are important treatments, effective neuroprotection requires further experimental studies focused to target vulnerable neurons, particularly motoneurons. The present investigation examined whether the volatile general anesthetic methoxyflurane might protect spinal locomotor networks from kainate-evoked excitotoxicity using an in vitro rat spinal cord preparation as a model. The protocols involved 1h excitotoxic stimulation on day 1 followed by electrophysiological and immunohistochemical testing on day 2. A single administration of methoxyflurane applied together with kainate (1h), or 30 or even 60 min later prevented any depression of spinal reflexes, loss of motoneuron excitability, and histological damage. Methoxyflurane per se temporarily decreased synaptic transmission and motoneuron excitability, effects readily reversible on washout. Spinal locomotor activity recorded as alternating electrical discharges from lumbar motor pools was fully preserved on the second day after application of methoxyflurane together with (or after) kainate. These data suggest that a volatile general anesthetic could provide strong electrophysiological and histological neuroprotection that enabled expression of locomotor network activity 1 day after the excitotoxic challenge. It is hypothesized that the benefits of early neurosurgery for acute spinal cord injury (SCI) might be enhanced if, in addition to injury decompression and stabilization, the protective role of general anesthesia is exploited. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Spinal Actions of Lipoxin A4 and 17(R)-Resolvin D1 Attenuate Inflammation-Induced Mechanical Hypersensitivity and Spinal TNF Release

PubMed Central

Abdelmoaty, Sally; Wigerblad, Gustaf; Bas, Duygu B.; Codeluppi, Simone; Fernandez-Zafra, Teresa; El-Awady, El-Sayed; Moustafa, Yasser; Abdelhamid, Alaa El-din S.; Brodin, Ernst; Svensson, Camilla I.

2013-01-01

Lipoxins and resolvins have anti-inflammatory and pro-resolving actions and accumulating evidence indicates that these lipid mediators also attenuate pain-like behavior in a number of experimental models of inflammation and tissue injury-induced pain. The present study was undertaken to assess if spinal administration of lipoxin A4 (LXA4) or 17 (R)-resolvin D1 (17(R)-RvD1) attenuates mechanical hypersensitivity in the carrageenan model of peripheral inflammation in the rat. Given the emerging role of spinal cytokines in the generation and maintenance of inflammatory pain we measured cytokine levels in the cerebrospinal fluid (CSF) after LXA4 or 17(R)-RvD1 administration, and the ability of these lipid metabolites to prevent stimuli-induced release of cytokines from cultured primary spinal astrocytes. We found that intrathecal bolus injection of LXA4 and17(R)-RvD1 attenuated inflammation-induced mechanical hypersensitivity without reducing the local inflammation. Furthermore, both LXA4 and 17(R)-RvD1 reduced carrageenan-induced tumor necrosis factor (TNF) release in the CSF, while only 17(R)-RvD1attenuated LPS and IFN-γ-induced TNF release in astrocyte cell culture. In conclusion, this study demonstrates that lipoxins and resolvins potently suppress inflammation-induced mechanical hypersensitivity, possibly by attenuating cytokine release from spinal astrocytes. The inhibitory effect of lipoxins and resolvins on spinal nociceptive processing puts them in an intriguing position in the search for novel pain therapeutics. PMID:24086560

Increased phospho-adducin immunoreactivity in a murine model of amyotrophic lateral sclerosis.

PubMed

Shan, X; Hu, J H; Cayabyab, F S; Krieger, C

2005-01-01

Adducins alpha, beta and gamma are proteins that link spectrin and actin in the regulation of cytoskeletal architecture and are substrates for protein kinase C and other signaling molecules. Previous studies have shown that expressions of phosphorylated adducin (phospho-adducin) and protein kinase C are increased in spinal cord tissue from patients who died with amyotrophic lateral sclerosis, a neurodegenerative disorder of motoneurons and other cells. However, the distribution of phospho-adducin immunoreactivity has not been described in the mammalian spinal cord. We have evaluated the distribution of immunoreactivity to serine/threonine-dependent phospho-adducin at a region corresponding to the myristoylated alanine-rich C kinase substrate-related domain of adducin in spinal cords of mice over-expressing mutant human superoxide dismutase, an animal model of amyotrophic lateral sclerosis, and in control littermates. We find phospho-adducin immunoreactivity in control spinal cord in ependymal cells surrounding the central canal, neurons and astrocytes. Phospho-adducin immunoreactivity is localized to the cell bodies, dendrites and axons of some motoneurons, as well as to astrocytes in the gray and white matter. Spinal cords of mutant human superoxide dismutase mice having motoneuron loss exhibit significantly increased phospho-adducin immunoreactivity in ventral and dorsal horn spinal cord regions, but not in ependyma surrounding the central canal, compared with control animals. Increased phospho-adducin immunoreactivity localizes predominantly to astrocytes and likely increases as a consequence of the astrogliosis that occurs in the mutant human superoxide dismutase mouse with disease progression. These findings demonstrate increased immunoreactivity against phosphorylated adducin at the myristoylated alanine-rich C kinase substrate domain in a murine model of amyotrophic lateral sclerosis. As adducin is a substrate for protein kinase C at the myristoylated alanine-rich C kinase substrate domain, the increased phospho-adducin immunoreactivity is likely a consequence of protein kinase C activation in neurons and astrocytes of the spinal cord and evidence for aberrant phosphorylation events in mutant human superoxide dismutase mice that may affect neuron survival.

Electroacupuncture attenuates mechanical allodynia by suppressing the spinal JNK1/2 pathway in a rat model of inflammatory pain.

PubMed

Du, Jun-Ying; Fang, Jian-Qiao; Liang, Yi; Fang, Jun-Fan

2014-09-01

Electroacupuncture (EA) has a substantial analgesic effect on inflammatory pain induced by complete Freund's adjuvant (CFA). The activation of the c-Jun N-terminal kinase 1/2 (JNK1/2) signal transduction pathway in the spinal cord is associated with inflammatory pain. However, the relationship between EA's analgesic effect and the JNK1/2 signal transduction pathway in the inflammatory pain remain unclear. In the present study, we used the established rat model of CFA-induced inflammatory pain to investigate the role of the spinal JNK1/2 pathway in EA-mediated analgesia. We observed a decrease in paw withdrawal thresholds and an increase in paw edema at 1 and 3 days after injecting CFA into the right hindpaw. CFA, 3 days after injection, upregulated expression of phospho-c-Jun N-terminal kinase1/2 (p-JNK1/2) protein and its downstream targets, the transcriptional regulators p-c-Jun and activator protein-1 (AP-1), as well as cyclooxygenase-2 (COX-2) and the transient receptor potential vanilloid 1 (TRPV1). EA significantly alleviated CFA-induced inflammatory pain. In addition, EA reduced p-JNK1/2 protein levels and COX-2 mRNA expressions, a degree of down-regulated p-c-Jun protein level and AP-1 DNA binding activity in the spinal dorsal horn of CFA-administered animals, but it had no effect on TRPV1 mRNA expression. Furthermore, EA and the JNK inhibitor SP600125 synergistically inhibited CFA-induced hyperalgesia and suppressed the COX-2 mRNA expression in the spinal dorsal horn. Our findings indicate that EA alleviates inflammatory pain behavior, at least in part, by reducing COX-2 expression in the spinal cord via the JNK1/2 signaling pathway. Inactivation of the spinal JNK1/2 signal transduction pathway maybe the potential mechanism of EA's antinociception in the inflammatory pain model. Copyright © 2014 Elsevier Inc. All rights reserved.

Overcoming the tyranny of distance: An audit of process and outcomes from a pilot telehealth spinal assessment clinic.

PubMed

Beard, Matthew; Orlando, Joseph F; Kumar, Saravana

2017-09-01

Introduction There is consistent evidence to indicate people living in rural and remote regions have limited access to healthcare and poorer health outcomes. One way to address this inequity is through innovative models of care such as telehealth. The aim of this pilot trial was to determine the feasibility, appropriateness and access to a telehealth clinic. In this pilot trial, the telehealth clinic outcomes are compared with the outreach clinic. Both models of care are commonly utilised means of providing healthcare to meet the needs of people living in rural and remote regions. Methods A prospective audit was conducted on a Spinal Assessment Clinic Telehealth pilot trial for patients with spinal disorders requiring non-urgent surgical consultation. Data were recorded from all consultations managed using videoconferencing technology between the Royal Adelaide Hospital and Port Augusta Community Health Service, South Australia between September 2013 and January 2014. Outcomes included analysis of process, service activity, clinical actions, safety and costs. Data were compared to a previous spinal assessment outreach clinic in the same area between August and December 2012. Results There were 25 consultations with 22 patients over the five-month telehealth pilot trial. Spinal disorders were predominantly of the lumbar region (88%); the majority of initial consultations (64%) were discharged to the general practitioner. There were three requests for further imaging, five for minor interventions and three for other specialist/surgical consultation. Patient follow-up post telehealth pilot trial revealed no adverse outcomes. The total cost of AUD$11,187 demonstrated a 23% reduction in favour of the spinal assessment telehealth pilot trial, with the greatest savings in travel costs. Discussion The telehealth model of care demonstrated the efficient management of patients with spinal disorders in rural regions requiring non-urgent surgical consultation at low costs with no adverse outcomes reported.

Nanog interact with CDK6 to regulates astrocyte cells proliferation following spinal cord injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gu, Jun; Department of Orthopaedics, Xishan People's Hospital, Wuxi, Jiangsu; Ni, Yingjie

2016-01-22

Previous research had reported transcription factors Nanog expressed in pluripotent embryonic stem cells (ESCS) that played an important role in regulating the cell proliferation. Nanog levels are frequently elevated in ESCS, but the role in the spinal cord was not clear. To examine the biological relevance of Nanog, we studied its properties in spinal cord injury model. The expression of Nanog and PCNA was gradually increased and reached a peak at 3 day by western blot analysis. The expression of Nanog was further analyzed by immunohistochemistry. Double immunofluorescent staining uncovered that Nanog can co-labeled with PCNA and GFAP in themore » spinal cord tissue. In vitro, Nanog can promote the proliferation of astrocyte cell by Fluorescence Activating Cell Sorter (FACS) and CCK8. Meanwhile, the cell-cycle protein CDK6 could interact with Nanog in the spinal cord tissue. Taken together, these data suggested that both Nanog may play important roles in spinal cord pathophysiology via interact with CDK6.« less

Sacroiliac Joint Fusion Minimally Affects Adjacent Lumbar Segment Motion: A Finite Element Study

PubMed Central

Kiapour, Ali; Yerby, Scott A.; Goel, Vijay K.

2015-01-01

Background Adjacent segment disease is a recognized consequence of fusion in the spinal column. Fusion of the sacroiliac joint is an effective method of pain reduction. Although effective, the consequences of sacroiliac joint fusion and the potential for adjacent segment disease for the adjacent lumbar spinal levels is unknown. The objective of this study was to quantify the change in range of motion of the sacroiliac joint and the adjacent lumbar spinal motion segments due to sacroiliac joint fusion and compare these changes to previous literature to assess the potential for adjacent segment disease in the lumbar spine. Methods An experimentally validated finite element model of the lumbar spine and pelvis was used to simulate a fusion of the sacroiliac joint using three laterally placed triangular implants (iFuse Implant System, SI-BONE, Inc., San Jose, CA). The range of motion of the sacroiliac joint and the adjacent lumbar spinal motion segments were calculated using a hybrid loading protocol and compared with the intact range of motion in flexion, extension, lateral bending, and axial rotation. Results The range of motions of the treated sacroiliac joints were reduced in flexion, extension, lateral bending, and axial rotation, by 56.6%, 59.5%, 27.8%, and 53.3%, respectively when compared with the intact condition. The stiffening of the sacroiliac joint resulted in increases at the adjacent lumbar motion segment (L5-S1) for flexion, extension, lateral bending, and axial rotation, of 3.0%, 3.7%, 1.1%, and 4.6%, respectively. Conclusions Fusion of the sacroiliac joint resulted in substantial (> 50%) reductions in flexion, extension, and axial rotation of the sacroiliac joint with minimal (< 5%) increases in range of motion in the lumbar spine. Although the predicted increases in lumbar range of motion are minimal after sacroiliac joint fusion, the long-term clinical results remain to be investigated. PMID:26767156

Sacroiliac Joint Fusion Minimally Affects Adjacent Lumbar Segment Motion: A Finite Element Study.

PubMed

Lindsey, Derek P; Kiapour, Ali; Yerby, Scott A; Goel, Vijay K

2015-01-01

Adjacent segment disease is a recognized consequence of fusion in the spinal column. Fusion of the sacroiliac joint is an effective method of pain reduction. Although effective, the consequences of sacroiliac joint fusion and the potential for adjacent segment disease for the adjacent lumbar spinal levels is unknown. The objective of this study was to quantify the change in range of motion of the sacroiliac joint and the adjacent lumbar spinal motion segments due to sacroiliac joint fusion and compare these changes to previous literature to assess the potential for adjacent segment disease in the lumbar spine. An experimentally validated finite element model of the lumbar spine and pelvis was used to simulate a fusion of the sacroiliac joint using three laterally placed triangular implants (iFuse Implant System, SI-BONE, Inc., San Jose, CA). The range of motion of the sacroiliac joint and the adjacent lumbar spinal motion segments were calculated using a hybrid loading protocol and compared with the intact range of motion in flexion, extension, lateral bending, and axial rotation. The range of motions of the treated sacroiliac joints were reduced in flexion, extension, lateral bending, and axial rotation, by 56.6%, 59.5%, 27.8%, and 53.3%, respectively when compared with the intact condition. The stiffening of the sacroiliac joint resulted in increases at the adjacent lumbar motion segment (L5-S1) for flexion, extension, lateral bending, and axial rotation, of 3.0%, 3.7%, 1.1%, and 4.6%, respectively. Fusion of the sacroiliac joint resulted in substantial (> 50%) reductions in flexion, extension, and axial rotation of the sacroiliac joint with minimal (< 5%) increases in range of motion in the lumbar spine. Although the predicted increases in lumbar range of motion are minimal after sacroiliac joint fusion, the long-term clinical results remain to be investigated.

Multilevel Analysis of Locomotion in Immature Preparations Suggests Innovative Strategies to Reactivate Stepping after Spinal Cord Injury.

PubMed

Brumley, Michele R; Guertin, Pierre A; Taccola, Giuliano

2017-01-01

Locomotion is one of the most complex motor behaviors. Locomotor patterns change during early life, reflecting development of numerous peripheral and hierarchically organized central structures. Among them, the spinal cord is of particular interest since it houses the central pattern generator (CPG) for locomotion. This main command center is capable of eliciting and coordinating complex series of rhythmic neural signals sent to motoneurons and to corresponding target-muscles for basic locomotor activity. For a long-time, the CPG has been considered a black box. In recent years, complementary insights from in vitro and in vivo animal models have contributed significantly to a better understanding of its constituents, properties and ways to recover locomotion after a spinal cord injury (SCI). This review discusses key findings made by comparing the results of in vitro isolated spinal cord preparations and spinal-transected in vivo models from neonatal animals. Pharmacological, electrical, and sensory stimulation approaches largely used to further understand CPG function may also soon become therapeutic tools for potent CPG reactivation and locomotor movement induction in persons with SCI or developmental neuromuscular disorder. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Three Element Phased Array Coil for Imaging of Rat Spinal Cord at 7T

PubMed Central

Mogatadakala, Kishore V.; Bankson, James A.; Narayana, Ponnada A.

2008-01-01

In order to overcome some of the limitations of an implantable coil, including its invasive nature and limited spatial coverage, a three element phased array coil is described for high resolution magnetic resonance imaging (MRI) of rat spinal cord. This coil allows imaging both thoracic and cervical segments of rat spinal cord. In the current design, coupling between the nearest neighbors was minimized by overlapping the coil elements. A simple capacitive network was used for decoupling the next neighbor elements. The dimensions of individual coils in the array were determined based on the signal-to-noise ratio (SNR) measurements performed on a phantom with three different surface coils. SNR measurements on a phantom demonstrated higher SNR of the phased array coil relative to two different volume coils. In-vivo images acquired on rat spinal cord with our coil demonstrated excellent gray and white matter contrast. To evaluate the performance of the phased array coil under parallel imaging, g-factor maps were obtained for two different acceleration factors of 2 and 3. These simulations indicate that parallel imaging with acceleration factor of 2 would be possible without significant image reconstruction related noise amplifications. PMID:19025892

Edaravone is a candidate agent for spinal muscular atrophy: In vitro analysis using a human induced pluripotent stem cells-derived disease model.

PubMed

Ando, Shiori; Funato, Michinori; Ohuchi, Kazuki; Kameyama, Tsubasa; Inagaki, Satoshi; Seki, Junko; Kawase, Chizuru; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Kaneko, Hideo; Hara, Hideaki

2017-11-05

Spinal muscular atrophy (SMA) is an intractable disease characterized by a progressive loss of spinal motor neurons, which leads to skeletal muscle weakness and atrophy. Currently, there are no curative agents for SMA, although it is understood to be caused by reduced levels of survival motor neuron (SMN) protein. Additionally, why reduced SMN protein level results in selective apoptosis in spinal motor neurons is still not understood. Our purpose in this study was to evaluate the therapeutic potential of edaravone, a free radical scavenger, by using induced pluripotent stem cells from an SMA patient (SMA-iPSCs) and to address oxidative stress-induced apoptosis in spinal motor neurons. We first found that edaravone could improve impaired neural development of SMA-iPSCs-derived spinal motor neurons with limited effect on nuclear SMN protein expression. Furthermore, edaravone inhibited the generation of reactive oxygen species and mitochondrial reactive oxygen species upregulated in SMA-iPSCs-derived spinal motor neurons, and reversed oxidative-stress induced apoptosis. In this study, we suggest that oxidative stress might be partly the reason for selective apoptosis in spinal motor neurons in SMA pathology, and that oxidative stress-induced apoptosis might be the therapeutic target of SMA. Copyright © 2017 Elsevier B.V. All rights reserved.

Exercise Preconditioning Protects against Spinal Cord Injury in Rats by Upregulating Neuronal and Astroglial Heat Shock Protein 72

PubMed Central

Chang, Cheng-Kuei; Chou, Willy; Lin, Hung-Jung; Huang, Yi-Ching; Tang, Ling-Yu; Lin, Mao-Tsun; Chang, Ching-Ping

2014-01-01

The heat shock protein 72 (HSP 72) is a universal marker of stress protein whose expression can be induced by physical exercise. Here we report that, in a localized model of spinal cord injury (SCI), exercised rats (given pre-SCI exercise) had significantly higher levels of neuronal and astroglial HSP 72, a lower functional deficit, fewer spinal cord contusions, and fewer apoptotic cells than did non-exercised rats. pSUPER plasmid expressing HSP 72 small interfering RNA (SiRNA-HSP 72) was injected into the injured spinal cords. In addition to reducing neuronal and astroglial HSP 72, the (SiRNA-HSP 72) significantly attenuated the beneficial effects of exercise preconditioning in reducing functional deficits as well as spinal cord contusion and apoptosis. Because exercise preconditioning induces increased neuronal and astroglial levels of HSP 72 in the gray matter of normal spinal cord tissue, exercise preconditioning promoted functional recovery in rats after SCI by upregulating neuronal and astroglial HSP 72 in the gray matter of the injured spinal cord. We reveal an important function of neuronal and astroglial HSP 72 in protecting neuronal and astroglial apoptosis in the injured spinal cord. We conclude that HSP 72-mediated exercise preconditioning is a promising strategy for facilitating functional recovery from SCI. PMID:25334068

Zebrafish In Situ Spinal Cord Preparation for Electrophysiological Recordings from Spinal Sensory and Motor Neurons

PubMed Central

Moreno, Rosa L.; Josey, Megan; Ribera, Angeles B.

2017-01-01

Zebrafish, first introduced as a developmental model, have gained popularity in many other fields. The ease of rearing large numbers of rapidly developing organisms, combined with the embryonic optical clarity, served as initial compelling attributes of this model. Over the past two decades, the success of this model has been further propelled by its amenability to large-scale mutagenesis screens and by the ease of transgenesis. More recently, gene-editing approaches have extended the power of the model. For neurodevelopmental studies, the zebrafish embryo and larva provide a model to which multiple methods can be applied. Here, we focus on methods that allow the study of an essential property of neurons, electrical excitability. Our preparation for the electrophysiological study of zebrafish spinal neurons involves the use of veterinarian suture glue to secure the preparation to a recording chamber. Alternative methods for recording from zebrafish embryos and larvae involve the attachment of the preparation to the chamber using a fine tungsten pin12345. A tungsten pin is most often used to mount the preparation in a lateral orientation, although it has been used to mount larvae dorsal-side up4. The suture glue has been used to mount embryos and larvae in both orientations. Using the glue, a minimal dissection can be performed, allowing access to spinal neurons without the use of an enzymatic treatment, thereby avoiding any resultant damage. However, for larvae, it is necessary to apply a brief enzyme treatment to remove the muscle tissue surrounding the spinal cord. The methods described here have been used to study the intrinsic electrical properties of motor neurons, interneurons, and sensory neurons at several developmental stages6789. PMID:28448016

Zebrafish In Situ Spinal Cord Preparation for Electrophysiological Recordings from Spinal Sensory and Motor Neurons.

PubMed

Moreno, Rosa L; Josey, Megan; Ribera, Angeles B

2017-04-18

Zebrafish, first introduced as a developmental model, have gained popularity in many other fields. The ease of rearing large numbers of rapidly developing organisms, combined with the embryonic optical clarity, served as initial compelling attributes of this model. Over the past two decades, the success of this model has been further propelled by its amenability to large-scale mutagenesis screens and by the ease of transgenesis. More recently, gene-editing approaches have extended the power of the model. For neurodevelopmental studies, the zebrafish embryo and larva provide a model to which multiple methods can be applied. Here, we focus on methods that allow the study of an essential property of neurons, electrical excitability. Our preparation for the electrophysiological study of zebrafish spinal neurons involves the use of veterinarian suture glue to secure the preparation to a recording chamber. Alternative methods for recording from zebrafish embryos and larvae involve the attachment of the preparation to the chamber using a fine tungsten pin 1 , 2 , 3 , 4 , 5 . A tungsten pin is most often used to mount the preparation in a lateral orientation, although it has been used to mount larvae dorsal-side up 4 . The suture glue has been used to mount embryos and larvae in both orientations. Using the glue, a minimal dissection can be performed, allowing access to spinal neurons without the use of an enzymatic treatment, thereby avoiding any resultant damage. However, for larvae, it is necessary to apply a brief enzyme treatment to remove the muscle tissue surrounding the spinal cord. The methods described here have been used to study the intrinsic electrical properties of motor neurons, interneurons, and sensory neurons at several developmental stages 6 , 7 , 8 , 9 .

Spinal motor control system incorporates an internal model of limb dynamics.

PubMed

Shimansky, Y P

2000-10-01

The existence and utilization of an internal representation of the controlled object is one of the most important features of the functioning of neural motor control systems. This study demonstrates that this property already exists at the level of the spinal motor control system (SMCS), which is capable of generating motor patterns for reflex rhythmic movements, such as locomotion and scratching, without the aid of the peripheral afferent feedback, but substantially modifies the generated activity in response to peripheral afferent stimuli. The SMCS is presented as an optimal control system whose optimality requires that it incorporate an internal model (IM) of the controlled object's dynamics. A novel functional mechanism for the integration of peripheral sensory signals with the corresponding predictive output from the IM, the summation of information precision (SIP) is proposed. In contrast to other models in which the correction of the internal representation of the controlled object's state is based on the calculation of a mismatch between the internal and external information sources, the SIP mechanism merges the information from these sources in order to optimize the precision of the controlled object's state estimate. It is demonstrated, based on scratching in decerebrate cats as an example of the spinal control of goal-directed movements, that the results of computer modeling agree with the experimental observations related to the SMCS's reactions to phasic and tonic peripheral afferent stimuli. It is also shown that the functional requirements imposed by the mathematical model of the SMCS comply with the current knowledge about the related properties of spinal neuronal circuitry. The crucial role of the spinal presynaptic inhibition mechanism in the neuronal implementation of SIP is elucidated. Important differences between the IM and a state predictor employed for compensating for a neural reflex time delay are discussed.

[The changes of monocarboxylate transporter-2 in spinal cord horn in a rat model of chronic inflammatory pain].

PubMed

He, Jian-hua; Xu, Li; Shen, Yu; Kong, Ming-jian; Shi, Lin-yu; Ma, Zheng-liang

2015-01-01

To investigate the changes in the levels of monocarboxylate transporter-2 in spinal cord horn in a rat model of chronic inflammatory pain. Male SD rats weighting 180 - 220 g were randomly divided into two groups(n = 48): normal saline group (NS group), complete Freund's adjuvant group (CFA group). Rats were given injections of CFA 100 µl in left hind paw in group CFA, and an equal volume of saline was given injection in group NS. Mechanical withdraw threshold(MWT) and thermal withdraw latency(TWL) were measured at before injection(T0 and 3 h, 1 d, 3 d, 7 d, 14 d, and 21 d after injection(T1-7). Four rats were chosen from each group at T0-7 and sacrificed, and L4-5 segments of the spinal cord horn were removed for measurement of the expression of monocarboxylate transporter-2 by Western blot analysis. In CFA group, mechanical hyperalgesia and allodynia appeared on the 3 h after CFA injection, then until the day 14. The expression of monocarboxylate transporter-2 in the spinal dorsal horn of rats in CFA group was significantly higher than that in normal control group at T1-6(P <0.05). The protein level of monocarboxylate transporter-2 was apparently correlated with MWT and TWL(P <0.01 and P <0.05) in CFA group. The level of monocarboxylate transporter-2 in spinal dorsal horn is significantly increased in a rat model of chronic inflammatory pain and the change may involve in the formation and maintenance of central sensitization in spinal cord of chronic inflammatory uain.

Improving the Efficiency and Efficacy of Glibenclamide in Limiting Progressive Hemorrhagic Necrosis Following Traumatic Spinal Cord Injury

DTIC Science & Technology

2014-12-01

glibenclamide reduces acute lesion expansion in a rat model of spinal cord injury. Simard JM, Popovich PG, Tsymbalyuk O, Caridi J , Gullapalli RP, Kilbourne MJ...ScienceDirect Experimental Neurology j ourna l homepage: www.e lsev ie r .com/ locate /yexnrSpinal cord injury with unilateral versus bilateral primary...hemorrhage — Effects of glibenclamide J . Marc Simard a,b,c,⁎, Phillip G. Popovich d, Orest Tsymbalyuk a, Volodymyr Gerzanich a a Department of

Mixed-reality simulation for neurosurgical procedures.

PubMed

Bova, Frank J; Rajon, Didier A; Friedman, William A; Murad, Gregory J; Hoh, Daniel J; Jacob, R Patrick; Lampotang, Samsun; Lizdas, David E; Lombard, Gwen; Lister, J Richard

2013-10-01

Surgical education is moving rapidly to the use of simulation for technical training of residents and maintenance or upgrading of surgical skills in clinical practice. To optimize the learning exercise, it is essential that both visual and haptic cues are presented to best present a real-world experience. Many systems attempt to achieve this goal through a total virtual interface. To demonstrate that the most critical aspect in optimizing a simulation experience is to provide the visual and haptic cues, allowing the training to fully mimic the real-world environment. Our approach has been to create a mixed-reality system consisting of a physical and a virtual component. A physical model of the head or spine is created with a 3-dimensional printer using deidentified patient data. The model is linked to a virtual radiographic system or an image guidance platform. A variety of surgical challenges can be presented in which the trainee must use the same anatomic and radiographic references required during actual surgical procedures. Using the aforementioned techniques, we have created simulators for ventriculostomy, percutaneous stereotactic lesion procedure for trigeminal neuralgia, and spinal instrumentation. The design and implementation of these platforms are presented. The system has provided the residents an opportunity to understand and appreciate the complex 3-dimensional anatomy of the 3 neurosurgical procedures simulated. The systems have also provided an opportunity to break procedures down into critical segments, allowing the user to concentrate on specific areas of deficiency.

Behavioral and anatomical consequences of repetitive mild thoracic spinal cord contusion injury in the rat.

PubMed

Jin, Ying; Bouyer, Julien; Haas, Christopher; Fischer, Itzhak

2014-07-01

Moderate and severe spinal cord contusion injuries have been extensively studied, yet much less is known about mild injuries. Mild contusions result in transient functional deficits, proceeding to near-complete recovery, but they may render the spinal cord vulnerable to future injuries. However, to date there have been no appropriate models to study the behavioral consequences, anatomical changes, and susceptibility of a mild contusion to repeated injuries, which may occur in children as well as adults during competitive sport activities. We have developed a novel mild spinal cord contusion injury model characterized by a sequence of transient functional deficits after the first injury and restoration to near-complete motor and sensory function, which is then followed up by a second injury. This model can serve not only to study the effects of repeated injuries on behavioral and anatomical changes, but also to examine the relationship between successive tissue damage and recovery of function. In the present study, we confirmed that mild thoracic spinal cord contusion, utilizing the NYU impactor device, resulted in localized tissue damage, characterized by a cystic cavity and peripheral rim of spared white matter at the injury epicenter, and rapid functional recovery to near-normal levels utilizing several behavioral tests. Repeated injury after 3weeks, when functional recovery has been completed, resulted in worsening of both motor and sensory function, which did not recover to prior levels. Anatomical analyses showed no differences in the volumes of spared white matter, lesion, or cyst, but revealed modest extension of lesion area rostral to the injury epicenter as well as an increase in inflammation and apoptosis. These studies demonstrate that a mild injury model can be used to test efficacy of treatments for repeated injuries and may serve to assist in the formulation of policies and clinical practice regarding mild SCI injury and spinal concussion. Copyright © 2014 Elsevier Inc. All rights reserved.

The Smn-Independent Beneficial Effects of Trichostatin A on an Intermediate Mouse Model of Spinal Muscular Atrophy

PubMed Central

Murray, Lyndsay M.; Beauvais, Ariane; Kothary, Rashmi

2014-01-01

Spinal muscular atrophy is an autosomal recessive neuromuscular disease characterized by the progressive loss of alpha motor neurons in the spinal cord. Trichostatin A (TSA) is a histone deacetylase inhibitor with beneficial effects in spinal muscular atrophy mouse models that carry the human SMN2 transgene. It is currently unclear whether TSA specifically targets the SMN2 gene or whether other genes respond to TSA and in turn provide neuroprotection in SMA mice. We have taken advantage of the Smn2B/- mouse model that does not harbor the human SMN2 transgene, to test the hypothesis that TSA has its beneficial effects through a non-SMN mediated pathway. TSA increased the median lifespan of Smn2B/- mice from twenty days to eight weeks. As well, there was a significant attenuation of weight loss and improved motor behavior. Pen test and righting reflex both showed significant improvement, and motor neurons in the spinal cord of Smn2B/- mice were protected from degeneration. Both the size and maturity of neuromuscular junctions were significantly improved in TSA treated Smn2B/- mice. Of interest, TSA treatment did not increase the levels of Smn protein in mouse embryonic fibroblasts or myoblasts obtained from the Smn2B/- mice. In addition, no change in the level of Smn transcripts or protein in the brain or spinal cord of TSA-treated SMA model mice was observed. Furthermore, TSA did not increase Smn protein levels in the hind limb muscle, heart, or liver of Smn2B/- mice. We therefore conclude that TSA likely exerts its effects independent of the endogenous mouse Smn gene. As such, identification of the pathways regulated by TSA in the Smn2B/- mice could lead to the development of novel therapeutics for treating SMA. PMID:24984019

[Finite element analysis of stress changes of posterior spinal pedicle screw infixation].

PubMed

Yan, Jia-Zhi; Wu, Zhi-Hong; Xu, Ri-Xin; Wang, Xue-Song; Xing, Ze-Jun; Zhao, Yu; Zhang, Jian-Guo; Shen, Jian-Xiong; Wang, Yi-Peng; Qiu, Gui-Xing

2009-01-06

To evaluate the mechanical response of L3-L4 segment after posterior interfixation with a transpedicle screw system. Spiral CT machine was used to conduct continuous parallel scan on the L3-L4 section of a 40-year-old healthy male Chinese. The image data thus obtained were introduced into MIMICS software to reconstruct the 2-D data into volume data and obtain 3-D models of every element.. Pro/3-D model construction software system was used to simulate the 3-D entity of L3-L4 fixed by screw robs through spinal pedicle via posterior approach that was introduced into the finite element software ABAQUS to construct a 3-D finite element model. The stress changes on the vertebrae and screw under the axial pressure of 0.5 mPa was analyzed. Under the evenly distributed pressure the displacement of the L4 model was 0.00125815 mm, with an error of only 0.8167% from the datum displacement. The convergence of the model was good. The stress of the fixed vertebral body, intervertebral disc, and internal fixators changed significantly. The stress concentration zone of the intervertebral disc turned from the posterolateral side to anterolateral side. The stress produced by the fixed vertebral bodies decreased significantly. Obvious stress concentration existed in the upper and lower sides of the base of screw and the fixed screw at the upper vertebral body bore greater stress than the lower vertebral body. Integration of computer aided device and finite element analysis can successfully stimulate the internal fixation of L3-IA visa posterior approach and observe the mechanic changes in the vertebral column more directly.

Local effect of zoledronic acid on new bone formation in posterolateral spinal fusion with demineralized bone matrix in a murine model.

PubMed

Zwolak, Pawel; Farei-Campagna, Jan; Jentzsch, Thorsten; von Rechenberg, Brigitte; Werner, Clément M

2018-01-01

Posterolateral spinal fusion is a common orthopaedic surgery performed to treat degenerative and traumatic deformities of the spinal column. In posteriolateral spinal fusion, different osteoinductive demineralized bone matrix products have been previously investigated. We evaluated the effect of locally applied zoledronic acid in combination with commercially available demineralized bone matrix putty on new bone formation in posterolateral spinal fusion in a murine in vivo model. A posterolateral sacral spine fusion in murine model was used to evaluate the new bone formation. We used the sacral spine fusion model to model the clinical situation in which a bone graft or demineralized bone matrix is applied after dorsal instrumentation of the spine. In our study, group 1 received decortications only (n = 10), group 2 received decortication, and absorbable collagen sponge carrier, group 3 received decortication and absorbable collagen sponge carrier with zoledronic acid in dose 10 µg, group 4 received demineralized bone matrix putty (DBM putty) plus decortication (n = 10), and group 5 received DBM putty, decortication and locally applied zoledronic acid in dose 10 µg. Imaging was performed using MicroCT for new bone formation assessment. Also, murine spines were harvested for histopathological analysis 10 weeks after surgery. The surgery performed through midline posterior approach was reproducible. In group with decortication alone there was no new bone formation. Application of demineralized bone matrix putty alone produced new bone formation which bridged the S1-S4 laminae. Local application of zoledronic acid to demineralized bone matrix putty resulted in significant increase of new bone formation as compared to demineralized bone matrix putty group alone. A single local application of zoledronic acid with DBM putty during posterolateral fusion in sacral murine spine model increased significantly new bone formation in situ in our model. Therefore, our results justify further investigations to potentially use local application of zoledronic acid in future clinical studies.

Modelling the endothelial blood-CNS barriers: a method for the production of robust in vitro models of the rat blood-brain barrier and blood-spinal cord barrier

PubMed Central

2013-01-01

Background Modelling the blood-CNS barriers of the brain and spinal cord in vitro continues to provide a considerable challenge for research studying the passage of large and small molecules in and out of the central nervous system, both within the context of basic biology and for pharmaceutical drug discovery. Although there has been considerable success over the previous two decades in establishing useful in vitro primary endothelial cell cultures from the blood-CNS barriers, no model fully mimics the high electrical resistance, low paracellular permeability and selective influx/efflux characteristics of the in vivo situation. Furthermore, such primary-derived cultures are typically labour-intensive and generate low yields of cells, limiting scope for experimental work. We thus aimed to establish protocols for the high yield isolation and culture of endothelial cells from both rat brain and spinal cord. Our aim was to optimise in vitro conditions for inducing phenotypic characteristics in these cells that were reminiscent of the in vivo situation, such that they developed into tight endothelial barriers suitable for performing investigative biology and permeability studies. Methods Brain and spinal cord tissue was taken from the same rats and used to specifically isolate endothelial cells to reconstitute as in vitro blood-CNS barrier models. Isolated endothelial cells were cultured to expand the cellular yield and then passaged onto cell culture inserts for further investigation. Cell culture conditions were optimised using commercially available reagents and the resulting barrier-forming endothelial monolayers were characterised by functional permeability experiments and in vitro phenotyping by immunocytochemistry and western blotting. Results Using a combination of modified handling techniques and cell culture conditions, we have established and optimised a protocol for the in vitro culture of brain and, for the first time in rat, spinal cord endothelial cells. High yields of both CNS endothelial cell types can be obtained, and these can be passaged onto large numbers of cell culture inserts for in vitro permeability studies. The passaged brain and spinal cord endothelial cells are pure and express endothelial markers, tight junction proteins and intracellular transport machinery. Further, both models exhibit tight, functional barrier characteristics that are discriminating against large and small molecules in permeability assays and show functional expression of the pharmaceutically important P-gp efflux transporter. Conclusions Our techniques allow the provision of high yields of robust sister cultures of endothelial cells that accurately model the blood-CNS barriers in vitro. These models are ideally suited for use in studying the biology of the blood-brain barrier and blood-spinal cord barrier in vitro and for pre-clinical drug discovery. PMID:23773766

Modelling the endothelial blood-CNS barriers: a method for the production of robust in vitro models of the rat blood-brain barrier and blood-spinal cord barrier.

PubMed

Watson, P Marc D; Paterson, Judy C; Thom, George; Ginman, Ulrika; Lundquist, Stefan; Webster, Carl I

2013-06-18

Modelling the blood-CNS barriers of the brain and spinal cord in vitro continues to provide a considerable challenge for research studying the passage of large and small molecules in and out of the central nervous system, both within the context of basic biology and for pharmaceutical drug discovery. Although there has been considerable success over the previous two decades in establishing useful in vitro primary endothelial cell cultures from the blood-CNS barriers, no model fully mimics the high electrical resistance, low paracellular permeability and selective influx/efflux characteristics of the in vivo situation. Furthermore, such primary-derived cultures are typically labour-intensive and generate low yields of cells, limiting scope for experimental work. We thus aimed to establish protocols for the high yield isolation and culture of endothelial cells from both rat brain and spinal cord. Our aim was to optimise in vitro conditions for inducing phenotypic characteristics in these cells that were reminiscent of the in vivo situation, such that they developed into tight endothelial barriers suitable for performing investigative biology and permeability studies. Brain and spinal cord tissue was taken from the same rats and used to specifically isolate endothelial cells to reconstitute as in vitro blood-CNS barrier models. Isolated endothelial cells were cultured to expand the cellular yield and then passaged onto cell culture inserts for further investigation. Cell culture conditions were optimised using commercially available reagents and the resulting barrier-forming endothelial monolayers were characterised by functional permeability experiments and in vitro phenotyping by immunocytochemistry and western blotting. Using a combination of modified handling techniques and cell culture conditions, we have established and optimised a protocol for the in vitro culture of brain and, for the first time in rat, spinal cord endothelial cells. High yields of both CNS endothelial cell types can be obtained, and these can be passaged onto large numbers of cell culture inserts for in vitro permeability studies. The passaged brain and spinal cord endothelial cells are pure and express endothelial markers, tight junction proteins and intracellular transport machinery. Further, both models exhibit tight, functional barrier characteristics that are discriminating against large and small molecules in permeability assays and show functional expression of the pharmaceutically important P-gp efflux transporter. Our techniques allow the provision of high yields of robust sister cultures of endothelial cells that accurately model the blood-CNS barriers in vitro. These models are ideally suited for use in studying the biology of the blood-brain barrier and blood-spinal cord barrier in vitro and for pre-clinical drug discovery.

Discrete mitochondrial aberrations in the spinal cord of sporadic ALS patients.

PubMed

Delic, Vedad; Kurien, Crupa; Cruz, Josean; Zivkovic, Sandra; Barretta, Jennifer; Thomson, Avery; Hennessey, Daniel; Joseph, Jaheem; Ehrhart, Jared; Willing, Alison E; Bradshaw, Patrick; Garbuzova-Davis, Svitlana

2018-08-01

Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease characterized by progressive motor neuron degeneration in the brain and spinal cord leading to muscle atrophy, paralysis, and death. Mitochondrial dysfunction is a major contributor to motor neuron degeneration associated with ALS progression. Mitochondrial abnormalities have been determined in spinal cords of animal disease models and ALS patients. However, molecular mechanisms leading to mitochondrial dysfunction in sporadic ALS (sALS) patients remain unclear. Also, segmental or regional variation in mitochondrial activity in the spinal cord has not been extensively examined in ALS. In our study, the activity of mitochondrial electron transport chain complex IV was examined in post-mortem gray and white matter of the cervical and lumbar spinal cords from male and female sALS patients and controls. Mitochondrial distribution and density in spinal cord motor neurons, lateral funiculus, and capillaries in gray and white matter were analyzed by immunohistochemistry. Results showed that complex IV activity was significantly decreased only in gray matter in both cervical and lumbar spinal cords from ALS patients. In ALS cervical and lumbar spinal cords, significantly increased mitochondrial density and altered distribution were observed in motor neurons, lateral funiculus, and cervical white matter capillaries. Discrete decreased complex IV activity in addition to changes in mitochondria distribution and density determined in the spinal cord in sALS patients are novel findings. These explicit mitochondrial defects in the spinal cord may contribute to ALS pathogenesis and should be considered in development of therapeutic approaches for this disease. © 2018 Wiley Periodicals, Inc.

Core Self-Evaluations as Personal Factors in the World Health Organization's International Classification of Functioning, Disability and Health Model: An Application in Persons with Spinal Cord Injury

ERIC Educational Resources Information Center

Yaghmanian, Rana; Smedema, Susan Miller; Thompson, Kerry

2017-01-01

Purpose: To evaluate Chan, Gelman, Ditchman, Kim, and Chiu's (2009) revised World Health Organization's International Classification of Functioning, Disability and Health (ICF) model using core self-evaluations (CSE) to account for Personal Factors in persons with spinal cord injury (SCI). Method: One hundred eighty-seven adults with SCI were…

Spinal Cord Injury Model Systems: Review of Program and National Database From 1970 to 2015.

PubMed

Chen, Yuying; DeVivo, Michael J; Richards, J Scott; SanAgustin, Theresa B

2016-10-01

The Spinal Cord Injury Model Systems (SCIMS) centers have provided continuous, comprehensive multidisciplinary care for persons with spinal cord injury (SCI) in the United States since their inception in 1970. In addition, the research conducted and the analysis of data collected at these centers facilitate advances in the care and the overall quality of life for people with SCI. Over the past 45 years, the SCIMS program and National Spinal Cord Injury Database (NSCID) have undergone major revisions, which must be recognized in the planning, conduct, and interpretation of SCIMS research to prevent misinterpretation of findings. Therefore, we provide herein a brief review of the SCIMS program and the associated NSCID throughout its history, emphasizing changes and accomplishments within the past 15 years, to facilitate a better understanding and interpretation of the data presented in SCIMS research publications, including the articles published in this special issue of the Archives. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Brain necrosis after fractionated radiation therapy: Is the halftime for repair longer than we thought?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bender, Edward T.

Purpose: To derive a radiobiological model that enables the estimation of brain necrosis and spinal cord myelopathy rates for a variety of fractionation schemes, and to compare repair effects between brain and spinal cord. Methods: Sigmoidal dose response relationships for brain radiation necrosis and spinal cord myelopathy are derived from clinical data using nonlinear regression. Three different repair models are considered and the repair halftimes are included as regression parameters. Results: For radiation necrosis, a repair halftime of 38.1 (range 6.9-76) h is found with monoexponential repair, while for spinal cord myelopathy, a repair halftime of 4.1 (range 0-8) hmore » is found. The best-fit alpha beta ratio is 0.96 (range 0.24-1.73)Conclusions: A radiobiological model that includes repair corrections can describe the clinical data for a variety of fraction sizes, fractionation schedules, and total doses. Modeling suggests a relatively long repair halftime for brain necrosis. This study suggests that the repair halftime for late radiation effects in the brain may be longer than is currently thought. If confirmed in future studies, this may lead to a re-evaluation of radiation fractionation schedules for some CNS diseases, particularly for those diseases where fractionated stereotactic radiation therapy is used.« less

Sitting biomechanics, part II: optimal car driver's seat and optimal driver's spinal model.

PubMed

Harrison, D D; Harrison, S O; Croft, A C; Harrison, D E; Troyanovich, S J

2000-01-01

Driving has been associated with signs and symptoms caused by vibrations. Sitting causes the pelvis to rotate backwards and the lumbar lordosis to reduce. Lumbar support and armrests reduce disc pressure and electromyographically recorded values. However, the ideal driver's seat and an optimal seated spinal model have not been described. To determine an optimal automobile seat and an ideal spinal model of a driver. Information was obtained from peer-reviewed scientific journals and texts, automotive engineering reports, and the National Library of Medicine. Driving predisposes vehicle operators to low-back pain and degeneration. The optimal seat would have an adjustable seat back incline of 100 degrees from horizontal, a changeable depth of seat back to front edge of seat bottom, adjustable height, an adjustable seat bottom incline, firm (dense) foam in the seat bottom cushion, horizontally and vertically adjustable lumbar support, adjustable bilateral arm rests, adjustable head restraint with lordosis pad, seat shock absorbers to dampen frequencies in the 1 to 20 Hz range, and linear front-back travel of the seat enabling drivers of all sizes to reach the pedals. The lumbar support should be pulsating in depth to reduce static load. The seat back should be damped to reduce rebounding of the torso in rear-end impacts. The optimal driver's spinal model would be the average Harrison model in a 10 degrees posterior inclining seat back angle.

Parametric convergence sensitivity and validation of a finite element model of the human lumbar spine.

PubMed

Ayturk, Ugur M; Puttlitz, Christian M

2011-08-01

The primary objective of this study was to generate a finite element model of the human lumbar spine (L1-L5), verify mesh convergence for each tissue constituent and perform an extensive validation using both kinematic/kinetic and stress/strain data. Mesh refinement was accomplished via convergence of strain energy density (SED) predictions for each spinal tissue. The converged model was validated based on range of motion, intradiscal pressure, facet force transmission, anterolateral cortical bone strain and anterior longitudinal ligament deformation predictions. Changes in mesh resolution had the biggest impact on SED predictions under axial rotation loading. Nonlinearity of the moment-rotation curves was accurately simulated and the model predictions on the aforementioned parameters were in good agreement with experimental data. The validated and converged model will be utilised to study the effects of degeneration on the lumbar spine biomechanics, as well as to investigate the mechanical underpinning of the contemporary treatment strategies.

Spinal Changes of a Newly Isolated Neuropeptide Endomorphin-2 Concomitant with Vincristine-Induced Allodynia

PubMed Central

Huang, Ben-Qing; Liu, Ji-Dong; Liu, Hui; Zhang, Nan; Li, Li; Chen, Jian-Hua

2014-01-01

Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain unclear. There is increasing evidence implicating the involvement of spinal endomorphin-2 (EM2) in neuropathic pain. In this study, we used a vincristine-evoked rat CNP model displaying mechanical allodynia and central sensitization, and observed a significant decrease in the expression of spinal EM2 in CNP. Also, while intrathecal administration of exogenous EM2 attenuated allodynia and central sensitization, the mu-opioid receptor antagonist β-funaltrexamine facilitated these events. We found that the reduction in spinal EM2 was mediated by increased activity of dipeptidylpeptidase IV, possibly as a consequence of chemotherapy-induced oxidative stress. Taken together, our findings suggest that a decrease in spinal EM2 expression causes the loss of endogenous analgesia and leads to enhanced pain sensation in CNP. PMID:24586889

Clinical interpretation of the Spinal Cord Injury Functional Index (SCI-FI).

PubMed

Fyffe, Denise; Kalpakjian, Claire Z; Slavin, Mary; Kisala, Pamela; Ni, Pengsheng; Kirshblum, Steven C; Tulsky, David S; Jette, Alan M

2016-09-01

To provide validation of functional ability levels for the Spinal Cord Injury - Functional Index (SCI-FI). Cross-sectional. Inpatient rehabilitation hospital and community settings. A sample of 855 individuals with traumatic spinal cord injury enrolled in 6 rehabilitation centers participating in the National Spinal Cord Injury Model Systems Network. Not Applicable. Spinal Cord Injury-Functional Index (SCI-FI). Cluster analyses identified three distinct groups that represent low, mid-range and high SCI-FI functional ability levels. Comparison of clusters on personal and other injury characteristics suggested some significant differences between groups. These results strongly support the use of SCI-FI functional ability levels to document the perceived functional abilities of persons with SCI. Results of the cluster analysis suggest that the SCI-FI functional ability levels capture function by injury characteristics. Clinical implications regarding tracking functional activity trajectories during follow-up visits are discussed.

Transmitters and pathways mediating inhibition of spinal itch-signaling neurons by scratching and other counterstimuli.

PubMed

Akiyama, Tasuku; Iodi Carstens, Mirela; Carstens, Earl

2011-01-01

Scratching relieves itch, but the underlying neural mechanisms are poorly understood. We presently investigated a role for the inhibitory neurotransmitters GABA and glycine in scratch-evoked inhibition of spinal itch-signaling neurons in a mouse model of chronic dry skin itch. Superficial dorsal horn neurons ipsilateral to hindpaw dry skin treatment exhibited a high level of spontaneous firing that was significantly attenuated by cutaneous scratching, pinch and noxious heat. Scratch-evoked inhibition was nearly abolished by spinal delivery of the glycine antagonist, strychnine, and was markedly attenuated by respective GABA(A) and GABA(B) antagonists bicuculline and saclofen. Scratch-evoked inhibition was also significantly attenuated (but not abolished) by interruption of the upper cervical spinal cord, indicating the involvement of both segmental and suprasegmental circuits that engage glycine- and GABA-mediated inhibition of spinal itch-signaling neurons by noxious counterstimuli.

Osthole attenuates spinal cord ischemia-reperfusion injury through mitochondrial biogenesis-independent inhibition of mitochondrial dysfunction in rats.

PubMed

Zhou, Yue-fei; Li, Liang; Feng, Feng; Yuan, Hua; Gao, Da-kuan; Fu, Luo-an; Fei, Zhou

2013-12-01

Osthole, the main bioactive compounds isolated from the traditional Chinese medical herb broad Cnidium monnieri (L.) cusson, has been shown to exert spectrum of pharmacologic activities. The aim of this study was to investigate the potential neuroprotective effects of osthole against spinal cord ischemia-reperfusion injury in rats. Osthole was administrated at the concentration of 0.1, 1, 10, 50, or 200 mg/kg (intraperitoneally) 1 h before spinal cord ischemia. The effects on spinal cord injury were measured by spinal cord water content, infarct volume, hematoxylin and eosin staining, and neurologic assessment. Mitochondria were purified from injured spinal cord tissue to determine mitochondrial function. We found that treatment with osthole (10 and 50 mg/kg) significantly decreased spinal cord water content and infarct volume, preserved normal motor neurons, and improved neurologic functions. These protective effects can be also observed even if the treatment was delayed to 4 h after reperfusion. Osthole treatment preserved mitochondrial membrane potential level, reduced reactive oxygen species production, increased adenosine triphosphate generation, and inhibited cytochrome c release in mitochondrial samples. Moreover, osthole increased mitochondria respiratory chain complex activities in spinal cord tissue, with no effect on mitochondrial DNA content and the expression of mitochondrial-specific transcription factors. All these findings demonstrate the neuroprotective effect of osthole in spinal cord ischemia-reperfusion injury model and suggest that oshtole-induced neuroprotection was mediated by mitochondrial biogenesis-independent inhibition of mitochondrial dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.

Shock Wave Treatment Protects From Neuronal Degeneration via a Toll-Like Receptor 3 Dependent Mechanism: Implications of a First-Ever Causal Treatment for Ischemic Spinal Cord Injury.

PubMed

Lobenwein, Daniela; Tepeköylü, Can; Kozaryn, Radoslaw; Pechriggl, Elisabeth J; Bitsche, Mario; Graber, Michael; Fritsch, Helga; Semsroth, Severin; Stefanova, Nadia; Paulus, Patrick; Czerny, Martin; Grimm, Michael; Holfeld, Johannes

2015-10-27

Paraplegia following spinal cord ischemia represents a devastating complication of both aortic surgery and endovascular aortic repair. Shock wave treatment was shown to induce angiogenesis and regeneration in ischemic tissue by modulation of early inflammatory response via Toll-like receptor (TLR) 3 signaling. In preclinical and clinical studies, shock wave treatment had a favorable effect on ischemic myocardium. We hypothesized that shock wave treatment also may have a beneficial effect on spinal cord ischemia. A spinal cord ischemia model in mice and spinal slice cultures ex vivo were performed. Treatment groups received immediate shock wave therapy, which resulted in decreased neuronal degeneration and improved motor function. In spinal slice cultures, the activation of TLR3 could be observed. Shock wave effects were abolished in spinal slice cultures from TLR3(-/-) mice, whereas the effect was still present in TLR4(-/-) mice. TLR4 protein was found to be downregulated parallel to TLR3 signaling. Shock wave-treated animals showed significantly better functional outcome and survival. The protective effect on neurons could be reproduced in human spinal slices. Shock wave treatment protects from neuronal degeneration via TLR3 signaling and subsequent TLR4 downregulation. Consequently, it represents a promising treatment option for the devastating complication of spinal cord ischemia after aortic repair. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Effects of vertebral column distraction on transcranial electrical stimulation-motor evoked potential and histology of the spinal cord in a porcine model.

PubMed

Yang, Jae Hyuk; Suh, Seung Woo; Modi, Hitesh N; Ramani, Easwar T; Hong, Jae Young; Hwang, Jin Ho; Jung, Woon Yong

2013-05-01

Spinal cord injury can occur following surgical procedures for correction of scoliosis and kyphosis, as these procedures produce lengthening of the vertebral column. The objective of this study was to cause spinal cord injury by vertebral column distraction and evaluate the histological changes in the spinal cord in relationship to the pattern of recovery from the spinal cord injury. Global osteotomy of all three spinal columns was performed on the ninth thoracic vertebra of sixteen pigs. The osteotomized vertebra was distracted until transcranial electrical stimulation-motor evoked potential (TES-MEP) signals disappeared or decreased by >80% compared with the baseline amplitude; this was defined as spinal cord injury. The distraction distance at which spinal cord injury occurred was measured, the distraction was released, and the TES-MEP recovery pattern was observed. A wake-up test was performed, two days of observations were made, and histological changes were evaluated in relationship to the recovery pattern. Spinal cord injury developed at a distraction distance of 20.2 ± 4.7 mm, equivalent to 3.6% of the thoracolumbar spinal length, and the distraction distance was correlated with the thoracolumbar spinal length (r = 0.632, p = 0.009). No animals exhibited complete recovery according to TES-MEP testing, eleven exhibited incomplete recovery, and five exhibited no recovery. During the two days of observation, all eleven animals with incomplete recovery showed positive responses to sensory and motor tests, whereas none of the five animals with no recovery had positive responses. On histological evaluation, three animals that exhibited no recovery all showed complete severance of nerve fibers (axotomy), whereas six animals that exhibited incomplete recovery all showed partial white-matter injury. Parallel distraction of approximately 3.6% of the thoracolumbar length after global osteotomy resulted in spinal cord injury and histological evidence of spinal cord damage. The pattern of recovery from the spinal cord injury after release of the distraction was consistent with the degree of axonal damage. Axotomy was observed in animals that exhibited no recovery on TES-MEP, and only hemorrhagic changes in the white matter were observed in animals that exhibited incomplete recovery.

Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat

PubMed Central

Sagar, D.R.; Nwosu, L.; Walsh, D.A.; Chapman, V.

2015-01-01

Summary Objective Although analgesic approaches targeting nerve growth factor (NGF) for the treatment of osteoarthritis (OA) pain remain of clinical interest, neurophysiological mechanisms by which NGF contribute to OA pain remain unclear. We investigated the impact of local elevation of knee joint NGF on knee joint, vs remote (hindpaw), evoked responses of spinal neurones in a rodent model of OA pain. Design In vivo spinal electrophysiology was carried out in anaesthetised rats with established pain behaviour and joint pathology following intra-articular injection of monosodium iodoacetate (MIA), vs injection of saline. Neuronal responses to knee joint extension and flexion, mechanical punctate stimulation of the peripheral receptive fields over the knee and at a remote site (ipsilateral hind paw) were studied before, and following, intra-articular injection of NGF (10 μg/50 μl) or saline. Results MIA-injected rats exhibited significant local (knee joint) and remote (lowered hindpaw withdrawal thresholds) changes in pain behaviour, and joint pathology. Intra-articular injection of NGF significantly (P < 0.05) increased knee extension-evoked firing of spinal neurones and the size of the peripheral receptive fields of spinal neurones (100% increase) over the knee joint in MIA rats, compared to controls. Intra-articular NGF injection did not significantly alter responses of spinal neurones following noxious stimulation of the ipsilateral hind paw in MIA-injected rats. Conclusion The facilitatory effects of intra-articular injection of NGF on spinal neurones receiving input from the knee joint provide a mechanistic basis for NGF mediated augmentation of OA knee pain, however additional mechanisms may contribute to the spread of pain to remote sites. PMID:25623624

Prevalence and factors associated with a higher risk of neck and back pain among permanent wheelchair users: a cross-sectional study.

PubMed

Kovacs, Francisco M; Seco, Jesús; Royuela, Ana; Barriga, Andrés; Zamora, Javier

2018-04-01

Cross-sectional study. To determine the prevalence of, and factors associated with, spinal pain among wheelchair users. Four Spanish hospitals specialized in providing care for wheelchair users. Persons who had used a wheelchair for a median (IRQ) of 10 (5;19) years, 27% of them due to reasons other than spinal cord injury, were recruited consecutively (n = 750). Data on 43 demographic, psychosocial, ergonomic, and clinical variables were collected, and analyzed. Main outcome measures were: point prevalence of neck (NP), thoracic (TP), low back pain (LBP), and pain at any spinal level (PASL); and factors associated with them. Point prevalence was 56% for NP, 54% for TP, 45% for LBP, and 76% for PSAL. PASL was associated with a lower quality of life (OR (95% CI) 0.91 (0.86; 0.97)). Multivariable regression models showed that the main factors associated with significant pain (≥1.5 VAS points) were: (a) For NP: cervical spinal injury and wheelchair seat cushion thickness, (b) For TP: thoracic spinal injury and sagittal index, (c) For LBP: thoracic or lumbar spinal injury, with some sensitivity remaining, (d) For PASL: being female, living alone, and using a non-power wheelchair. Discrimination (AUC) of these models ranged between 0.638 and 0.818. p-values in the Hosmer-Lemeshow test ranged between 0.420 and 0.701. Prevalence of spinal pain among wheelchair users is high. It is associated with a lower quality of life. Future studies should assess whether using a power wheelchair affects PASL, and if the thickness of seat cushion affects NP. Spanish Back Pain Research Network.

Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat.

PubMed

Sagar, D R; Nwosu, L; Walsh, D A; Chapman, V

2015-06-01

Although analgesic approaches targeting nerve growth factor (NGF) for the treatment of osteoarthritis (OA) pain remain of clinical interest, neurophysiological mechanisms by which NGF contribute to OA pain remain unclear. We investigated the impact of local elevation of knee joint NGF on knee joint, vs remote (hindpaw), evoked responses of spinal neurones in a rodent model of OA pain. In vivo spinal electrophysiology was carried out in anaesthetised rats with established pain behaviour and joint pathology following intra-articular injection of monosodium iodoacetate (MIA), vs injection of saline. Neuronal responses to knee joint extension and flexion, mechanical punctate stimulation of the peripheral receptive fields over the knee and at a remote site (ipsilateral hind paw) were studied before, and following, intra-articular injection of NGF (10 μg/50 μl) or saline. MIA-injected rats exhibited significant local (knee joint) and remote (lowered hindpaw withdrawal thresholds) changes in pain behaviour, and joint pathology. Intra-articular injection of NGF significantly (P < 0.05) increased knee extension-evoked firing of spinal neurones and the size of the peripheral receptive fields of spinal neurones (100% increase) over the knee joint in MIA rats, compared to controls. Intra-articular NGF injection did not significantly alter responses of spinal neurones following noxious stimulation of the ipsilateral hind paw in MIA-injected rats. The facilitatory effects of intra-articular injection of NGF on spinal neurones receiving input from the knee joint provide a mechanistic basis for NGF mediated augmentation of OA knee pain, however additional mechanisms may contribute to the spread of pain to remote sites. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Electrophysiological characterization of spinal neurons in different models of diabetes type 1- and type 2-induced neuropathy in rats.

PubMed

Schuelert, N; Gorodetskaya, N; Just, S; Doods, H; Corradini, L

2015-04-16

Diabetic polyneuropathy (DPN) is a devastating complication of diabetes. The underlying pathogenesis of DPN is still elusive and an effective treatment devoid of side effects presents a challenge. There is evidence that in type-1 and -2 diabetes, metabolic and morphological changes lead to peripheral nerve damage and altered central nociceptive transmission, which may contribute to neuropathic pain symptoms. We characterized the electrophysiological response properties of spinal wide dynamic range (WDR) neurons in three diabetic models. The streptozotocin (STZ) model was used as a drug-induced model of type-1 diabetes, and the BioBreeding/Worcester (BB/Wor) and Zucker diabetic fatty (ZDF) rat models were used for genetic DPN models. Data were compared to the respective control group (BB/Wor diabetic-resistant, Zucker lean (ZL) and saline-injected Wistar rat). Response properties of WDR neurons to mechanical stimulation and spontaneous activity were assessed. We found abnormal response properties of spinal WDR neurons in all diabetic rats but not controls. Profound differences between models were observed. In BB/Wor diabetic rats evoked responses were increased, while in ZDF rats spontaneous activity was increased and in STZ rats mainly after discharges were increased. The abnormal response properties of neurons might indicate differential pathological, diabetes-induced, changes in spinal neuronal transmission. This study shows for the first time that specific electrophysiological response properties are characteristic for certain models of DPN and that these might reflect the diverse and complex symptomatology of DPN in the clinic. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Suprapubic Bladder Catheterization of Male Spinal-Cord–Injured Sprague–Dawley Rats

PubMed Central

Robinson, Mary A; Herron, Alan J; Goodwin, Bradford S; Grill, Raymond J

2012-01-01

The rat spinal-cord–injury (SCI) model is widely used to study the pathologic mechanisms that contribute to sensory and motor dysfunction in humans. This model is thought to mimic many of the negative outcomes experienced by humans after spinal contusion injury. We theorized that manual bladder expression contributed to the kidney and bladder lesions reported in previous studies using the rat SCI model. In the present study, rats were surgically implanted with bladder catheters after spinal contusion injury to provide continuous drainage of urine. After 72 h, the rats were euthanized and their kidneys and bladders examined histologically. BUN, serum creatinine, and urine protein were compared at 0 and 72 h after surgery. Kidney and bladder lesions were similar in SCI rats with and without implanted bladder catheters. BUN at 72 h was higher than baseline values in both groups, whereas serum creatinine was higher at 72 h compared with baseline values only in the catheterized rats. These findings indicate that suprapubic bladder catheterization does not reduce hydronephrosis in SCI rats and that the standard of care for bladder evacuation should continue to be manual expression of urine. PMID:22330872

Biomechanical consequences of running with deep core muscle weakness.

PubMed

Raabe, Margaret E; Chaudhari, Ajit M W

2018-01-23

The deep core muscles are often neglected or improperly trained in athletes. Improper function of this musculature may lead to abnormal spinal loading, muscle strain, or injury to spinal structures, all of which have been associated with increased low back pain (LBP) risk. The purpose of this study was to identify potential strategies used to compensate for weakness of the deep core musculature during running and to identify accompanying changes in compressive and shear spinal loads. Kinematically-driven simulations of overground running were created for eight healthy young adults in OpenSim at increasing levels of deep core muscle weakness. The deep core muscles (multifidus, quadratus lumborum, psoas, and deep fascicles of the erector spinae) were weakened individually and together. The superficial longissimus thoracis was a significant compensator for 4 out of 5 weakness conditions (p < 0.05). The deep erector spinae required the largest compensations when weakened individually (up to a 45 ± 10% increase in compensating muscle force production, p = 0.004), revealing it may contribute most to controlling running kinematics. With complete deep core muscle weakness, peak anterior shear loading increased on all lumbar vertebrae (up to 19%, p = 0.001). Additionally, compressive spinal loading increased on the upper lumbar vertebrae (up to 15%, p = 0.007) and decreased on the lower lumbar vertebrae (up to 8%, p = 0.008). Muscular compensations may increase risk of muscular fatigue or injury and increased spinal loading over numerous gait cycles may result in damage to spinal structures. Therefore, insufficient strength of the deep core musculature may increase a runner's risk of developing LBP. Copyright © 2017 Elsevier Ltd. All rights reserved.

Axon and dendrite geography predict the specificity of synaptic connections in a functioning spinal cord network.

PubMed

Li, Wen-Chang; Cooke, Tom; Sautois, Bart; Soffe, Stephen R; Borisyuk, Roman; Roberts, Alan

2007-09-10

How specific are the synaptic connections formed as neuronal networks develop and can simple rules account for the formation of functioning circuits? These questions are assessed in the spinal circuits controlling swimming in hatchling frog tadpoles. This is possible because detailed information is now available on the identity and synaptic connections of the main types of neuron. The probabilities of synapses between 7 types of identified spinal neuron were measured directly by making electrical recordings from 500 pairs of neurons. For the same neuron types, the dorso-ventral distributions of axons and dendrites were measured and then used to calculate the probabilities that axons would encounter particular dendrites and so potentially form synaptic connections. Surprisingly, synapses were found between all types of neuron but contact probabilities could be predicted simply by the anatomical overlap of their axons and dendrites. These results suggested that synapse formation may not require axons to recognise specific, correct dendrites. To test the plausibility of simpler hypotheses, we first made computational models that were able to generate longitudinal axon growth paths and reproduce the axon distribution patterns and synaptic contact probabilities found in the spinal cord. To test if probabilistic rules could produce functioning spinal networks, we then made realistic computational models of spinal cord neurons, giving them established cell-specific properties and connecting them into networks using the contact probabilities we had determined. A majority of these networks produced robust swimming activity. Simple factors such as morphogen gradients controlling dorso-ventral soma, dendrite and axon positions may sufficiently constrain the synaptic connections made between different types of neuron as the spinal cord first develops and allow functional networks to form. Our analysis implies that detailed cellular recognition between spinal neuron types may not be necessary for the reliable formation of functional networks to generate early behaviour like swimming.

Influence of Tanshinone IIa on heat shock protein 70, Bcl-2 and Bax expression in rats with spinal ischemia/reperfusion injury.

PubMed

Zhang, Li; Gan, Weidong; An, Guoyao

2012-12-25

Tanshinone IIa is an effective monomer component of Danshen, which is a traditional Chinese medicine for activating blood circulation to dissipate blood stasis. Tanshinone IIa can effectively improve brain tissue ischemia/hypoxia injury. The present study established a rat model of spinal cord ischemia/reperfusion injury and intraperitoneally injected Tanshinone IIa, 0.5 hour prior to model establishment. Results showed that Tanshinone IIa promoted heat shock protein 70 and Bcl-2 protein expression, but inhibited Bax protein expression in the injured spinal cord after ischemia/reperfusion injury. Furthermore, Nissl staining indicated a reduction in nerve cell apoptosis and fewer pathological lesions in the presence of Tanshinone IIa, compared with positive control Danshen injection.

Development of a Personalized Model for Pressure Ulcer Prevention Acutely Following Spinal Cord Injury: Biomarkers of Muscle Composition and Resilience

DTIC Science & Technology

2016-10-01

SUBJECT TERMS Spinal cord injury, pressure ulcer prevention, biomarkers, personalized healthcare 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...ulcer prevention, biomarkers, personalized healthcare 3. Accomplishments Major Project Goals Task 1: Subject Recruitment and Data Collection

Estimating the global incidence of traumatic spinal cord injury.

PubMed

Fitzharris, M; Cripps, R A; Lee, B B

2014-02-01

Population modelling--forecasting. To estimate the global incidence of traumatic spinal cord injury (TSCI). An initiative of the International Spinal Cord Society (ISCoS) Prevention Committee. Regression techniques were used to derive regional and global estimates of TSCI incidence. Using the findings of 31 published studies, a regression model was fitted using a known number of TSCI cases as the dependent variable and the population at risk as the single independent variable. In the process of deriving TSCI incidence, an alternative TSCI model was specified in an attempt to arrive at an optimal way of estimating the global incidence of TSCI. The global incidence of TSCI was estimated to be 23 cases per 1,000,000 persons in 2007 (179,312 cases per annum). World Health Organization's regional results are provided. Understanding the incidence of TSCI is important for health service planning and for the determination of injury prevention priorities. In the absence of high-quality epidemiological studies of TSCI in each country, the estimation of TSCI obtained through population modelling can be used to overcome known deficits in global spinal cord injury (SCI) data. The incidence of TSCI is context specific, and an alternative regression model demonstrated how TSCI incidence estimates could be improved with additional data. The results highlight the need for data standardisation and comprehensive reporting of national level TSCI data. A step-wise approach from the collation of conventional epidemiological data through to population modelling is suggested.

Inflammatory cascades mediate synapse elimination in spinal cord compression

PubMed Central

2014-01-01

Background Cervical compressive myelopathy (CCM) is caused by chronic spinal cord compression due to spondylosis, a degenerative disc disease, and ossification of the ligaments. Tip-toe walking Yoshimura (twy) mice are reported to be an ideal animal model for CCM-related neuronal dysfunction, because they develop spontaneous spinal cord compression without any artificial manipulation. Previous histological studies showed that neurons are lost due to apoptosis in CCM, but the mechanism underlying this neurodegeneration was not fully elucidated. The purpose of this study was to investigate the pathophysiology of CCM by evaluating the global gene expression of the compressed spinal cord and comparing the transcriptome analysis with the physical and histological findings in twy mice. Methods Twenty-week-old twy mice were divided into two groups according to the magnetic resonance imaging (MRI) findings: a severe compression (S) group and a mild compression (M) group. The transcriptome was analyzed by microarray and RT-PCR. The cellular pathophysiology was examined by immunohistological analysis and immuno-electron microscopy. Motor function was assessed by Rotarod treadmill latency and stride-length tests. Results Severe cervical calcification caused spinal canal stenosis and low functional capacity in twy mice. The microarray analysis revealed 215 genes that showed significantly different expression levels between the S and the M groups. Pathway analysis revealed that genes expressed at higher levels in the S group were enriched for terms related to the regulation of inflammation in the compressed spinal cord. M1 macrophage-dominant inflammation was present in the S group, and cysteine-rich protein 61 (Cyr61), an inducer of M1 macrophages, was markedly upregulated in these spinal cords. Furthermore, C1q, which initiates the classical complement cascade, was more upregulated in the S group than in the M group. The confocal and electron microscopy observations indicated that classically activated microglia/macrophages had migrated to the compressed spinal cord and eliminated synaptic terminals. Conclusions We revealed the detailed pathophysiology of the inflammatory response in an animal model of chronic spinal cord compression. Our findings suggest that complement-mediated synapse elimination is a central mechanism underlying the neurodegeneration in CCM. PMID:24589419

Bimodal Modulation of Ipsilateral Spinal-Coeruleo-Spinal Pathway in CRPS: A Novel Model for Explaining Different Clinical Features of the Syndrome.

PubMed

Carcamo, Cesar R

2015-08-01

The objective is to present a hypothesis to explain the sensory, autonomic, and motor disturbances associated with complex regional pain syndrome (CRPS) syndrome. The author reviewed the available and relevant literature, which was supplemented with research on experimental animal models, with a focus on how they may translate into humans, particularly in areas about pathophysiologic mechanisms of CRPS. We propose that different CRPS subtypes may result from facilitative or inhibitory influences exerted by the spinal-coeruleo-spinal pathway in three sites at the spinal cord: the dorsal horn (DH), intermediolateral cell column (IML) and ventral horn (VH). A facilitatory influence over DH may have a pronociceptive effect that explains exacerbated pain, sensory disturbances, and spreading sensitization and neuroinflammation. Conversely, a facilitatory influence over preganglionic neurons located in IML cell column may increase sympathetic outflow with peripheral vasoconstriction, which leads to cold skin, ipsilateral limb ischaemia, and sympathetically maintained pain (SMP). For patients presenting with these symptoms, a descending inhibitory influence would be predicted to result in decreased sympathetic outflow and warm skin, as well as impairment of peripheral vasoconstrictor reflexes. Finally, a descending inhibitory influence over VH could explain muscle weakness and decreased active range of motion, while also facilitating motor reflexes, tremor and dystonia. The proposed model provides a mechanistically based diagnostic scheme for classifying and explaining the sensory, autonomic and motor disturbances associated with CRPS syndrome. Wiley Periodicals, Inc.

Intraperitoneal injection of thalidomide attenuates bone cancer pain and decreases spinal tumor necrosis factor-α expression in a mouse model.

PubMed

Gu, Xiaoping; Zheng, Yaguo; Ren, Bingxu; Zhang, Rui; Mei, Fengmei; Zhang, Juan; Ma, Zhengliang

2010-10-05

Tumor necrosis factor α (TNF-α) may have a pivotal role in the genesis of mechanical allodynia and thermal hyperalgesia during inflammatory and neuropathic pain. Thalidomide has been shown to selectively inhibit TNF-α production. Previous studies have suggested that thalidomide exerts anti-nociceptive effects in various pain models, but its effects on bone cancer pain have not previously been studied. Therefore, in the present study, we investigated the effect of thalidomide on bone cancer-induced hyperalgesia and up-regulated expression of spinal TNF-α in a mouse model. Osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce ongoing bone cancer related pain behaviors. At day 5, 7, 10 and 14 after operation, the expression of TNF-α in the spinal cord was higher in tumor-bearing mice compared to the sham mice. Intraperitoneal injection of thalidomide (50 mg/kg), started at day 1 after surgery and once daily thereafter until day 7, attenuated bone cancer-evoked mechanical allodynia and thermal hyperalgesia as well as the up-regulation of TNF-α in the spinal cord. These results suggest that thalidomide can efficiently alleviate bone cancer pain and it may be a useful alternative or adjunct therapy for bone cancer pain. Our data also suggest a role of spinal TNF-α in the development of bone cancer pain.

Intraperitoneal injection of thalidomide attenuates bone cancer pain and decreases spinal tumor necrosis factor-α expression in a mouse model

PubMed Central

2010-01-01

Background Tumor necrosis factor α (TNF-α) may have a pivotal role in the genesis of mechanical allodynia and thermal hyperalgesia during inflammatory and neuropathic pain. Thalidomide has been shown to selectively inhibit TNF-α production. Previous studies have suggested that thalidomide exerts anti-nociceptive effects in various pain models, but its effects on bone cancer pain have not previously been studied. Therefore, in the present study, we investigated the effect of thalidomide on bone cancer-induced hyperalgesia and up-regulated expression of spinal TNF-α in a mouse model. Results Osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce ongoing bone cancer related pain behaviors. At day 5, 7, 10 and 14 after operation, the expression of TNF-α in the spinal cord was higher in tumor-bearing mice compared to the sham mice. Intraperitoneal injection of thalidomide (50 mg/kg), started at day 1 after surgery and once daily thereafter until day 7, attenuated bone cancer-evoked mechanical allodynia and thermal hyperalgesia as well as the up-regulation of TNF-α in the spinal cord. Conclusions These results suggest that thalidomide can efficiently alleviate bone cancer pain and it may be a useful alternative or adjunct therapy for bone cancer pain. Our data also suggest a role of spinal TNF-α in the development of bone cancer pain. PMID:20923560

The PPAR alpha agonist gemfibrozil is an ineffective treatment for spinal cord injured mice.

PubMed

Almad, Akshata; Lash, A Todd; Wei, Ping; Lovett-Racke, Amy E; McTigue, Dana M

2011-12-01

Peroxisome Proliferator Activated Receptor (PPAR)-α is a key regulator of lipid metabolism and recent studies reveal it also regulates inflammation in several different disease models. Gemfibrozil, an agonist of PPAR-α, is a FDA approved drug for hyperlipidemia and has been shown to inhibit clinical signs in a rodent model of multiple sclerosis. Since many studies have shown improved outcome from spinal cord injury (SCI) by anti-inflammatory and neuroprotective agents, we tested the efficacy of oral gemfibrozil given before or after SCI for promoting tissue preservation and behavioral recovery after spinal contusion injury in mice. Unfortunately, the results were contrary to our hypothesis; in our first attempt, gemfibrozil treatment exacerbated locomotor deficits and increased tissue pathology after SCI. In subsequent experiments, the behavioral effects were not replicated but histological outcomes again were worse. We also tested the efficacy of a different PPAR-α agonist, fenofibrate, which also modulates immune responses and is beneficial in several neurodegenerative disease models. Fenofibrate treatment did not improve recovery, although there was a slight trend for a modest increase in histological tissue sparing. Based on our results, we conclude that PPAR-α agonists yield either no effect or worsen recovery from spinal cord injury, at least at the doses and the time points of drug delivery tested here. Further, patients sustaining spinal cord injury while taking gemfibrozil might be prone to exacerbated tissue damage. Copyright © 2011 Elsevier Inc. All rights reserved.

Computational Modeling of Space Physiology for Informing Spaceflight Countermeasure Design and Predictions of Efficacy

NASA Technical Reports Server (NTRS)

Lewandowski, B. E.; DeWitt, J. K.; Gallo, C. A.; Gilkey, K. M.; Godfrey, A. P.; Humphreys, B. T.; Jagodnik, K. M.; Kassemi, M.; Myers, J. G.; Nelson, E. S.;

Design-Based Comparison of Spine Surgery Simulators: Optimizing Educational Features of Surgical Simulators.

PubMed

Ryu, Won Hyung A; Mostafa, Ahmed E; Dharampal, Navjit; Sharlin, Ehud; Kopp, Gail; Jacobs, W Bradley; Hurlbert, R John; Chan, Sonny; Sutherland, Garnette R

2017-10-01

Simulation-based education has made its entry into surgical residency training, particularly as an adjunct to hands-on clinical experience. However, one of the ongoing challenges to wide adoption is the capacity of simulators to incorporate educational features required for effective learning. The aim of this study was to identify strengths and limitations of spine simulators to characterize design elements that are essential in enhancing resident education. We performed a mixed qualitative and quantitative cohort study with a focused survey and interviews of stakeholders in spine surgery pertaining to their experiences on 3 spine simulators. Ten participants were recruited spanning all levels of training and expertise until qualitative analysis reached saturation of themes. Participants were asked to perform lumbar pedicle screw insertion on 3 simulators. Afterward, a 10-item survey was administrated and a focused interview was conducted to explore topics pertaining to the design features of the simulators. Overall impressions of the simulators were positive with regards to their educational benefit, but our qualitative analysis revealed differing strengths and limitations. Main design strengths of the computer-based simulators were incorporation of procedural guidance and provision of performance feedback. The synthetic model excelled in achieving more realistic haptic feedback and incorporating use of actual surgical tools. Stakeholders from trainees to experts acknowledge the growing role of simulation-based education in spine surgery. However, different simulation modalities have varying design elements that augment learning in distinct ways. Characterization of these design characteristics will allow for standardization of simulation curricula in spinal surgery, optimizing educational benefit. Copyright © 2017 Elsevier Inc. All rights reserved.

A Novel Spinal Implant for Fusionless Scoliosis Correction: A Biomechanical Analysis of the Motion Preserving Properties of a Posterior Periapical Concave Distraction Device.

PubMed

Holewijn, Roderick M; de Kleuver, Marinus; van der Veen, Albert J; Emanuel, Kaj S; Bisschop, Arno; Stadhouder, Agnita; van Royen, Barend J; Kingma, Idsart

2017-08-01

Biomechanical study. Recently, a posterior concave periapical distraction device for fusionless scoliosis correction was introduced. The goal of this study was to quantify the effect of the periapical distraction device on spinal range of motion (ROM) in comparison with traditional rigid pedicle screw-rod instrumentation. Using a spinal motion simulator, 6 human spines were loaded with 4 N m and 6 porcine spines with 2 N m to induce flexion-extension (FE), lateral bending (LB), and axial rotation (AR). ROM was measured in 3 conditions: untreated, periapical distraction device, and rigid pedicle screw-rod instrumentation. The periapical distraction device caused a significant ( P < .05) decrease in ROM of FE (human, -40.0% and porcine, -55.9%) and LB (human, -18.2% and porcine, -17.9%) as compared to the untreated spine, while ROM of AR remained unaffected. In comparison, rigid instrumentation caused a significantly ( P < .05) larger decrease in ROM of FE (human, -80.9% and porcine, -94.0%), LB (human, -75.0% and porcine, -92.2%), and AR (human, -71.3% and porcine, -86.9%). Although no destructive forces were applied, no device failures were observed. Spinal ROM was significantly less constrained by the periapical distraction device compared to rigid pedicle screw-rod instrumentation. Therefore, provided that scoliosis correction is achieved, a more physiological spinal motion is expected after scoliosis correction with the posterior concave periapical distraction device.

Mode of anesthesia and postoperative symptoms following abdominal hysterectomy in a fast-track setting.

PubMed

Wodlin, Ninnie Borendal; Nilsson, Lena; Arestedt, Kristofer; Kjølhede, Preben

2011-04-01

To determine whether postoperative symptoms differ between women who undergo abdominal benign hysterectomy in a fast-track model under general anesthesia or spinal anesthesia with intrathecal morphine. Secondary analysis from a randomized, open, multicenter study. Five hospitals in south-east Sweden. One-hundred and eighty women scheduled for benign hysterectomy were randomized; 162 completed the study; 82 were allocated to spinal and 80 to general anesthesia. The Swedish Postoperative Symptoms Questionnaire, completed daily for 1 week and thereafter once a week until 5 weeks postoperatively. Occurrence, intensity and duration of postoperative symptoms. Women who had hysterectomy under spinal anesthesia with intrathecal morphine experienced significantly less discomfort postoperatively compared with those who had the operation under general anesthesia. Spinal anesthesia reduced the need for opioids postoperatively. The most common symptoms were pain, nausea and vomiting, itching, drowsiness and fatigue. Abdominal pain, drowsiness and fatigue occurred significantly less often and with lower intensity among the spinal anesthesia group. Although postoperative nausea and vomiting was reported equally in the two groups, vomiting episodes were reported significantly more often during the first day after surgery in the spinal anesthesia group. Spinal anesthesia was associated with a higher prevalence of postoperative itching. Spinal anesthesia with intrathecal morphine carries advantages regarding postoperative symptoms and recovery following fast-track abdominal hysterectomy. © 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

Coupling between the spinal cord and cervical vertebral column under tensile loading.

PubMed

Kroeker, Shannon G; Ching, Randal P

2013-02-22

Current neck injury criteria are based on structural failure of the spinal (vertebral) column without consideration of injury to the spinal cord. Since one of the primary functions of the vertebral column is to protect the cord, it stands to reason that a more refined measure of neck injury threshold would be the onset of spinal cord injury (SCI). This study investigated the relationship between axial strains in the cervical vertebral column and the spinal cord using an in vitro primate model (n=10) under continuous tensile loading. Mean failure loads occurred at 1951.5±396N with failure strains in the vertebral column of 16±5% at the level of failure. Average tensile strains in the spinal cord at failure were 11±5% resulting in a mean coupling ratio of 0.54±0.17 between C1 and C7. The level of peak strain measured in the spinal cord did not always occur at the location of vertebral column failure. Spinal cord strains were less than spine strains and coupling ratios were not significantly different along the length of the spine. The largest coupling ratio was measured in the atlanto-occipital joint whereas the smallest coupling ratio occurred at the adjacent C1-C2 joint. Copyright © 2012 Elsevier Ltd. All rights reserved.

A novel approach for assigning levels to monkey and human lumbosacral spinal cord based on ventral horn morphology

PubMed Central

Gross, Cassandra; Ellison, Brian; Buchman, Aron S.; Terasawa, Ei

2017-01-01

Proper identification of spinal cord levels is crucial for clinical-pathological and imaging studies in humans, but can be a challenge given technical limitations. We have previously demonstrated in non-primate models that the contours of the spinal ventral horn are determined by the position of motoneuron pools. These positions are preserved within and among individuals and can be used to identify lumbosacral spinal levels. Here we tested the hypothesis that this approach can be extended to identify monkey and human spinal levels. In 7 rhesus monkeys, we retrogradely labeled motoneuron pools that represent rostral, middle and caudal landmarks of the lumbosacral enlargement. We then aligned the lumbosacral enlargements among animals using absolute length, segmental level or a relative scale based upon rostral and caudal landmarks. Inter-animal matching of labeled motoneurons across the lumbosacral enlargement was most precise when using internal landmarks. We then reconstructed 3 human lumbosacral spinal cords, and aligned these based upon homologous internal landmarks. Changes in shape of the ventral horn were consistent among human subjects using this relative scale, despite marked differences in absolute length or age. These data suggest that the relative position of spinal motoneuron pools is conserved across species, including primates. Therefore, in clinical-pathological or imaging studies in humans, one can assign spinal cord levels to even single sections by matching ventral horn shape to standardized series. PMID:28542213

Core self-evaluations and Snyder's hope theory in persons with spinal cord injuries.

PubMed

Smedema, Susan Miller; Chan, Jacob Yuichung; Phillips, Brian N

2014-11-01

The objective of the study was to evaluate a motivational model of core self-evaluations (CSE), hope (agency and pathways thinking), participation, and life satisfaction in persons with spinal cord injuries. A cross-sectional, correlational design with path analysis was used to evaluate the model. 187 adults with spinal cord injuries participated in this study. The results indicated an excellent fit between the data and the proposed model. Specifically, CSE was found to directly predict agency and pathways thinking, participation, and life satisfaction. CSE was also found to indirectly predict participation and life satisfaction through agency thinking. Although CSE contributes directly to participation and life satisfaction, it also has a unique role in increasing individuals' motivation to pursue goals, which also predicts participation and life satisfaction. Counseling interventions should be multifaceted and address the components of CSE to increase hope, participation, and life satisfaction. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Accelerated recovery of sensorimotor function in a dog submitted to quasi-total transection of the cervical spinal cord and treated with PEG.

PubMed

Kim, C-Yoon; Hwang, In-Kyu; Kim, Hana; Jang, Se-Woong; Kim, Hong Seog; Lee, Won-Young

2016-01-01

A case report on observing the recovery of sensory-motor function after cervical spinal cord transection. Laminectomy and transection of cervical spinal cord (C5) was performed on a male beagle weighing 3.5 kg. After applying polyethylene glycol (PEG) on the severed part, reconstruction of cervical spinal cord was confirmed by the restoration of sensorimotor function. Tetraplegia was observed immediately after operation, however, the dog showed stable respiration and survival without any complication. The dog showed fast recovery after 1 week, and recovered approximately 90% of normal sensorimotor function 3 weeks after the operation, although urinary disorder was still present. All recovery stages were recorded by video camera twice a week for behavioral analysis. While current belief holds that functional recovery is impossible after a section greater than 50% at C5-6 in the canine model, this case study shows the possibility of cervical spinal cord reconstruction after near-total transection. Furthermore, this case study also confirms that PEG can truly expedite the recovery of sensorimotor function after cervical spinal cord sections in dogs.

Computational Modeling of Inflammation and Wound Healing

PubMed Central

Ziraldo, Cordelia; Mi, Qi; An, Gary; Vodovotz, Yoram

2013-01-01

Objective Inflammation is both central to proper wound healing and a key driver of chronic tissue injury via a positive-feedback loop incited by incidental cell damage. We seek to derive actionable insights into the role of inflammation in wound healing in order to improve outcomes for individual patients. Approach To date, dynamic computational models have been used to study the time evolution of inflammation in wound healing. Emerging clinical data on histo-pathological and macroscopic images of evolving wounds, as well as noninvasive measures of blood flow, suggested the need for tissue-realistic, agent-based, and hybrid mechanistic computational simulations of inflammation and wound healing. Innovation We developed a computational modeling system, Simple Platform for Agent-based Representation of Knowledge, to facilitate the construction of tissue-realistic models. Results A hybrid equation–agent-based model (ABM) of pressure ulcer formation in both spinal cord-injured and -uninjured patients was used to identify control points that reduce stress caused by tissue ischemia/reperfusion. An ABM of arterial restenosis revealed new dynamics of cell migration during neointimal hyperplasia that match histological features, but contradict the currently prevailing mechanistic hypothesis. ABMs of vocal fold inflammation were used to predict inflammatory trajectories in individuals, possibly allowing for personalized treatment. Conclusions The intertwined inflammatory and wound healing responses can be modeled computationally to make predictions in individuals, simulate therapies, and gain mechanistic insights. PMID:24527362

Head and Spinal Cord Trauma Involving Youth Recreational Activities. Research Update.

ERIC Educational Resources Information Center

McAleese, Willis J.; Scantling, Ed

1996-01-01

Summarizes what current research on head and spinal cord injuries sustained during participation in recreation has to offer practitioners in terms of awareness and possible preventive strategies. It noted that by addressing injury prevention through the health-belief model paradigm, recreation practitioners move a step beyond simply providing…

Neuroprotective Potential of Gentongping in Rat Model of Cervical Spondylotic Radiculopathy Targeting PPAR-γ Pathway.

PubMed

Sun, Wen; Zheng, Kang; Liu, Bin; Fan, Danping; Luo, Hui; Qu, Xiaoyuan; Li, Li; He, Xiaojuan; Yi, Jianfeng; Lu, Cheng

2017-01-01

Cervical spondylotic radiculopathy (CSR) is the most general form of spinal degenerative disease and is characterized by pain and numbness of the neck and arm. Gentongping (GTP) granule, as a classical Chinese patent medicine, has been widely used in curing CSR, whereas the underlying mechanism remains unclear. Therefore, the aim of this study is to explore the pharmacological mechanisms of GTP on CSR. The rat model of CSR was induced by spinal cord injury (SCI). Our results showed that GTP could significantly alleviate spontaneous pain as well as ameliorate gait. The HE staining and Western blot results showed that GTP could increase the quantity of motoneuron and enhance the activation of peroxisome proliferator-activated receptor gamma (PPAR- γ ) in the spinal cord tissues. Meanwhile, immunofluorescence staining analysis indicated that GTP could reduce the expression of TNF- α in the spinal cord tissues. Furthermore, the protein level of Bax was decreased whereas the protein levels of Bcl-2 and NF200 were increased after the GTP treatment. These findings demonstrated that GTP might modulate the PPAR- γ pathway by inhibiting the inflammatory response and apoptosis as well as by protecting the cytoskeletal integrity of the spinal cord, ultimately play a neuroprotective role in CSR.

Leaky gate model: intensity-dependent coding of pain and itch in the spinal cord

PubMed Central

Sun, Shuohao; Xu, Qian; Guo, Changxiong; Guan, Yun; Liu, Qin; Dong, Xinzhong

2017-01-01

SUMMARY Coding of itch versus pain has been heatedly debated for decades. However, the current coding theories (labeled line, intensity and selectivity theory) cannot accommodate all experimental observations. Here we identified a subset of spinal interneurons, labeled by gastrin releasing peptide (Grp), that receive direct synaptic input from both pain and itch primary sensory neurons. When activated, these Grp+ neurons generated rarely-seen simultaneous robust pain and itch responses that were intensity-dependent. Accordingly, we propose a “leaky gate” model, in which Grp+ neurons transmit both itch and weak pain signals, however upon strong painful stimuli the recruitment of endogenous opioids works to close this gate, reducing overwhelming pain generated by parallel pathways. Consistent with our model, loss of these Grp+ neurons increased pain responses while itch was decreased. Our new model serves as an example of non-monotonic coding in the spinal cord and better explains observations in human psychophysical studies. PMID:28231466

Quantifying the Risk of Spinal Injury in Motor Vehicle Collisions According to Ambulatory Status: A Prospective Analytical Study.

PubMed

McCoy, Christopher Eric; Loza-Gomez, Angelica; Lee Puckett, James; Costantini, Samantha; Penalosa, Patrick; Anderson, Craig; Schultz, Carl

2017-02-01

The association between ambulation at the scene of a motor vehicle collision (MVC) and spinal injury has never been quantified. To evaluate the association between ambulation and spinal injury in patients involved in a MVC. Prospective analytical-observational cohort study. Inclusion: patients sustaining traumatic injury in a MVC. Exclusion: < 18 years old, pregnancy. spinal injury defined as injury to the cervical, thoracic, or lumbar spinal cord, bones, or ligaments. Secondary outcome: Injury resulting in neurological deficit, need for surgery, or death. A generalized linear model was used to evaluate the association between outcome and predictor variables. Risk ratios [RR] were reported with a point estimate and 95% confidence interval (CI). A two-tailed alpha of < 0.05 was the threshold for statistical significance. There were 704 patients analyzed. Nonambulatory patients were 2.29 times more likely to sustain a spinal injury, compared to ambulatory patients (RR 2.29, 95% CI 1.34-3.91). Patients ≥ 65 years of age were 3.27 times more likely to sustain a spinal injury (RR 3.27, 95% CI 1.66-6.45). Patients with a Glasgow Coma Scale score ≤ 8 were 4.93 times more likely to sustain a spinal injury (RR 4.93, 95% CI 1.86-13.10). In this prospective analytical-observational study evaluating the association between ambulatory status and spinal injury in patients involved in MVCs, we observed that those patients who were nonambulatory were more than two times as likely to have a spinal injury compared to those patients who were ambulatory at the scene. Copyright © 2016 Elsevier Inc. All rights reserved.

Transcranial magnetic stimulation (TMS) responses elicited in hindlimb muscles as an assessment of synaptic plasticity in spino-muscular circuitry after chronic spinal cord injury.

PubMed

Petrosyan, Hayk A; Alessi, Valentina; Sisto, Sue A; Kaufman, Mark; Arvanian, Victor L

2017-03-06

Electromagnetic stimulation applied at the cranial level, i.e. transcranial magnetic stimulation (TMS), is a technique for stimulation and neuromodulation used for diagnostic and therapeutic applications in clinical and research settings. Although recordings of TMS elicited motor-evoked potentials (MEP) are an essential diagnostic tool for spinal cord injured (SCI) patients, they are reliably recorded from arm, and not leg muscles. Mid-thoracic contusion is a common SCI that results in locomotor impairments predominantly in legs. In this study, we used a chronic T10 contusion SCI rat model and examined whether (i) TMS-responses in hindlimb muscles can be used for evaluation of conduction deficits in cortico-spinal circuitry and (ii) if plastic changes at spinal levels will affect these responses. In this study, plastic changes of transmission in damaged spinal cord were achieved by repetitive electro-magnetic stimulation applied over the spinal level (rSEMS). Spinal electro-magnetic stimulation was previously shown to activate spinal nerves and is gaining large acceptance as a non-invasive alternative to direct current and/or epidural electric stimulation. Results demonstrate that TMS fails to induce measurable MEPs in hindlimbs of chronically SCI animals. After facilitation of synaptic transmission in damaged spinal cord was achieved with rSEMS, however, MEPs were recorded from hindlimb muscles in response to single pulse TMS stimulation. These results provide additional evidence demonstrating beneficial effects of TMS as a diagnostic technique for descending motor pathways in uninjured CNS and after SCI. This study confirms the ability of TMS to assess plastic changes of transmission occurring at the spinal level. Published by Elsevier B.V.

Challenges of transcutaneous laser application for the potential of photobiomodulation of the spinal cord at the scale of a large companion animal

NASA Astrophysics Data System (ADS)

Piao, Daqing; Sypniewski, Lara A.; Bartels, Kenneth E.

2017-02-01

Photobiomodulation (PBM) has been used successfully for the treatment of nervous system and has been demonstrated in the rodent model. In contrast, the percutaneous use of PBM to treat spinal cord of companion animals is expected to be challenging due to the significant attenuation of light energy as it travels through the thick and heterogeneous layers of tissue and bone to reach the level of the spinal cord. This pilot study was performed on a cadaverous dog to determine if the recommended bio-stimulatory treatment dose can be delivered to the spinal canal via percutaneous application of a clinically acceptable surface dose. The dose reaching the spinal canal after percutaneous application was measured at 980nm by using a miniature photo-diode sensor with a dose-response sensitivity of 1V per 1mW/cm2 dose and a 2mm spherical isotropic fiber-optical diffusor probe. The two sensors were embedded in different longitudinal positions along the dorsal portion of the spinal canal just below the soft tissues and vertebral processes in a 40lbs cadaverous dog. The spinal cord was then accessed via a hemilaminectomy. Once embedded in the target tissue, 1W-10 W surface irradiation was applied. At the T12/13 and T13/L1 intervertebral disc positions, photo-diode sensors detected the intra-spinal dose above the noise floor at the 10W surface dose. A narrow treatment window for percutaneous PBM in large dog may exist only for the shallowest segment of the spinal cord, which may be important to avoid potential collateral photothermal effects. Works for simultaneous multi-site intra-spinal measurements are on-going.

Willingness to Pay for a Newborn Screening Test for Spinal Muscular Atrophy.

PubMed

Lin, Pei-Jung; Yeh, Wei-Shi; Neumann, Peter J

2017-01-01

The current US mandatory newborn screening panel does not include spinal muscular atrophy, the most common fatal genetic disease among children. We assessed population preferences for newborn screening for spinal muscular atrophy, and how test preferences varied depending on immediate treatment implications. We conducted an online willingness-to-pay survey of US adults (n = 982). Respondents were asked to imagine being parents of a newborn. Each respondent was presented with two hypothetical scenarios following the spinal muscular atrophy screening test: current standard of care (no treatment available) and one of three randomly assigned scenarios (new treatment available to improve functioning, survival, or both). We used a bidding game to elicit willingness to pay for the spinal muscular atrophy test, and performed a two-part model to estimate median and mean willingness-to-pay values. Most respondents (79% to 87%) would prefer screening their newborns for spinal muscular atrophy. People expressed a willingness to pay for spinal muscular atrophy screening even without an available therapy (median: $142; mean: $253). Willingness to pay increased with treatment availability (median: $161 to $182; mean: $270 to $297) and respondent income. Most respondents considered test accuracy, treatment availability, and treatment effectiveness very important or important factors in deciding willingness to pay. Most people would prefer and would be willing to pay for testing their newborn for spinal muscular atrophy, even in the absence of direct treatment. People perceive the spinal muscular atrophy test more valuable if treatment were available to improve the newborn's functioning and survival. Despite preferences for the test information, adding spinal muscular atrophy to newborn screening programs remains controversial. Future studies are needed to determine how early detection may impact long-term patient outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

The modulatory role of spinally located histamine receptors in the regulation of the blood glucose level in d-glucose-fed mice.

PubMed

Sim, Yun-Beom; Park, Soo-Hyun; Kim, Sung-Su; Kim, Chea-Ha; Kim, Su-Jin; Lim, Su-Min; Jung, Jun-Sub; Ryu, Ohk-Hyun; Choi, Moon-Gi; Suh, Hong-Won

2014-02-01

The possible roles of spinal histamine receptors in the regulation of the blood glucose level were studied in ICR mice. Mice were intrathecally (i.t.) treated with histamine 1 (H1) receptor agonist (2-pyridylethylamine) or antagonist (cetirizine), histamine 2 (H2) receptor agonist (dimaprit) or antagonist (ranitidine), histamine 3 (H3) receptor agonist (α-methylhistamine) or antagonist (carcinine) and histamine 4 (H4) receptor agonist (VUF 8430) or antagonist (JNJ 7777120), and the blood glucose level was measured at 30, 60 and 120 min after i.t. administration. The i.t. injection with α-methylhistamine, but not carcinine slightly caused an elevation of the blood glucose level. In addition, histamine H1, H2, and H4 receptor agonists and antagonists did not affect the blood glucose level. In D-glucose-fed model, i.t. pretreatment with cetirizine enhanced the blood glucose level, whereas 2-pyridylethylamine did not affect. The i.t. pretreatment with dimaprit, but not ranitidine, enhanced the blood glucose level in D-glucose-fed model. In addition, α-methylhistamine, but not carcinine, slightly but significantly enhanced the blood glucose level D-glucose-fed model. Finally, i.t. pretreatment with JNJ 7777120, but not VUF 8430, slightly but significantly increased the blood glucose level. Although histamine receptors themselves located at the spinal cord do not exert any effect on the regulation of the blood glucose level, our results suggest that the activation of spinal histamine H2 receptors and the blockade of spinal histamine H1 or H3 receptors may play modulatory roles for up-regulation and down-regulation, respectively, of the blood glucose level in D-glucose fed model.

Bio-Inspired Controller on an FPGA Applied to Closed-Loop Diaphragmatic Stimulation

PubMed Central

Zbrzeski, Adeline; Bornat, Yannick; Hillen, Brian; Siu, Ricardo; Abbas, James; Jung, Ranu; Renaud, Sylvie

2016-01-01

Cervical spinal cord injury can disrupt connections between the brain respiratory network and the respiratory muscles which can lead to partial or complete loss of ventilatory control and require ventilatory assistance. Unlike current open-loop technology, a closed-loop diaphragmatic pacing system could overcome the drawbacks of manual titration as well as respond to changing ventilation requirements. We present an original bio-inspired assistive technology for real-time ventilation assistance, implemented in a digital configurable Field Programmable Gate Array (FPGA). The bio-inspired controller, which is a spiking neural network (SNN) inspired by the medullary respiratory network, is as robust as a classic controller while having a flexible, low-power and low-cost hardware design. The system was simulated in MATLAB with FPGA-specific constraints and tested with a computational model of rat breathing; the model reproduced experimentally collected respiratory data in eupneic animals. The open-loop version of the bio-inspired controller was implemented on the FPGA. Electrical test bench characterizations confirmed the system functionality. Open and closed-loop paradigm simulations were simulated to test the FPGA system real-time behavior using the rat computational model. The closed-loop system monitors breathing and changes in respiratory demands to drive diaphragmatic stimulation. The simulated results inform future acute animal experiments and constitute the first step toward the development of a neuromorphic, adaptive, compact, low-power, implantable device. The bio-inspired hardware design optimizes the FPGA resource and time costs while harnessing the computational power of spike-based neuromorphic hardware. Its real-time feature makes it suitable for in vivo applications. PMID:27378844

Why do spinal manipulation techniques take the form they do? Towards a general model of spinal manipulation.

PubMed

Evans, David W

2010-06-01

For centuries, techniques used to manipulate joints in the spine have been passed down from one generation of manipulators to the next. Today, spinal manipulation is in the curious position that positive clinical effects have now been demonstrated, yet the theoretical base underpinning every aspect of its use is still underdeveloped. An important question is posed in this masterclass: why do spinal manipulation techniques take the form they do? From the available literature, two factors appear to provide an answer: 1. Action of a force upon vertebrae. Any 'direct' spinal manipulation technique requires that the patient be orientated in such a way that force is applied perpendicular to the overlying skin surface so as to act upon the vertebrae beneath. If the vertebral motion produced by 'directly' applied force is insufficient to produce the desired effect (e.g. cavitation), then force must be applied 'indirectly', often through remote body segments such as the head, thorax, abdomen, pelvis, and extremities. 2. Spinal segment morphology. A new hypothesis is presented. Spinal manipulation techniques exploit the morphology of vertebrae by inducing rotation at a spinal segment, about an axis that is always parallel to the articular surfaces of the constituent zygapophysial joints. In doing so, the articular surfaces of one zygapophysial joint appose to the point of contact, resulting in migration of the axis of rotation towards these contacting surfaces, and in turn this facilitates gapping of the other (target) zygapophysial joint. Other variations in the form of spinal manipulation techniques are likely to depend upon the personal style and individual choices of the practitioner.

Quantifying the Nonlinear, Anisotropic Material Response of Spinal Ligaments

NASA Astrophysics Data System (ADS)

Robertson, Daniel J.

Spinal ligaments may be a significant source of chronic back pain, yet they are often disregarded by the clinical community due to a lack of information with regards to their material response, and innervation characteristics. The purpose of this dissertation was to characterize the material response of spinal ligaments and to review their innervation characteristics. Review of relevant literature revealed that all of the major spinal ligaments are innervated. They cause painful sensations when irritated and provide reflexive control of the deep spinal musculature. As such, including the neurologic implications of iatrogenic ligament damage in the evaluation of surgical procedures aimed at relieving back pain will likely result in more effective long-term solutions. The material response of spinal ligaments has not previously been fully quantified due to limitations associated with standard soft tissue testing techniques. The present work presents and validates a novel testing methodology capable of overcoming these limitations. In particular, the anisotropic, inhomogeneous material constitutive properties of the human supraspinous ligament are quantified and methods for determining the response of the other spinal ligaments are presented. In addition, a method for determining the anisotropic, inhomogeneous pre-strain distribution of the spinal ligaments is presented. The multi-axial pre-strain distributions of the human anterior longitudinal ligament, ligamentum flavum and supraspinous ligament were determined using this methodology. Results from this work clearly demonstrate that spinal ligaments are not uniaxial structures, and that finite element models which account for pre-strain and incorporate ligament's complex material properties may provide increased fidelity to the in vivo condition.

Quadriplegia recovery after hemi-section and transplant model of spinal cord at the level of C5 and C6.

PubMed

Bitar-Alatorre, W E; Segura-Torres, J E; Rosales-Corral, S A; Jiménez-Avila, J M; Huerta-Viera, M

2011-03-10

A spinal cord hemi-section with a homologous transplant of medullar tissue at the level of C5-C6 and preservation of the anterior spinal artery was used to evaluate the histological characteristics such as quantity and quality of axons, myelin index and blood vessels after quadriplegia recovery. Vascular changes after spinal injury results in severe endothelial damage, axonal edema, neuronal necrosis and demyelinization as well as cysts and infarction. Preservation of the anterior spinal artery has demonstrated clinical recuperation; therefore, in addition to the lesion we included a homologous transplant to visualize changes at a cellular level. Two groups of dogs (hemi-section and transplant) went through a traumatic spinal cord hemi-section of 50% at the level of C5-C6. The transplant group formed by animals which simultaneously had 4 mm of spinal cord removed and the equal amount substituted from a donor animal at the level of C5-C6 corresponding to the half right side; both preserving the anterior spinal artery. Histological evaluation of all groups took place at days 3 (acute) and 28 (chronic) post-operation. Changes of degeneration and axonal regeneration were found in the hemi-section and transplant groups at acute and chronic time, as well as same quadriplegia recovery at chronic time in the hemi-section and transplant groups which closely related to mechanisms which participate in regeneration and functional recuperation due to the preservation of the anterior spinal artery and presence of new blood vessels. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Neuroprotective effects of Ganoderma lucidum polysaccharides against traumatic spinal cord injury in rats.

PubMed

Gokce, Emre Cemal; Kahveci, Ramazan; Atanur, Osman Malik; Gürer, Bora; Aksoy, Nurkan; Gokce, Aysun; Sargon, Mustafa Fevzi; Cemil, Berker; Erdogan, Bulent; Kahveci, Ozan

2015-11-01

Ganoderma lucidum (G. lucidum) is a mushroom belonging to the polyporaceae family of Basidiomycota and has widely been used as a traditional medicine for thousands of years. G. lucidum has never been studied in traumatic spinal cord injury. The aim of this study is to investigate whether G. lucidum polysaccharides (GLPS) can protect the spinal cord after experimental spinal cord injury. Rats were randomized into five groups of eight animals each: control, sham, trauma, GLPS, and methylprednisolone. In the control group, no surgical intervention was performed. In the sham group, only a laminectomy was performed. In all the other groups, the spinal cord trauma model was created by the occlusion of the spinal cord with an aneurysm clip. In the spinal cord tissue, caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, nitric oxide levels, and superoxide dismutase levels were analysed. Histopathological and ultrastructural evaluations were also performed. Neurological evaluation was performed using the Basso, Beattie, and Bresnahan locomotor scale and the inclined-plane test. After traumatic spinal cord injury, increases in caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, and nitric oxide levels were detected. After the administration of GLPS, decreases were observed in tissue caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, and nitric oxide levels. Furthermore, GLPS treatment showed improved results in histopathological scores, ultrastructural scores, and functional tests. Biochemical, histopathological, and ultrastructural analyses and functional tests reveal that GLPS exhibits meaningful neuroprotective effects against spinal cord injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Neuroprotective Effect of Kefir on Spinal Cord Ischemia/Reperfusion Injury in Rats.

PubMed

Guven, Mustafa; Akman, Tarik; Yener, Ali Umit; Sehitoglu, Muserref Hilal; Yuksel, Yasemin; Cosar, Murat

2015-05-01

The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of kefir on spinal cord ischemia injury in rats. Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (p<0.05). Catalase and superoxide dismutase levels of the kefir group were significantly higher than ischemia group (p<0.05). In histopathological samples, the kefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (p<0.05). In immunohistochemical staining, hipoxia-inducible factor-1α and caspase 3 immunopositive neurons were significantly decreased in kefir group compared with ischemia group (p<0.05). The neurological deficit scores of kefir group were significantly higher than ischemia group at 24 h (p<0.05). Our study revealed that kefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future.

Right-sided vagus nerve stimulation inhibits induced spinal cord seizures.

PubMed

Tubbs, R Shane; Salter, E George; Killingsworth, Cheryl; Rollins, Dennis L; Smith, William M; Ideker, Raymond E; Wellons, John C; Blount, Jeffrey P; Oakes, W Jerry

2007-01-01

We have previously shown that left-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. To test our hypothesis that right-sided vagus nerve stimulation will also abort seizure activity, we have initiated seizures in the spinal cord and then performed right-sided vagus nerve stimulation in an animal model. Four pigs were anesthetized and placed in the lateral position and a small laminectomy performed in the lumbar region. Topical penicillin, a known epileptogenic drug to the cerebral cortex and spinal cord, was next applied to the dorsal surface of the exposed cord. With the exception of the control animal, once seizure activity was discernible via motor convulsion or increased electrical activity, the right vagus nerve previously isolated in the neck was stimulated. Following multiple stimulations of the vagus nerve and with seizure activity confirmed, the cord was transected in the midthoracic region and vagus nerve stimulation performed. Right-sided vagus nerve stimulation resulted in cessation of spinal cord seizure activity in all animals. Transection of the spinal cord superior to the site of seizure induction resulted in the ineffectiveness of vagus nerve stimulation in causing cessation of seizure activity in all study animals. As with left-sided vagus nerve stimulation, right-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. Additionally, the effects of right-sided vagus nerve stimulation on induced spinal cord seizures involve descending spinal pathways. These data may aid in the development of alternative mechanisms for electrical stimulation for patients with medically intractable seizures and add to our knowledge regarding the mechanism for seizure cessation following peripheral nerve stimulation.

Bone mesenchymal stem cells attenuate radicular pain by inhibiting microglial activation in a rat noncompressive disk herniation model.

PubMed

Huang, Xiaodong; Wang, Weiheng; Liu, Xilin; Xi, Yanhai; Yu, Jiangming; Yang, Xiangqun; Ye, Xiaojian

2018-06-01

Spinal disk herniation can induce radicular pain through chemical irritation caused by proinflammatory and immune responses. Bone marrow mesenchymal stem cells (BMSCs) are a unique type of adult stem cell with the functions of suppressing inflammation and modulating immune responses. This study was undertaken to observe the effect of intrathecal BMSCs on the treatment of mechanical allodynia and the suppression of microglial activation in a rat noncompressive disk herniation model. The model was induced by the application of nucleus pulposus (NP) to the L5 dorsal root ganglion (DRG). The study found that the use of NP in the DRG can induce abnormal mechanical pain, increase the contents of the proinflammatory factors TNF-α and IL-1β, decrease the content of the anti-inflammatory cytokine TGF-β1 and activate microglia in the spinal dorsal horns (L5) (P < 0.05). BMSC administration could increase the mechanical withdrawal thresholds dramatically, decrease the contents of IL-1β and TNF-α, increase the content of TGF-β1 significantly (P < 0.05) and inhibit microglial activation in the bilateral spinal dorsal horn. Our results indicate that BMSC administration can reduce mechanical allodynia and downregulate the expression of proinflammatory cytokines by inhibiting microglial activation in the spinal dorsal horn in a rat noncompressive disk herniation model.

Overexpression of survival motor neuron improves neuromuscular function and motor neuron survival in mutant SOD1 mice.

PubMed

Turner, Bradley J; Alfazema, Neza; Sheean, Rebecca K; Sleigh, James N; Davies, Kay E; Horne, Malcolm K; Talbot, Kevin

2014-04-01

Spinal muscular atrophy results from diminished levels of survival motor neuron (SMN) protein in spinal motor neurons. Low levels of SMN also occur in models of amyotrophic lateral sclerosis (ALS) caused by mutant superoxide dismutase 1 (SOD1) and genetic reduction of SMN levels exacerbates the phenotype of transgenic SOD1(G93A) mice. Here, we demonstrate that SMN protein is significantly reduced in the spinal cords of patients with sporadic ALS. To test the potential of SMN as a modifier of ALS, we overexpressed SMN in 2 different strains of SOD1(G93A) mice. Neuronal overexpression of SMN significantly preserved locomotor function, rescued motor neurons, and attenuated astrogliosis in spinal cords of SOD1(G93A) mice. Despite this, survival was not prolonged, most likely resulting from SMN mislocalization and depletion of gems in motor neurons of symptomatic mice. Our results reveal that SMN upregulation slows locomotor deficit onset and motor neuron loss in this mouse model of ALS. However, disruption of SMN nuclear complexes by high levels of mutant SOD1, even in the presence of SMN overexpression, might limit its survival promoting effects in this specific mouse model. Studies in emerging mouse models of ALS are therefore warranted to further explore the potential of SMN as a modifier of ALS. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of Tanshinone IIa on heat shock protein 70, Bcl-2 and Bax expression in rats with spinal ischemia/reperfusion injury☆

PubMed Central

Zhang, Li; Gan, Weidong; An, Guoyao

2012-01-01

Tanshinone IIa is an effective monomer component of Danshen, which is a traditional Chinese medicine for activating blood circulation to dissipate blood stasis. Tanshinone IIa can effectively improve brain tissue ischemia/hypoxia injury. The present study established a rat model of spinal cord ischemia/reperfusion injury and intraperitoneally injected Tanshinone IIa, 0.5 hour prior to model establishment. Results showed that Tanshinone IIa promoted heat shock protein 70 and Bcl-2 protein expression, but inhibited Bax protein expression in the injured spinal cord after ischemia/reperfusion injury. Furthermore, Nissl staining indicated a reduction in nerve cell apoptosis and fewer pathological lesions in the presence of Tanshinone IIa, compared with positive control Danshen injection. PMID:25317140

The Spinal Cord Injury- Functional Index: Item Banks to Measure Physical Functioning of Individuals with Spinal Cord Injury

PubMed Central

Tulsky, David S.; Jette, Alan; Kisala, Pamela A.; Kalpakjian, Claire; Dijkers, Marcel P.; Whiteneck, Gale; Ni, Pengsheng; Kirshblum, Steven; Charlifue, Susan; Heinemann, Allen W.; Forchheimer, Martin; Slavin, Mary; Houlihan, Bethlyn; Tate, Denise; Dyson-Hudson, Trevor; Fyffe, Denise; Williams, Steve; Zanca, Jeanne

2012-01-01

Objective To develop a comprehensive set of patient reported items to assess multiple aspects of physical functioning relevant to the lives of people with spinal cord injury (SCI) and to evaluate the underlying structure of physical functioning. Design Cross-sectional Setting Inpatient and community Participants Item pools of physical functioning were developed, refined and field tested in a large sample of 855 individuals with traumatic spinal cord injury stratified by diagnosis, severity, and time since injury Interventions None Main Outcome Measure SCI-FI measurement system Results Confirmatory factor analysis (CFA) indicated that a 5-factor model, including basic mobility, ambulation, wheelchair mobility, self care, and fine motor, had the best model fit and was most closely aligned conceptually with feedback received from individuals with SCI and SCI clinicians. When just the items making up basic mobility were tested in CFA, the fit statistics indicate strong support for a unidimensional model. Similar results were demonstrated for each of the other four factors indicating unidimensional models. Conclusions Though unidimensional or 2-factor (mobility and upper extremity) models of physical functioning make up outcomes measures in the general population, the underlying structure of physical function in SCI is more complex. A 5-factor solution allows for comprehensive assessment of key domain areas of physical functioning. These results informed the structure and development of the SCI-FI measurement system of physical functioning. PMID:22609299

Time-dependent, bidirectional, anti- and pro-spinal hyper-reflexia and muscle spasticity effect after chronic spinal glycine transporter 2 (GlyT2) oligonucleotide-induced downregulation.

PubMed

Kamizato, Kota; Marsala, Silvia; Navarro, Michael; Kakinohana, Manabu; Platoshyn, Oleksandr; Yoshizumi, Tetsuya; Lukacova, Nadezda; Wancewicz, Ed; Powers, Berit; Mazur, Curt; Marsala, Martin

2018-07-01

The loss of local spinal glycine-ergic tone has been postulated as one of the mechanisms contributing to the development of spinal injury-induced spasticity. In our present study using a model of spinal transection-induced muscle spasticity, we characterize the effect of spinally-targeted GlyT2 downregulation once initiated at chronic stages after induction of spasticity in rats. In animals with identified hyper-reflexia, the anti-spasticity effect was studied after intrathecal treatment with: i) glycine, ii) GlyT2 inhibitor (ALX 1393), and iii) GlyT2 antisense oligonucleotide (GlyT2-ASO). Administration of glycine and GlyT2 inhibitor led to significant suppression of spasticity lasting for a minimum of 45-60 min. Treatment with GlyT2-ASO led to progressive suppression of muscle spasticity seen at 2-3 weeks after treatment. Over the subsequent 4-12 weeks, however, the gradual appearance of profound spinal hyper-reflexia was seen. This was presented as spontaneous or slight-tactile stimulus-evoked muscle oscillations in the hind limbs (but not in upper limbs) with individual hyper-reflexive episodes lasting between 3 and 5 min. Chronic hyper-reflexia induced by GlyT2-ASO treatment was effectively blocked by intrathecal glycine. Immunofluorescence staining and Q-PCR analysis of the lumbar spinal cord region showed a significant (>90%) decrease in GlyT2 mRNA and GlyT2 protein. These data demonstrate that spinal GlyT2 downregulation provides only a time-limited therapeutic benefit and that subsequent loss of glycine vesicular synthesis resulting from chronic GlyT2 downregulation near completely eliminates the tonic glycine-ergic activity and is functionally expressed as profound spinal hyper-reflexia. These characteristics also suggest that chronic spinal GlyT2 silencing may be associated with pro-nociceptive activity. Copyright © 2018 Elsevier Inc. All rights reserved.

Spinal intracellular metabotropic glutamate receptor 5 (mGluR5) contributes to pain and c-fos expression in a rat model of inflammatory pain.

PubMed

Vincent, Kathleen; Wang, Shu Fan; Laferrière, André; Kumar, Naresh; Coderre, Terence J

2017-04-01

Metabotropic glutamate receptor 5 (mGluR5) is an excitatory G-protein-coupled receptor (GPCR) present in the spinal cord dorsal horn (SCDH) where it has a well-established role in pain. In addition to its traditional location on the cytoplasmic membrane, recent evidence shows that these receptors are present intracellularly on the nuclear membrane in the spinal cord dorsal horn and are implicated in neuropathic pain. Nuclear mGluR5 is a functional receptor that binds glutamate entering the cell through the neuronal glutamate transporter (GT) EAAT3 and activates transcription factor c-fos, whereas plasma membrane mGluR5 is responsible for c-jun activation. Here, we extend these findings to a model of inflammatory pain using complete Freund's adjuvant (CFA) and show that nuclear mGluR5 is also upregulated in the spinal cord dorsal horn following inflammation. We also show that pretreatment with an excitatory amino acid transporter (EAAT) inhibitor attenuates pain and decreases Fos, but not Jun, expression in complete Freund's adjuvant rats. In contrast, selective glial glutamate transporter inhibitors are pronociceptive and increase spinal glutamate concentrations. Additionally, we found that permeable mGluR5 antagonists are more effective at attenuating pain and Fos expression than nonpermeable group I mGluR antagonists. Taken together, these results suggest that under inflammatory conditions, intracellular mGluR5 is actively involved in the relay of nociceptive information in the spinal cord.

Elimination of Left-Right Reciprocal Coupling in the Adult Lamprey Spinal Cord Abolishes the Generation of Locomotor Activity

PubMed Central

Messina, J. A.; St. Paul, Alison; Hargis, Sarah; Thompson, Wengora E.; McClellan, Andrew D.

2017-01-01

The contribution of left-right reciprocal coupling between spinal locomotor networks to the generation of locomotor activity was tested in adult lampreys. Muscle recordings were made from normal animals as well as from experimental animals with rostral midline (ML) spinal lesions (~13%→35% body length, BL), before and after spinal transections (T) at 35% BL. Importantly, in the present study actual locomotor movements and muscle burst activity, as well as other motor activity, were initiated in whole animals by descending brain-spinal pathways in response to sensory stimulation of the anterior head. For experimental animals with ML spinal lesions, sensory stimulation could elicit well-coordinated locomotor muscle burst activity, but with some significant differences in the parameters of locomotor activity compared to those for normal animals. Computer models representing normal animals or experimental animals with ML spinal lesions could mimic many of the differences in locomotor activity. For experimental animals with ML and T spinal lesions, right and left rostral hemi-spinal cords, disconnected from intact caudal cord, usually produced tonic or unpatterned muscle activity. Hemi-spinal cords sometimes generated spontaneous or sensory-evoked relatively high frequency “burstlet” activity that probably is analogous to the previously described in vitro “fast rhythm”, which is thought to represent lamprey locomotor activity. However, “burstlet” activity in the present study had parameters and features that were very different than those for lamprey locomotor activity: average frequencies were ~25 Hz, but individual frequencies could be >50 Hz; burst proportions (BPs) often varied with cycled time; “burstlet” activity usually was not accompanied by a rostrocaudal phase lag; and following ML spinal lesions alone, “burstlet” activity could occur in the presence or absence of swimming burst activity, suggesting the two were generated by different mechanisms. In summary, for adult lampreys, left and right hemi-spinal cords did not generate rhythmic locomotor activity in response to descending inputs from the brain, suggesting that left-right reciprocal coupling of spinal locomotor networks contributes to both phase control and rhythmogenesis. In addition, the present study indicates that extreme caution should be exercised when testing the operation of spinal locomotor networks using artificial activation of isolated or reduced nervous system preparations. PMID:29225569

Dynamic neural network models of the premotoneuronal circuitry controlling wrist movements in primates.

PubMed

Maier, M A; Shupe, L E; Fetz, E E

2005-10-01

Dynamic recurrent neural networks were derived to simulate neuronal populations generating bidirectional wrist movements in the monkey. The models incorporate anatomical connections of cortical and rubral neurons, muscle afferents, segmental interneurons and motoneurons; they also incorporate the response profiles of four populations of neurons observed in behaving monkeys. The networks were derived by gradient descent algorithms to generate the eight characteristic patterns of motor unit activations observed during alternating flexion-extension wrist movements. The resulting model generated the appropriate input-output transforms and developed connection strengths resembling those in physiological pathways. We found that this network could be further trained to simulate additional tasks, such as experimentally observed reflex responses to limb perturbations that stretched or shortened the active muscles, and scaling of response amplitudes in proportion to inputs. In the final comprehensive network, motor units are driven by the combined activity of cortical, rubral, spinal and afferent units during step tracking and perturbations. The model displayed many emergent properties corresponding to physiological characteristics. The resulting neural network provides a working model of premotoneuronal circuitry and elucidates the neural mechanisms controlling motoneuron activity. It also predicts several features to be experimentally tested, for example the consequences of eliminating inhibitory connections in cortex and red nucleus. It also reveals that co-contraction can be achieved by simultaneous activation of the flexor and extensor circuits without invoking features specific to co-contraction.

Neuraxial blockade for external cephalic version: Cost analysis.

PubMed

Yamasato, Kelly; Kaneshiro, Bliss; Salcedo, Jennifer

2015-07-01

Neuraxial blockade (epidural or spinal anesthesia/analgesia) with external cephalic version increases the external cephalic version success rate. Hospitals and insurers may affect access to neuraxial blockade for external cephalic version, but the costs to these institutions remain largely unstudied. The objective of this study was to perform a cost analysis of neuraxial blockade use during external cephalic version from hospital and insurance payer perspectives. Secondarily, we estimated the effect of neuraxial blockade on cesarean delivery rates. A decision-analysis model was developed using costs and probabilities occurring prenatally through the delivery hospital admission. Model inputs were derived from the literature, national databases, and local supply costs. Univariate and bivariate sensitivity analyses and Monte Carlo simulations were performed to assess model robustness. Neuraxial blockade was cost saving to both hospitals ($30 per delivery) and insurers ($539 per delivery) using baseline estimates. From both perspectives, however, the model was sensitive to multiple variables. Monte Carlo simulation indicated neuraxial blockade to be more costly in approximately 50% of scenarios. The model demonstrated that routine use of neuraxial blockade during external cephalic version, compared to no neuraxial blockade, prevented 17 cesarean deliveries for every 100 external cephalic versions attempted. Neuraxial blockade is associated with minimal hospital and insurer cost changes in the setting of external cephalic version, while reducing the cesarean delivery rate. © 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.

Neuraxial blockade for external cephalic version: Cost analysis

PubMed Central

Yamasato, Kelly; Kaneshiro, Bliss; Salcedo, Jennifer

2017-01-01

Aim Neuraxial blockade (epidural or spinal anesthesia/analgesia) with external cephalic version increases the external cephalic version success rate. Hospitals and insurers may affect access to neuraxial blockade for external cephalic version, but the costs to these institutions remain largely unstudied. The objective of this study was to perform a cost analysis of neuraxial blockade use during external cephalic version from hospital and insurance payer perspectives. Secondarily, we estimated the effect of neuraxial blockade on cesarean delivery rates. Methods A decision–analysis model was developed using costs and probabilities occurring prenatally through the delivery hospital admission. Model inputs were derived from the literature, national databases, and local supply costs. Univariate and bivariate sensitivity analyses and Monte Carlo simulations were performed to assess model robustness. Results Neuraxial blockade was cost saving to both hospitals ($30 per delivery) and insurers ($539 per delivery) using baseline estimates. From both perspectives, however, the model was sensitive to multiple variables. Monte Carlo simulation indicated neuraxial blockade to be more costly in approximately 50% of scenarios. The model demonstrated that routine use of neuraxial blockade during external cephalic version, compared to no neuraxial blockade, prevented 17 cesarean deliveries for every 100 external cephalic versions attempted. Conclusions Neuraxial blockade is associated with minimal hospital and insurer cost changes in the setting of external cephalic version, while reducing the cesarean delivery rate. PMID:25771920

Neuronal regeneration in the newt: a model to study the partly reconstruction of the neural tissue in real and simulated weightles sness

NASA Astrophysics Data System (ADS)

Anton, H.; Grigoryan, E.; Mitashov, V.

The micro -"g" effect on nervous tissue regeneration in newts has been investigated by our group for many years. It has been performed in real and in simulated microgravity with a clinostat. During limb regeneration the motor - and sensory nerves regrow perfectly within the newly formed limb. Like in `1g' conditions they are responsible for the initiation of blastema formation and continuity of g owth andr differentiation. Except for a general acceleration of growth and differentiation processes no differences became visible. Tail regeneration, which is perfectly regulated in newts during their whole life, includes the restoration of the spinal cord and dorsal root ganglia. They follow or initiate an accelerated growth. Up to the present the cellular derivation of the sensory neurones within the regenerate has not yet been clarified. But growth acceleration comprises the whole nervous system. That means a totally new formation of the sensory connection from the periphery to the whole spinal cord. Regeneration must be initiated by the outgrowth of nerve fibres into the wound area. This may be performed by the remaining cut sensory fibres of the last stump segment and should be followed by the differentiation of undifferentiated cells of neural crest origin nearby the amputation area. Such cells are present in the form of meningeal cells which are the origin of mantle and Schwann cells too. Corresponding to the well proved growth acceleration of lens, retina, connective tissue, muscle and skin, the real and simulated microgravity affects the nervous system in the same manner. Tissues and organs of adult organisms have no chance to remain unaffected by the microgravity effect. We try to find the trigger which initiates the accelerated proliferation of the stem cells of sensory neurons, mantle and sheath cells under micro-"g" conditions.

Multi-body dynamics modelling of seated human body under exposure to whole-body vibration.

PubMed

Yoshimura, Takuya; Nakai, Kazuma; Tamaoki, Gen

2005-07-01

In vehicle systems occupational drivers might expose themselves to vibration for a long time. This may cause illness of the spine such as chronic lumbago or low back pain. Therefore, it is necessary to evaluate the influence of vibration to the spinal column and to make up appropriate guidelines or counter plans. In ISO2631-1 or ISO2631-5 assessment of vibration effects to human in the view of adverse-health effect was already presented. However, it is necessary to carry out further research to understand the effect of vibration to human body to examine their validity and to prepare for the future revision. This paper shows the detail measurement of human response to vibration, and the modelling of the seated human body for the assessment of the vibration risk. The vibration transmissibilities from the seat surface to the spinal column and to the head are measured during the exposure to vertical excitation. The modal paramters of seated subject are extracted in order to understand the dominant natural modes. For the evaluation of adverse-health effect the multi-body modelling of the spinal column is introduced. A simplified model having 10 DOFs is counstructed so that the transmissibilities of the model fit to those of experiment. The transient response analysis is illustrated when a half-sine input is applied. The relative displacements of vertebrae are evaluated, which can be a basis for the assessment of vibration risk. It is suggested that the multi-body dynamic model is used to evaluate the vibration effect to the spinal column for seated subjects.

Postoperative 3D spine reconstruction by navigating partitioning manifolds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kadoury, Samuel, E-mail: samuel.kadoury@polymtl.ca; Labelle, Hubert, E-mail: hubert.labelle@recherche-ste-justine.qc.ca; Parent, Stefan, E-mail: stefan.parent@umontreal.ca

Purpose: The postoperative evaluation of scoliosis patients undergoing corrective treatment is an important task to assess the strategy of the spinal surgery. Using accurate 3D geometric models of the patient’s spine is essential to measure longitudinal changes in the patient’s anatomy. On the other hand, reconstructing the spine in 3D from postoperative radiographs is a challenging problem due to the presence of instrumentation (metallic rods and screws) occluding vertebrae on the spine. Methods: This paper describes the reconstruction problem by searching for the optimal model within a manifold space of articulated spines learned from a training dataset of pathological casesmore » who underwent surgery. The manifold structure is implemented based on a multilevel manifold ensemble to structure the data, incorporating connections between nodes within a single manifold, in addition to connections between different multilevel manifolds, representing subregions with similar characteristics. Results: The reconstruction pipeline was evaluated on x-ray datasets from both preoperative patients and patients with spinal surgery. By comparing the method to ground-truth models, a 3D reconstruction accuracy of 2.24 ± 0.90 mm was obtained from 30 postoperative scoliotic patients, while handling patients with highly deformed spines. Conclusions: This paper illustrates how this manifold model can accurately identify similar spine models by navigating in the low-dimensional space, as well as computing nonlinear charts within local neighborhoods of the embedded space during the testing phase. This technique allows postoperative follow-ups of spinal surgery using personalized 3D spine models and assess surgical strategies for spinal deformities.« less

Mechanical hypersensitivity, sympathetic sprouting, and glial activation are attenuated by local injection of corticosteroid near the lumbar ganglion in a rat model of neuropathic pain.

PubMed

Li, Jing-Yi; Xie, Wenrui; Strong, Judith A; Guo, Qu-Lian; Zhang, Jun-Ming

2011-01-01

Inflammatory responses in the lumbar dorsal root ganglion (DRG) play a key role in pathologic pain states. Systemic administration of a common anti-inflammatory corticosteroid, triamcinolone acetonide (TA), reduces sympathetic sprouting, mechanical pain behavior, spontaneous bursting activity, and cytokine and nerve growth factor production in the DRG. We hypothesized that systemic TA effects are primarily due to local effects on the DRG. Male Sprague-Dawley rats were divided into 4 groups: SNL (tight ligation and transection of spinal nerves) and normal with and without a single dose of TA injectable suspension slowly injected onto the surface of DRG and surrounding region at the time of SNL or sham surgery. Mechanical threshold was tested on postoperative days 1, 3, 5, and 7. Immunohistochemical staining examined tyrosine hydroxylase and glial fibrillary acidic protein in DRG and CD11B antibody (OX-42) in spinal cord. Local TA treatment attenuated mechanical sensitivity, reduced sympathetic sprouting in the DRG, and decreased satellite glia activation in the DRG and microglia activation in the spinal cord after SNL. A single injection of corticosteroid in the vicinity of the axotomized DRG can mimic many effects of systemic TA, mitigating behavioral and cellular abnormalities induced by spinal nerve ligation. This provides a further rationale for the use of localized steroid injections clinically and provides further support for the idea that localized inflammation at the level of the DRG is an important component of the spinal nerve ligation model, commonly classified as neuropathic pain model.

Effective robotic assistive pattern of treadmill training for spinal cord injury in a rat model

PubMed Central

Zhao, Bo-Lun; Li, Wen-Tao; Zhou, Xiao-Hua; Wu, Su-Qian; Cao, Hong-Shi; Bao, Zhu-Ren; An, Li-Bin

2018-01-01

The purpose of the present study was to establish an effective robotic assistive stepping pattern of body-weight-supported treadmill training based on a rat spinal cord injury (SCI) model and assess the effect by comparing this with another frequently used assistive stepping pattern. The recorded stepping patterns of both hind limbs of trained intact rats were edited to establish a 30-sec playback normal rat stepping pattern (NRSP). Step features (step length, step height, step number and swing duration), BBB scores, latencies, and amplitudes of the transcranial electrical motor-evoked potentials (tceMEPs) and neurofilament 200 (NF200) expression in the spinal cord lesion area during and after 3 weeks of body-weight-supported treadmill training (BWSTT) were compared in rats with spinal contusion receiving NRSP assistance (NRSPA) and those that received manual assistance (MA). Hind limb stepping performance among rats receiving NRSPA during BWSTT was greater than that among rats receiving MA in terms of longer step length, taller step height, and longer swing duration. Furthermore a higher BBB score was also indicated. The rats in the NRSPA group achieved superior results in the tceMEPs assessment and greater NF200 expression in the spinal cord lesion area compared with the rats in the MA group. These findings suggest NRSPA was an effective assistive pattern of treadmill training compared with MA based on the rat SCI model and this approach could be used as a new platform for animal experiments for better understanding the mechanisms of SCI rehabilitation. PMID:29545846

Electro-acupuncture decreases 5-HT, CGRP and increases NPY in the brain-gut axis in two rat models of Diarrhea-predominant irritable bowel syndrome(D-IBS).

PubMed

Sun, Jianhua; Wu, Xiaoliang; Meng, Yunfang; Cheng, Jie; Ning, Houxu; Peng, Yongjun; Pei, Lixia; Zhang, Wei

2015-09-29

To examine whether electro-acupuncture (EA) could decrease 5-hydroxytryptamine (5-HT) and calcitonin gene-related peptide (CGRP), and increase neuro-peptide Y (NPY) in the brain-gut axis (BGA) in D-IBS using rat models. Rats were randomly exposed to unpredictable chronic stress for 3 weeks followed by 1-hour acute restraint stress (CAS) after 7 days of rest, or daily gavage of Senna decoction (6 g/kg) plus chronic restraint stress (for a duration of 2 h, starting from 1 h prior to the gavage) for 2 weeks (ISC). The content of 5-HT, CGRP and NPY in the distal colon, spinal cord, hypothalamus was examined at the end of the treatment. 1. The two rat models exhibited similar characteristics, e.g., increased number of fecal pellets expelled in 1 h, decreased sacchar-intake, decreased CRD, elevated 5-HT, CGRP content and decreased NPY in the distal colon, spinal cord, hypothalamus (P < 0.05 vs. that in healthy control rats). 2. A series of equations was developed based on correlation regression analysis. The analysis results demonstrated that 5-HT mediates the changes in hypothalamus, spinal cord and colon. 5-HT and CGRP in spinal cord was closely correlated with general behavior evaluation and other transmitters in BGA. 1. In comparison to 5-HT, CGRP and NPY (particularly in the spinal cord) had closer relationship with the D-IBS symptoms induced by either stress factors or Senna decotion. 2. EA treatment could restore the brain-gut axis to balanced levels.

Numb rats walk - a behavioural and fMRI comparison of mild and moderate spinal cord injury.

PubMed

Hofstetter, Christoph P; Schweinhardt, Petra; Klason, Tomas; Olson, Lars; Spenger, Christian

2003-12-01

Assessment of sensory function serves as a sensitive measure for predicting the functional outcome following spinal cord injury in patients. However, little is known about loss and recovery of sensory function in rodent spinal cord injury models as most tests of sensory functions rely on behaviour and thus motor function. We used functional magnetic resonance imaging (fMRI) to investigate cortical and thalamic BOLD-signal changes in response to limb stimulation following mild or moderate thoracic spinal cord weight drop injury in Sprague-Dawley rats. While there was recovery of close to normal hindlimb motor function as determined by open field locomotor testing following both degrees of injury, recovery of hindlimb sensory function as determined by fMRI and hot plate testing was only seen following mild injury and not following moderate injury. Thus, moderate injury can lead to near normal hindlimb motor function in animals with major sensory deficits. Recovered fMRI signals following mild injury had a partly altered cortical distribution engaging also ipsilateral somatosensory cortex and the cingulate gyrus. Importantly, thoracic spinal cord injury also affected sensory representation of the upper nonaffected limbs. Thus, cortical and thalamic activation in response to forelimb stimulation was significantly increased 16 weeks after spinal cord injury compared to control animals. We conclude that both forelimb and hindlimb cortical sensory representation is altered following thoracic spinal cord injury. Furthermore tests of sensory function that are independent of motor behaviour are needed in rodent spinal cord injury research.

Compression and contact area of anterior strut grafts in spinal instrumentation: a biomechanical study.

PubMed

Pizanis, Antonius; Holstein, Jörg H; Vossen, Felix; Burkhardt, Markus; Pohlemann, Tim

2013-08-26

Anterior bone grafts are used as struts to reconstruct the anterior column of the spine in kyphosis or following injury. An incomplete fusion can lead to later correction losses and compromise further healing. Despite the different stabilizing techniques that have evolved, from posterior or anterior fixating implants to combined anterior/posterior instrumentation, graft pseudarthrosis rates remain an important concern. Furthermore, the need for additional anterior implant fixation is still controversial. In this bench-top study, we focused on the graft-bone interface under various conditions, using two simulated spinal injury models and common surgical fixation techniques to investigate the effect of implant-mediated compression and contact on the anterior graft. Calf spines were stabilised with posterior internal fixators. The wooden blocks as substitutes for strut grafts were impacted using a "pressfit" technique and pressure-sensitive films placed at the interface between the vertebral bone and the graft to record the compression force and the contact area with various stabilization techniques. Compression was achieved either with posterior internal fixator alone or with an additional anterior implant. The importance of concomitant ligament damage was also considered using two simulated injury models: pure compression Magerl/AO fracture type A or rotation/translation fracture type C models. In type A injury models, 1 mm-oversized grafts for impaction grafting provided good compression and fair contact areas that were both markedly increased by the use of additional compressing anterior rods or by shortening the posterior fixator construct. Anterior instrumentation by itself had similar effects. For type C injuries, dramatic differences were observed between the techniques, as there was a net decrease in compression and an inadequate contact on the graft occurred in this model. Under these circumstances, both compression and the contact area on graft could only be maintained at high levels with the use of additional anterior rods. Under experimental conditions, we observed that ligamentous injury following type C fracture has a negative influence on the compression and contact area of anterior interbody bone grafts when only an internal fixator is used for stabilization. Because of the loss of tension banding effects in type C injuries, an additional anterior compressing implant can be beneficial to restore both compression to and contact on the strut graft.

Clinical interpretation of the Spinal Cord Injury Functional Index (SCI-FI)

PubMed Central

Fyffe, Denise; Kalpakjian, Claire Z.; Slavin, Mary; Kisala, Pamela; Ni, Pengsheng; Kirshblum, Steven C.; Tulsky, David S.; Jette, Alan M.

2016-01-01

Objective: To provide validation of functional ability levels for the Spinal Cord Injury – Functional Index (SCI-FI). Design: Cross-sectional. Setting: Inpatient rehabilitation hospital and community settings. Participants: A sample of 855 individuals with traumatic spinal cord injury enrolled in 6 rehabilitation centers participating in the National Spinal Cord Injury Model Systems Network. Interventions: Not Applicable. Main Outcome Measures: Spinal Cord Injury-Functional Index (SCI-FI). Results: Cluster analyses identified three distinct groups that represent low, mid-range and high SCI-FI functional ability levels. Comparison of clusters on personal and other injury characteristics suggested some significant differences between groups. Conclusions: These results strongly support the use of SCI-FI functional ability levels to document the perceived functional abilities of persons with SCI. Results of the cluster analysis suggest that the SCI-FI functional ability levels capture function by injury characteristics. Clinical implications regarding tracking functional activity trajectories during follow-up visits are discussed. PMID:26781769

Mechanosensory neurons control the timing of spinal microcircuit selection during locomotion

PubMed Central

Knafo, Steven; Fidelin, Kevin; Prendergast, Andrew; Tseng, Po-En Brian; Parrin, Alexandre; Dickey, Charles; Böhm, Urs Lucas; Figueiredo, Sophie Nunes; Thouvenin, Olivier; Pascal-Moussellard, Hugues; Wyart, Claire

2017-01-01

Despite numerous physiological studies about reflexes in the spinal cord, the contribution of mechanosensory feedback to active locomotion and the nature of underlying spinal circuits remains elusive. Here we investigate how mechanosensory feedback shapes active locomotion in a genetic model organism exhibiting simple locomotion—the zebrafish larva. We show that mechanosensory feedback enhances the recruitment of motor pools during active locomotion. Furthermore, we demonstrate that inputs from mechanosensory neurons increase locomotor speed by prolonging fast swimming at the expense of slow swimming during stereotyped acoustic escape responses. This effect could be mediated by distinct mechanosensory neurons. In the spinal cord, we show that connections compatible with monosynaptic inputs from mechanosensory Rohon-Beard neurons onto ipsilateral V2a interneurons selectively recruited at high speed can contribute to the observed enhancement of speed. Altogether, our study reveals the basic principles and a circuit diagram enabling speed modulation by mechanosensory feedback in the vertebrate spinal cord. DOI: http://dx.doi.org/10.7554/eLife.25260.001 PMID:28623664

[Expression and significance of p75NTR in dorsal root ganglia in different injury models].

PubMed

Li, Fang; Cai, Yan; Zhang, Jian-Yi

2008-12-01

To determine the expression and significance of p75NTR in the neuron and glia of dorsal root ganglia (DRG) in different injury models. The models of sciatic nerve injury, spinal cord injury, and combined injury (sciatic nerve injury one week prior to spinal cord injury) were established. The rats were randomly divided into a normal group,a sciatic nerve injury group,a spinal cord injury group, and a combined injury group. The sensory neurons in the DRG were labeled by fast blue (FB) injected in the dorsal column of spinal cord 0.5mm rostral to the transection site. The expression of p75NTR in the neurons and glia of the DRG was examined with immunofluorescence histochemistry after different kinds of injury and its expression in the FB positive neurons was further observed with immunofluorescence histochemistry combined with FB retrograde labeling. The expression of p75NTR was increased in the glia, but was downregulated in sensory neurons in the sciatic nerve injury group compared with the normal group. p75NTR immunoreactive products were downregulated in the glia in the spinal cord injury group compared with the sciatic nerve injury group or the combined injury group. In the combined lesion animals, the expression of p75NTR was similar to that of the sciatic nerve injury group. Its expression in the sensory neurons of DRG was downregulated,but was upregulated in the glia. The majority of sensory neurons labeled by FB in the combined injury group were p75NTR-negative, but surrounded by p75NTR-positive glia. p75NTR immunoreactive products in the glia and neurons of DRG have significant discrepancy after injury. The glial p75NTR in the DRG may play a role in the enhanced regeneration of acsending tract in the injured spinal cord after combined injury.

Human neural progenitors differentiate into astrocytes and protect motor neurons in aging rats.

PubMed

Das, Melanie M; Avalos, Pablo; Suezaki, Patrick; Godoy, Marlesa; Garcia, Leslie; Chang, Christine D; Vit, Jean-Philippe; Shelley, Brandon; Gowing, Genevieve; Svendsen, Clive N

2016-06-01

Age-associated health decline presents a significant challenge to healthcare, although there are few animal models that can be used to test potential treatments. Here, we show that there is a significant reduction in both spinal cord motor neurons and motor function over time in the aging rat. One explanation for this motor neuron loss could be reduced support from surrounding aging astrocytes. Indeed, we have previously shown using in vitro models that aging rat astrocytes are less supportive to rat motor neuron function and survival over time. Here, we test whether rejuvenating the astrocyte niche can improve the survival of motor neurons in an aging spinal cord. We transplanted fetal-derived human neural progenitor cells (hNPCs) into the aging rat spinal cord and found that the cells survive and differentiate into astrocytes with a much higher efficiency than when transplanted into younger animals, suggesting that the aging environment stimulates astrocyte maturation. Importantly, the engrafted astrocytes were able to protect against motor neuron loss associated with aging, although this did not result in an increase in motor function based on behavioral assays. We also transplanted hNPCs genetically modified to secrete glial cell line-derived neurotrophic factor (GDNF) into the aging rat spinal cord, as this combination of cell and protein delivery can protect motor neurons in animal models of ALS. During aging, GDNF-expressing hNPCs protected motor neurons, though to the same extent as hNPCs alone, and again had no effect on motor function. We conclude that hNPCs can survive well in the aging spinal cord, protect motor neurons and mature faster into astrocytes when compared to transplantation into the young spinal cord. While there was no functional improvement, there were no functional deficits either, further supporting a good safety profile of hNPC transplantation even into the older patient population. Copyright © 2016 Elsevier Inc. All rights reserved.

Co-induction of the heat shock response ameliorates disease progression in a mouse model of human spinal and bulbar muscular atrophy: implications for therapy

PubMed Central

Malik, Bilal; Nirmalananthan, Niranjanan; Gray, Anna L.; La Spada, Albert R.; Hanna, Michael G.

2013-01-01

Spinal and bulbar muscular atrophy, also known as Kennedy’s disease, is an adult-onset hereditary neurodegenerative disorder caused by an expansion of the polyglutamine repeat in the first exon in the androgen receptor gene. Pathologically, the disease is defined by selective loss of spinal and bulbar motor neurons causing bulbar, facial and limb weakness. Although the precise disease pathophysiology is largely unknown, it appears to be related to abnormal accumulation of the pathogenic androgen receptor protein within the nucleus, leading to disruption of cellular processes. Using a mouse model of spinal and bulbar muscular atrophy that exhibits many of the characteristic features of the human disease, in vivo physiological assessment of muscle function revealed that mice with the pathogenic expansion of the androgen receptor develop a motor deficit characterized by a reduction in muscle force, abnormal muscle contractile characteristics, loss of functional motor units and motor neuron degeneration. We have previously shown that treatment with arimoclomol, a co-inducer of the heat shock stress response, delays disease progression in the mutant superoxide dismutase 1 mouse model of amyotrophic lateral sclerosis, a fatal motor neuron disease. We therefore evaluated the therapeutic potential of arimoclomol in mice with spinal and bulbar muscular atrophy. Arimoclomol was administered orally, in drinking water, from symptom onset and the effects established at 18 months of age, a late stage of disease. Arimoclomol significantly improved hindlimb muscle force and contractile characteristics, rescued motor units and, importantly, improved motor neuron survival and upregulated the expression of the vascular endothelial growth factor which possess neurotrophic activity. These results provide evidence that upregulation of the heat shock response by treatment with arimoclomol may have therapeutic potential in the treatment of spinal and bulbar muscular atrophy and may also be a possible approach for the treatment of other neurodegenerative diseases. PMID:23393146

Opioids delay healing of spinal fusion: a rabbit posterolateral lumbar fusion model.

PubMed

Jain, Nikhil; Himed, Khaled; Toth, Jeffrey M; Briley, Karen C; Phillips, Frank M; Khan, Safdar N

2018-04-19

Opioid use is prevalent for management of pre- and post-operative pain in patients undergoing spinal fusion. There is evidence that opioids downregulate osteoblasts in-vitro, and one previous study found that morphine delays the maturation and remodeling of callus in a rat femur fracture model. However, the effect of opioids on healing of spinal fusion has not been investigated before. Isolating the effect of opioid exposure in humans would be limited by the numerous confounding factors that affect fusion healing. Therefore, we have used a well-established rabbit model to study the process of spinal fusion healing that closely mimics humans. To study the effect of systemic opioids on the process of healing of spinal fusion in a rabbit posterolateral spinal fusion model. Pre-clinical animal study. 24 adult New Zealand white rabbits were studied in two groups after approval from the Institutional Animal Care and Use Committee (IACUC). The opioid group (n=12) received four-weeks pre-operative and six-weeks post-operative transdermal fentanyl. Serum fentanyl levels were measured just before surgery and four-weeks post-operatively to ensure adequate levels. The control group (n=12) received only peri-operative pain control as necessary. All animals received a bilateral L5-L6 posterolateral spinal fusion using iliac crest autograft. Animals were euthanized at the six-week post-operative time point, and assessment of fusion was done by manual palpation, plain radiographs, micro-computed tomography (microCT), and histology. 12 animals in control group and 11 animals in the opioid group were available for analysis at the end of six weeks. The fusion scores on manual palpation, radiographs, and microCT were not statistically different. Three-dimensional microCT morphometry found that the fusion mass in the opioid group had a lower bone volume (p=0.09), lower trabecular number (p=0.02) and higher trabecular separation (p=0.02) as compared to control. Histological analysis found areas of incorporation of autograft, and unincorporated graft fragments in both groups. In the control group, there was remodeling of de-novo woven bone to lamellar organization with incorporation of osteocytes, formation of mature marrow, and relative paucity of hypertrophied osteoblasts lining new bone. Sections from the opioid group showed formation of de-novo woven bone, and hypertrophied osteoblasts seen lining the new bone. There were no sections showing lamellar organization and development of mature marrow elements in the opioid group. Less dense trabeculae on microCT correlated with histological findings of relatively immature fusion mass in the opioid group. Systemic opioids led to an inferior quality fusion mass with delay in maturation and remodeling at six-weeks in this rabbit spinal fusion model. These preliminary results lay foundation for further research to investigate underlying cellular mechanisms, temporal fusion process, and dose-duration relationship of opioids responsible for our findings. Copyright © 2018 Elsevier Inc. All rights reserved.

SU-C-17A-07: The Development of An MR Accelerator-Enabled Planning-To-Delivery Technique for Stereotactic Palliative Radiotherapy Treatment of Spinal Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoogcarspel, S J; Kontaxis, C; Velden, J M van der

2014-06-01

Purpose: To develop an MR accelerator-enabled online planning-todelivery technique for stereotactic palliative radiotherapy treatment of spinal metastases. The technical challenges include; automated stereotactic treatment planning, online MR-based dose calculation and MR guidance during treatment. Methods: Using the CT data of 20 patients previously treated at our institution, a class solution for automated treatment planning for spinal bone metastases was created. For accurate dose simulation right before treatment, we fused geometrically correct online MR data with pretreatment CT data of the target volume (TV). For target tracking during treatment, a dynamic T2-weighted TSE MR sequence was developed. An in house developedmore » GPU based IMRT optimization and dose calculation algorithm was used for fast treatment planning and simulation. An automatically generated treatment plan developed with this treatment planning system was irradiated on a clinical 6 MV linear accelerator and evaluated using a Delta4 dosimeter. Results: The automated treatment planning method yielded clinically viable plans for all patients. The MR-CT fusion based dose calculation accuracy was within 2% as compared to calculations performed with original CT data. The dynamic T2-weighted TSE MR Sequence was able to provide an update of the anatomical location of the TV every 10 seconds. Dose calculation and optimization of the automatically generated treatment plans using only one GPU took on average 8 minutes. The Delta4 measurement of the irradiated plan agreed with the dose calculation with a 3%/3mm gamma pass rate of 86.4%. Conclusions: The development of an MR accelerator-enabled planning-todelivery technique for stereotactic palliative radiotherapy treatment of spinal metastases was presented. Future work will involve developing an intrafraction motion adaptation strategy, MR-only dose calculation, radiotherapy quality-assurance in a magnetic field, and streamlining the entire treatment process on an MR accelerator.« less

The effect of void creation prior to vertebroplasty on intravertebral pressure and cement distribution in cadaveric spines with simulated metastases.

PubMed

Li, Ka; Yan, Jun; Yang, Qiang; Li, Zhenfeng; Li, Jianmin

2015-01-28

For osteoporosis or spinal metastases, percutaneous vertebroplasty is effective in pain relief and improvement of mobility. However, the complication rate (cement extravasation and fat embolisms) is relatively higher in the treatment of spinal metastases. The presence of tumor tissue plays a significant role in intravertebral pressure and cement distribution and thereby affects the occurrence of complications. We investigated the effect of void creation prior to vertebroplasty on intravertebral pressure and cement distribution in spinal metastases. Eighteen vertebrae (T8-L4) from five cadaveric spines were randomly allocated for two groups (group with and without void) of nine vertebrae each. Defect was created by removing a central core of cancellous bone in the vertebral body and then filling it with 30% or 100% fresh muscle paste by volume to simulate void creation or no void creation, respectively. Then, 20% bone cement by volume of the vertebral body was injected into each specimen through a unipedicular approach at a rate of 3 mL/min. The gender of the donor, vertebral body size, bone density, cement volume, and intravertebral pressure were recorded. Then, computed tomography scans and cross sections were taken to evaluate the cement distribution in vertebral bodies. No significant difference was found between the two groups in terms of the gender of the donor, vertebral body size, bone density, or bone cement volume. The average maximum intravertebral pressure in the group with void creation was significantly lower than that in the group without void creation (1.20 versus 5.09 kPa, P = 0.001). Especially during the filling of void, the difference was more pronounced. Void creation prior to vertebroplasty allowed the bone cement to infiltrate into the lytic defect. In vertebroplasty for spinal metastases, void creation produced lower intravertebral pressure and facilitated cement filling. To reduce the occurrence of complication, it may be an alternative to eliminate the tumor tissue to create a void prior to cement injection.

Spinal pain and co-occurrence with stress and general well-being among young adolescents: a study within the Danish National Birth Cohort.

PubMed

Stallknecht, Sandra Elkjær; Strandberg-Larsen, Katrine; Hestbæk, Lise; Andersen, Anne-Marie Nybo

2017-06-01

This study aims to describe the patterns in low back, mid back, and neck pain complaints in young adolescents from the Danish National Birth Cohort (DNBC) and to investigate the co-occurrence of spinal pain and stress and general well-being, respectively. Cross-sectional data from the 11-year follow-up of DNBC were used. As part of a web-based survey, a total of 45,371 young adolescents between 10 and 14 years old completed the Young Spine Questionnaire, the Stress in Children Questionnaire, and a one-item question on general well-being. Associations between spinal pain and, respectively, stress and general well-being were estimated by means of multiple logistic regression models. Almost one fifth of boys and one quarter of girls reported spinal pain. Compared with adolescents who reported no stress, adolescents reporting medium and high values of stress had odds ratios (OR) of 2.19 (95% CI 2.08-2.30) and 4.73 (95% CI 4.28-5.23), respectively, of reporting spinal pain (adjusted for age, gender, and maternal education). Adolescents who reported poor general well-being had an OR of 2.50 (95% CI 2.31-2.72) for reporting spinal pain compared to adolescents with good general well-being. Spinal pain is a common complaint among young adolescents and co-occurs with stress and poor general well-being. The mutual dependency between the factors remained to be explained. What is Known: • The prevalence of spinal pain increases rapidly during childhood and adolescence, but different measurement instruments result in great variation in the estimates of spinal pain in children and adolescents. • Some studies have shown that different psychosocial measures are associated with spinal pain in children and adolescents. What is New: • Spinal pain, as measured by the newly developed and validated Young Spine Questionnaire, is a common complaint in young adolescents aged 10-14 years. • Spinal pain in young adolescents co-occurs with stress and poor general well-being.

Impact of spinal pain on daily living activities in postmenopausal women working in agriculture.

PubMed

Raczkiewicz, Dorota; Owoc, Alfred; Sarecka-Hujar, Beata; Saran, Tomasz; Bojar, Iwona

2017-03-22

Postmenopausal women working in agriculture suffer from spinal pain for two overlapping reasons, the first is related to the menopause and the second to the specificity of rural work, which includes lifting heavy objects and changing weather conditions. Spinal pain affects the daily life of women as well as their ability to work. The objective of the study was to analyse the impact of spinal pain on activities of daily life in Polish postmenopausal women performing agricultural work. The study was conducted in 2016 in Poland and included 1,119 post-menopausal women living in rural areas and working in agriculture. The women assessed the severity of spinal pain in 3 sections: neck, thorax and lumbar. Neck Disability Index (NDI) and Oswestry Low Back Disability Index (ODI) questionnaires were used to assess the impact of spinal pain on daily life activities. Generalized linear models were estimated in statistical analyses. Postmenopausal women working in agriculture suffered most often from pain in the lumbar spine, less frequently in the neck, and the least in the thoracic. The most common was an isolated pain in only one section of the spine. Spinal pain disturbed the most the women's rest, standing, lifting objects, while sleep, concentration, and walking the least. The impact of spinal pain on the activities of daily life, on average, was moderate, and increased with greater pain severity, the earlier the age the pain started, the higher the body weight, the lower education level and if there was a co-existing pain in any of the other spine sections. The impact of spinal pain on daily life activities did not depend on age between 45-65, WHR, age at last menstruation, parity, and number and types of births. The impact of spinal pain on daily life activities in postmenopausal women working in agriculture was assessed as moderate, on average, and depended mainly on spinal pain-related characteristics, such as severity, age at onset and co-existence of pain in any other spinal sections.

In vitro biomechanical comparison after fixed- and mobile-core artificial cervical disc replacement versus fusion

PubMed Central

Lou, Jigang; Li, Yuanchao; Wang, Beiyu; Meng, Yang; Wu, Tingkui; Liu, Hao

2017-01-01

Abstract In vitro biomechanical analysis after cervical disc replacement (CDR) with a novel artificial disc prosthesis (mobile core) was conducted and compared with the intact model, simulated fusion, and CDR with a fixed-core prosthesis. The purpose of this experimental study was to analyze the biomechanical changes after CDR with a novel prosthesis and the differences between fixed- and mobile-core prostheses. Six human cadaveric C2–C7 specimens were biomechanically tested sequentially in 4 different spinal models: intact specimens, simulated fusion, CDR with a fixed-core prosthesis (Discover, DePuy), and CDR with a mobile-core prosthesis (Pretic-I, Trauson). Moments up to 2 Nm with a 75 N follower load were applied in flexion–extension, left and right lateral bending, and left and right axial rotation. The total range of motion (ROM), segmental ROM, and adjacent intradiscal pressure (IDP) were calculated and analyzed in 4 different spinal models, as well as the differences between 2 disc prostheses. Compared with the intact specimens, the total ROM, segmental ROM, and IDP at the adjacent segments showed no significant difference after arthroplasty. Moreover, CDR with a mobile-core prosthesis presented a little higher values of target segment (C5/6) and total ROM than CDR with a fixed-core prosthesis (P > .05). Besides, the difference in IDP at C4/5 after CDR with 2 prostheses was without statistical significance in all the directions of motion. However, the IDP at C6/7 after CDR with a mobile-core prosthesis was lower than CDR with a fixed-core prosthesis in flexion, extension, and lateral bending, with significant difference (P < .05), but not under axial rotation. CDR with a novel prosthesis was effective to maintain the ROM at the target segment and did not affect the ROM and IDP at the adjacent segments. Moreover, CDR with a mobile-core prosthesis presented a little higher values of target segment and total ROM, but lower IDP at the inferior adjacent segment than CDR with a fixed-core prosthesis. PMID:29019902

Gene Transfer of Glutamic Acid Decarboxylase 67 by Herpes Simplex Virus Vectors Suppresses Neuropathic Pain Induced by Human Immunodeficiency Virus gp120 Combined with ddC in Rats.

PubMed

Kanao, Megumi; Kanda, Hirotsugu; Huang, Wan; Liu, Shue; Yi, Hyun; Candiotti, Keith A; Lubarsky, David A; Levitt, Roy C; Hao, Shuanglin

2015-06-01

Human immunodeficiency virus (HIV)-related painful sensory neuropathies primarily consist of the HIV infection-related distal sensory polyneuropathy and antiretroviral toxic neuropathies. Pharmacotherapy provides only partial relief of pain in patients with HIV/acquired immune deficiency syndrome because little is known about the exact neuropathological mechanisms for HIV-associated neuropathic pain (NP). Hypofunction of γ-aminobutyric acid (GABA) GABAergic inhibitory mechanisms has been reported after peripheral nerve injury. In this study, we tested the hypothesis that HIV gp120 combined with antiretroviral therapy reduces spinal GABAergic inhibitory tone and that restoration of GABAergic inhibitory tone will reduce HIV-related NP in a rat model. The application of recombinant HIV-1 envelope protein gp120 into the sciatic nerve plus systemic ddC (one antiretroviral drug) induced mechanical allodynia. The hind paws of rats were inoculated with replication-defective herpes simplex virus (HSV) vectors genetically encoding gad1 gene to express glutamic acid decarboxylase 67 (GAD67), an enzyme that catalyzes the decarboxylation of glutamate to GABA. Mechanical threshold was tested using von Frey filaments before and after treatments with the vectors. The expression of GAD67 in both the lumbar spinal cord and the L4-5 dorsal root ganglia was examined using western blots. The expression of mitochondrial superoxide in the spinal dorsal horn was examined using MitoSox imaging. The immunoreactivity of spinal GABA, pCREB, and pC/EBPβ was tested using immunohistochemistry. In the gp120 with ddC-induced neuropathic pain model, GAD67 expression mediated by the HSV vector caused an elevation of mechanical threshold that was apparent on day 3 after vector inoculation. The antiallodynic effect of the single HSV vector inoculation expressing GAD67 lasted >28 days. The area under the time-effect curves in the HSV vector expressing GAD67 was increased compared with that in the control vectors (P = 0.0005). Intrathecal GABA-A/B agonists elevated mechanical threshold in the pain model. The HSV vectors expressing GAD67 reversed the lowered GABA immunoreactivity in the spinal dorsal horn in the neuropathic rats. HSV vectors expressing GAD67 in the neuropathic rats reversed the increased signals of mitochondrial superoxide in the spinal dorsal horn. The vectors expressing GAD67 reversed the upregulated immunoreactivity expression of pCREB and pC/EBPβ in the spinal dorsal horn in rats exhibiting NP. Based on our results, we suggest that GAD67 mediated by HSV vectors acting through the suppression of mitochondrial reactive oxygen species and transcriptional factors in the spinal cord decreases pain in the HIV-related neuropathic pain model, providing preclinical evidence for gene therapy applications in patients with HIV-related pain states.

Dynamic membrane depolarization is an early regulator of ependymoglial cell response to spinal cord injury in axolotl

PubMed Central

Sabin, Keith; Santos-Ferreira, Tiago; Essig, Jaclyn; Rudasill, Sarah; Echeverri, Karen

2016-01-01

Salamanders, such as the Mexican axolotl, are some of the few vertebrates fortunate in their ability to regenerate diverse structures after injury. Unlike mammals they are able to regenerate a fully functional spinal cord after injury. However, the molecular circuitry required to initiate a pro-regenerative response after spinal cord injury is not well understood. To address this question we developed a spinal cord injury model in axolotls and used in vivo imaging of labeled ependymoglial cells to characterize the response of these cells to injury. Using in vivo imaging of ion sensitive dyes we identified that spinal cord injury induces a rapid and dynamic change in the resting membrane potential of ependymoglial cells. Prolonged depolarization of ependymoglial cells after injury inhibits ependymoglial cell proliferation and subsequent axon regeneration. Using transcriptional profiling we identified c-Fos as a key voltage sensitive early response gene that is expressed specifically in the ependymoglial cells after injury. This data establishes that dynamic changes in the membrane potential after injury are essential for regulating the specific spatiotemporal expression of c-Fos that is critical for promoting faithful spinal cord regeneration in axolotl. PMID:26477559

Spasticity therapy reacts to astrocyte GluA1 receptor upregulation following spinal cord injury

PubMed Central

Gómez-Soriano, Julio; Goiriena, Eider; Taylor, Julian

2010-01-01

For almost three decades intrathecal baclofen therapy has been the standard treatment for spinal cord injury spasticity when oral medication is ineffective or produces serious side effects. Although intrathecal baclofen therapy has a good clinical benefit-risk ratio for spinal spasticity, tolerance and the life-threatening withdrawal syndrome present serious problems for its management. Now, in an experimental model of spinal cord injury spasticity, AMPA receptor blockade with NGX424 (Tezampanel) has been shown to reduce stretch reflex activity alone and during tolerance to intrathecal baclofen therapy. These results stem from the observation that GluA1 receptors are overexpressed on reactive astrocytes following experimental ischaemic spinal cord injury. Although further validation is required, the appropriate choice of AMPA receptor antagonists for treatment of stretch hyperreflexia based on our recent understanding of reactive astrocyte neurobiology following spinal cord injury may lead to the development of a better adjunct clinical therapy for spasticity without the side effects of intrathecal baclofen therapy. LINKED ARTICLE This article is a commentary on Oshiro et al., pp. 976–985 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2010.00954.x PMID:20662840

WISE 2005: Aerobic and resistive countermeasures prevent paraspinal muscle deconditioning during 60-day bed rest in women.

PubMed

Holt, Jacquelyn A; Macias, Brandon R; Schneider, Suzanne M; Watenpaugh, Donald E; Lee, Stuart M C; Chang, Douglas G; Hargens, Alan R

2016-05-15

Microgravity-induced lumbar paraspinal muscle deconditioning may contribute to back pain commonly experienced by astronauts and may increase the risk of postflight injury. We hypothesized that a combined resistive and aerobic exercise countermeasure protocol that included spinal loading would mitigate lumbar paraspinal muscle deconditioning during 60 days of bed rest in women. Sixteen women underwent 60-day, 6° head-down-tilt bed rest (BR) and were randomized into control and exercise groups. During bed rest the control group performed no exercise. The exercise group performed supine treadmill exercise within lower body negative pressure (LBNP) for 3-4 days/wk and flywheel resistive exercise for 2-3 days/wk. Paraspinal muscle cross-sectional area (CSA) was measured using a lumbar spine MRI sequence before and after BR. In addition, isokinetic spinal flexion and extension strengths were measured before and after BR. Data are presented as means ± SD. Total lumbar paraspinal muscle CSA decreased significantly more in controls (10.9 ± 3.4%) than in exercisers (4.3 ± 3.4%; P < 0.05). The erector spinae was the primary contributor (76%) to total lumbar paraspinal muscle loss. Moreover, exercise attenuated isokinetic spinal extension loss (-4.3 ± 4.5%), compared with controls (-16.6 ± 11.2%; P < 0.05). In conclusion, LBNP treadmill and flywheel resistive exercises during simulated microgravity mitigate decrements in lumbar paraspinal muscle structure and spine function. Therefore spaceflight exercise countermeasures that attempt to reproduce spinal loads experienced on Earth may mitigate spinal deconditioning during long-duration space travel.

A Novel Spinal Implant for Fusionless Scoliosis Correction: A Biomechanical Analysis of the Motion Preserving Properties of a Posterior Periapical Concave Distraction Device

PubMed Central

Holewijn, Roderick M.; de Kleuver, Marinus; van der Veen, Albert J.; Emanuel, Kaj S.; Bisschop, Arno; Stadhouder, Agnita; van Royen, Barend J.

2017-01-01

Study Design: Biomechanical study. Objective: Recently, a posterior concave periapical distraction device for fusionless scoliosis correction was introduced. The goal of this study was to quantify the effect of the periapical distraction device on spinal range of motion (ROM) in comparison with traditional rigid pedicle screw-rod instrumentation. Methods: Using a spinal motion simulator, 6 human spines were loaded with 4 N m and 6 porcine spines with 2 N m to induce flexion-extension (FE), lateral bending (LB), and axial rotation (AR). ROM was measured in 3 conditions: untreated, periapical distraction device, and rigid pedicle screw-rod instrumentation. Results: The periapical distraction device caused a significant (P < .05) decrease in ROM of FE (human, −40.0% and porcine, −55.9%) and LB (human, −18.2% and porcine, −17.9%) as compared to the untreated spine, while ROM of AR remained unaffected. In comparison, rigid instrumentation caused a significantly (P < .05) larger decrease in ROM of FE (human, −80.9% and porcine, −94.0%), LB (human, −75.0% and porcine, −92.2%), and AR (human, −71.3% and porcine, −86.9%). Conclusions: Although no destructive forces were applied, no device failures were observed. Spinal ROM was significantly less constrained by the periapical distraction device compared to rigid pedicle screw-rod instrumentation. Therefore, provided that scoliosis correction is achieved, a more physiological spinal motion is expected after scoliosis correction with the posterior concave periapical distraction device. PMID:28811983

Modulation of the neurological and vascular complications by grape seed extract in a rat model of spinal cord ischemia-reperfusion injury by downregulation of both osteopontin and cyclooxygenase-2.

PubMed

Sakr, Hussein F; Abbas, Amr M; Bin-Jaliah, Ismaeel

2016-07-01

In this study, we investigated the effects of grape seed extract (GSE) on the expression of osteopontin (OPN) and cyclooxygenase-2 (COX-2) in a rat model of spinal cord ischemia-reperfusion injury (SC-IRI). Fifty male rats were divided into 5 groups: control (CON); control + GSE (CON + GSE) (received GSE for 28 days); sham operated (Sham); IRI; and IRI + GSE. SC-IRI was induced by clamping the aorta just above the bifurcation for 45 min, and then the clamp was released for 48 h for reperfusion. IRI + GSE group received GSE for 28 days before SC-IRI. Sensory, motor, and placing/stepping reflex assessment was performed. Prostaglandin E2 (PGE2), thiobarbituric acid reactive substances (TBARs), and total antioxidant capacity (TAC) were measured in spinal cord homogenate. Immunohistochemical examination of the spinal cord for OPN and COX-2 were carried out. SC-IRI resulted in significant increase in plasma nitrite/nitrate level and spinal cord homogenate levels of TBARs and PGE2, and OPN and COX-2 expression with significant decrease in TAC. GSE improves the sensory and motor functions through decreasing OPN and COX-2 expression with reduction of oxidative stress parameters. We conclude a neuroprotective effect of GSE in SC-IRI through downregulating COX-2 and OPN expression plus its antioxidants effects.

[Effect of jingui shenqi pill on morphology of injured spinal cell apoptosis in rats caused by brachytherapy].

PubMed

Xiao, Lu-wei; Shen, Jin-wen; Wu, Cheng-liang

2006-07-01

To study the effect of Jingui Shenqi Pill (JSP) on morphology of spinal cell apoptosis in rats injured by 192Ir irradiation. One hundred and twenty rats were randomly divided into four groups: the model group, the JSP group, the prednisone group and the normal group. Corresponding pharmaceutics were given to rats once a day for 14 days respectively. Then except rats in the normal group, the others received 192Ir interstitial irradiation with the dosage of 22 Gy using back-fixing technology. The injured segments of spinal cord were taken out for HE staining, TUNEL examination and observation with electron microscope 8 hrs, 24 hrs and 4 weeks after irradiation. HE staining examination showed no obvious histological change in rats 8 and 24 hrs after irradiation, but pathological changes, as tissue rarefaction and hemorrhage did found in white matter of spinal cord shown by TUNEL 4 weeks later. Electron microscopic examination and TUNEL staining showed that as compared with the model group, the apoptotic index in the JSP and predinisone treated groups was significantly lower (P < 0.01) 8 hrs after radiation, but it showed insignificant difference between groups at the time points of 24 hrs and 4 weeks after radiation (P > 0.05). JSP could act against apoptosis of gliocyte in spinal cord of rats in early stage after brachytherapy, indicating that JSP possessing a prednisone-like action.

Mu-Opioid Receptors in Ganglia, But Not in Muscle, Mediate Peripheral Analgesia in Rat Muscle Pain.

PubMed

Bagues, Ana; Martín, María Isabel; Higuera-Matas, Alejandro; Esteban-Hernández, Jesús; Ambrosio, Emilio; Sánchez-Robles, Eva María

2018-04-01

Previous studies have demonstrated the participation of peripheral μ-opioid receptors (MOR) in the antinociceptive effect of systemically administered morphine and loperamide in an orofacial muscle pain model, induced by hypertonic saline, but not in a spinally innervated one, in rats. In this study, we determine whether this peripheral antinociceptive effect is due to the activation of MOR localized in the muscle, ganglia, or both. To determine the local antinociceptive effect of morphine and loperamide, 2 models of acute muscle pain (trigeminal and spinal) were used. Also, to study the MOR expression, protein quantification was performed in the trigeminal and spinal ganglia, and in the muscles. The behavioral results show that the intramuscular injection of morphine and loperamide did not exert an antinociceptive effect in either muscle (morphine: P = .63, loperamide: P = .9). On the other hand, MOR expression was found in the ganglia but not in the muscles. This expression was on average 44% higher (95% confidence interval, 33.3-53.9) in the trigeminal ganglia than in the spinal one. The peripheral antinociceptive effect of systemically administered opioids may be due to the activation of MOR in ganglia. The greater expression of MOR in trigeminal ganglia could explain the higher antinociceptive effect of opioids in orofacial muscle pain than in spinal muscle pain. Therefore, peripheral opioids could represent a promising approach for the treatment of orofacial pain.

Early and progressive impairment of spinal blood flow-glucose metabolism coupling in motor neuron degeneration of ALS model mice.

PubMed

Miyazaki, Kazunori; Masamoto, Kazuto; Morimoto, Nobutoshi; Kurata, Tomoko; Mimoto, Takahumi; Obata, Takayuki; Kanno, Iwao; Abe, Koji

2012-03-01

The exact mechanism of selective motor neuron death in amyotrophic lateral sclerosis (ALS) remains still unclear. In the present study, we performed in vivo capillary imaging, directly measured spinal blood flow (SBF) and glucose metabolism, and analyzed whether if a possible flow-metabolism coupling is disturbed in motor neuron degeneration of ALS model mice. In vivo capillary imaging showed progressive decrease of capillary diameter, capillary density, and red blood cell speed during the disease course. Spinal blood flow was progressively decreased in the anterior gray matter (GM) from presymptomatic stage to 0.80-fold of wild-type (WT) mice, 0.61 at early-symptomatic, and 0.49 at end stage of the disease. Local spinal glucose utilization (LSGU) was transiently increased to 1.19-fold in anterior GM at presymptomatic stage, which in turn progressively decreased to 0.84 and 0.60 at early-symptomatic and end stage of the disease. The LSGU/SBF ratio representing flow-metabolism uncoupling (FMU) preceded the sequential pathological changes in the spinal cord of ALS mice and was preferentially found in the affected region of ALS. The present study suggests that this early and progressive FMU could profoundly involve in the whole disease process as a vascular factor of ALS pathology, and could also be a potential target for therapeutic intervention of ALS.

Correlation between magnetic resonance T2 image signal intensity ratio and cell apoptosis in a rabbit spinal cord cervical myelopathy model.

PubMed

Ma, Lei; Zhang, Di; Chen, Wei; Shen, Yong; Zhang, Yingze; Ding, Wenyuan; Zhang, Wei; Wang, Linfeng; Yang, Dalong

2014-01-01

Cervical spondylotic myelopathy (CSM) is a common cause of disability in elderly patients. Previous studies have shown that spinal cord cell apoptosis due to spinal cord compression plays an important role in the pathology of myelopathy. Although changes in magnetic resonance imaging (MRI) T2 signal intensity ratio (SIR) are considered to be an indicator of CSM, little information is published supporting the correlation between changes in MRI signal and pathological changes. This study aims to testify the correlation between MRI T2 SIR changes and cell apoptosis using a CSM animal model. Forty-eight rabbits were randomly assigned to four groups: one control group and three experimental chronic compression groups, with each group containing 12 animals. Chronic compression of the cervical spinal cord was implemented in the experimental groups by implanting a screw in the C3 vertebra. The control group underwent sham surgery. Experimental groups were observed for 3, 6, or 9 months after surgery. MRI T2-weighted SIR Tarlov motor scores and cortical somatosensory-evoked potentials (CSEPs) were periodically monitored. At each time point, rabbits from one group were sacrificed to determine the level of apoptosis by histology (n = 6) and Western blotting (n = 6). Tarlov motor scores in the compression groups were lower at all time points than the control group scores, with the lowest score at 9 months (P < 0.001). Electrophysiological testing showed a significantly prolonged latency in CSEP in the compression groups compared with the control group. All rabbits in the compression groups showed higher MRI T2 SIR in the injury epicenter compared with controls, and higher SIR was also found at 9 months compared with 3 or 6 months. Histological analysis showed significant apoptosis in the spinal cord tissue in the compression groups, but not in the control group. There were significant differences in apoptosis degree over time (P < 0.001), with the 9-month group displaying the most severe spinal cord apoptosis. Spearman's rank correlation test showed that there was close relation between MRI SIR and degree of caspase-3 expression in Western blotting (r = 0.824. P < 0.001). Clear apoptosis of spinal cord tissue was observed during chronic focal spinal compression. Changes in MRI T2 SIR may be related to the severity of the apoptosis in cervical spinal cord.

Cannabidiol-treated rats exhibited higher motor score after cryogenic spinal cord injury.

PubMed

Kwiatkoski, Marcelo; Guimarães, Francisco Silveira; Del-Bel, Elaine

2012-04-01

Cannabidiol (CBD), a non-psychoactive constituent of cannabis, has been reported to induce neuroprotective effects in several experimental models of brain injury. We aimed at investigating whether this drug could also improve locomotor recovery of rats submitted to spinal cord cryoinjury. Rats were distributed into five experimental groups. Animals were submitted to laminectomy in vertebral segment T10 followed or not by application of liquid nitrogen for 5 s into the spinal cord at the same level to cause cryoinjury. The animals received injections of vehicle or CBD (20 mg/kg) immediately before, 3 h after and daily for 6 days after surgery. The Basso, Beattie, and Bresnahan motor evaluation test was used to assess motor function post-lesion one day before surgery and on the first, third, and seventh postoperative days. The extent of injury was evaluated by hematoxylin-eosin histology and FosB expression. Cryogenic lesion of the spinal cord resulted in a significant motor deficit. Cannabidiol-treated rats exhibited a higher Basso, Beattie, and Bresnahan locomotor score at the end of the first week after spinal cord injury: lesion + vehicle, day 1: zero, day 7: four, and lesion + Cannabidiol 20 mg/kg, day 1: zero, day 7: seven. Moreover, at this moment there was a significant reduction in the extent of tissue injury and FosB expression in the ventral horn of the spinal cord. The present study confirmed that application of liquid nitrogen to the spinal cord induces reproducible and quantifiable spinal cord injury associated with locomotor function impairments. Cannabidiol improved locomotor functional recovery and reduced injury extent, suggesting that it could be useful in the treatment of spinal cord lesions.

Dose-response study of spinal hyperbaric ropivacaine for cesarean section

PubMed Central

Chen, Xin-zhong; Chen, Hong; Lou, Ai-fei; Lü, Chang-cheng

2006-01-01

Background: Spinal hyperbaric ropivacaine may produce more predictable and reliable anesthesia than plain ropivacaine for cesarean section. The dose-response relation for spinal hyperbaric ropivacaine is undetermined. This double-blind, randomized, dose-response study determined the ED50 (50% effective dose) and ED95 (95% effective dose) of spinal hyperbaric ropivacaine for cesarean section anesthesia. Methods: Sixty parturients undergoing elective cesarean section delivery with use of combined spinal-epidural anesthesia were enrolled in this study. An epidural catheter was placed at the L1~L2 vertebral interspace, then lumbar puncture was performed at the L3~L4 vertebral interspace, and parturients were randomized to receive spinal hyperbaric ropivacaine in doses of 10.5 mg, 12 mg, 13.5 mg, or 15 mg in equal volumes of 3 ml. Sensory levels (pinprick) were assessed every 2.5 min until a T7 level was achieved and motor changes were assessed by modified Bromage Score. A dose was considered effective if an upper sensory level to pin prick of T7 or above was achieved and no intraoperative epidural supplement was required. ED50 and ED95 were determined with use of a logistic regression model. Results: ED50 (95% confidence interval) of spinal hyperbaric ropivacaine was determined to be 10.37 (5.23~11.59) mg and ED95 (95% confidence interval) to be 15.39 (13.81~23.59) mg. The maximum sensory block levels and the duration of motor block and the rate of hypotension, but not onset of anesthesia, were significantly related to the ropivacaine dose. Conclusion: The ED50 and ED95 of spinal hyperbaric ropivacaine for cesarean delivery under the conditions of this study were 10.37 mg and 15.39 mg, respectively. Ropivacaine is suitable for spinal anesthesia in cesarean delivery. PMID:17111469

Intraoperative electroacupuncture relieves remifentanil-induced postoperative hyperalgesia via inhibiting spinal glial activation in rats.

PubMed

Shi, Changxi; Liu, Yue; Zhang, Wei; Lei, Yishan; Lu, Cui'e; Sun, Rao; Sun, Yu'e; Jiang, Ming; Gu, Xiaoping; Ma, Zhengliang

2017-01-01

Background Accumulating studies have suggested that remifentanil, the widely-used opioid analgesic in clinical anesthesia, can activate the pronociceptive systems and enhance postoperative pain. Glial cells are thought to be implicated in remifentanil-induced hyperalgesia. Electroacupuncture is a complementary therapy to relieve various pain conditions with few side effects, and glial cells may be involved in its antinociceptive effect. In this study, we investigated whether intraoperative electroacupuncture could relieve remifentanil-induced postoperative hyperalgesia by inhibiting the activation of spinal glial cells, the production of spinal proinflammatory cytokines, and the activation of spinal mitogen-activated protein kinases. Methods A rat model of remifentanil-induced postoperative hyperalgesia was used in this study. Electroacupuncture during surgery was conducted at bilateral Zusanli (ST36) acupoints. Behavior tests, including mechanical allodynia and thermal hyperalgesia, were performed at different time points. Astrocytic marker glial fibrillary acidic protein, microglial marker Iba1, proinflammatory cytokines, and phosphorylated mitogen-activated protein kinases in the spinal cord were detected by Western blot and/or immunofluorescence. Results Mechanical allodynia and thermal hyperalgesia were induced by both surgical incision and remifentanil infusion, and remifentanil infusion significantly exaggerated and prolonged incision-induced pronociceptive effects. Glial fibrillary acidic protein, Iba1, proinflammatory cytokines (interleukin-1β and tumor necrosis factor-α), and phosphorylated mitogen-activated protein kinases (p-p38, p-JNK, and p-ERK1/2) were upregulated after surgical incision, remifentanil infusion, and especially after their combination. Intraoperative electroacupuncture significantly attenuated incision- and/or remifentanil-induced pronociceptive effects, spinal glial activation, proinflammatory cytokine upregulation, and phosphorylated mitogen-activated protein kinase upregulation. Conclusions Our study suggests that remifentanil-induced postoperative hyperalgesia can be relieved by intraoperative electroacupuncture via inhibiting the activation of spinal glial cells, the upregulation of spinal proinflammatory cytokines, and the activation of spinal mitogen-activated protein kinases.

Novel aspects of spinal cord evoked potentials (SCEPs) in the evaluation of dorso-ventral and lateral mechanical impacts on the spinal cord.

PubMed

Rad, Iman; Kouhzaei, Sogolie; Mobasheri, Hamid; Saberi, Hooshang

2015-02-01

The aim of the current study was to mimic mechanical impacts on the spinal cord by manifesting the effects of dorsoventral (DVMP) and lateral (LMP) mechanical pressure on neural activity to address points to be considered during surgery for different purposes, including spinal cord decompression. Spinal cords of anesthetized rats were compressed at T13. Different characteristics of axons, including vulnerability, excitability, and conduction velocity (CV), in response to promptness, severity, and duration of pressure were assessed by spinal cord evoked potentials (SCEPs). Real-time SCEPs recorded at L4-5 revealed N1, N2, and N3 peaks that were used to represent the activity of injured sensory afferents, interneurons, and MN fibers. The averaged SCEP recordings were fitted by trust-region algorithm to find the equivalent Gaussian and polynomial equations. The pyramidal and extrapyramidal pathways possessed CVs of 3-11 and 16-80 m s(-1), respectively. DVMP decreased the excitability of myelinated neural fibers in antidromic and orthodromic pathways. The excitability of fibers in extrapyramidal and pyramidal pathways of lateral corticospinal (LCS) and anterior corticospinal (ACS) tracts decreased following LMP. A significant drop in the amplitude of N3 and its conduction velocity (CV) revealed higher susceptibility of less-myelinated fibers to both DVMP and LMP. The best parametric fitting model for triplet healthy spinal cord CAP was a six-term Gaussian equation (G6) that fell into a five-term equation (G5) at the complete compression stage. The spinal cord is more susceptible to dorsoventral than lateral mechanical pressures, and this should be considered in spinal cord operations. SCEPs have shown promising capabilities for evaluating the severity of SCI and thus can be applied for diagnostic or prognostic intraoperative monitoring (IOM).

Mesenchymal Stem Cell-Based Therapy Improves Lower Limb Movement After Spinal Cord Ischemia in Rats.

PubMed

Takahashi, Shinya; Nakagawa, Kei; Tomiyasu, Mayumi; Nakashima, Ayumu; Katayama, Keijiro; Imura, Takeshi; Herlambang, Bagus; Okubo, Tomoe; Arihiro, Koji; Kawahara, Yumi; Yuge, Louis; Sueda, Taijiro

2018-05-01

Spinal cord ischemia is a devastating complication after thoracic and thoracoabdominal aortic operations. In this study, we aimed to investigate the effects of mesenchymal stem cells (MSCs), which have regenerative capability and exert paracrine actions on damaged tissues, injected into rat models of spinal cord ischemia-reperfusion injury. Forty-five Sprague-Dawley rats were divided into sham, phosphate-buffered saline (PBS), and MSC groups. Spinal cord ischemia was induced in the latter two groups by balloon occlusion of the thoracic aorta. MSCs and PBS were then immediately injected into the left carotid artery of the MSC and PBS groups, respectively. Hindlimb motor function was evaluated at 6 and 24 hours. The spinal cord was removed at 24 hours after ischemia-reperfusion injury, and histologic and immunohistochemical analyses and real-time polymerase chain reaction assessments were performed. Rats in the MSC and PBS groups showed flaccid paraparesis/paraplegia postoperatively. Hindlimb function was significantly better at 6 and 24 hours after ischemia-reperfusion injury in the MSC group than in the PBS group (p < 0.05). The number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive neuron cells in the spinal cord and the ratio of Bax to Bcl2 were significantly larger (p < 0.05) in the PBS group than in the MSC group. The injected MSCs were observed in the spinal cord 24 hours after ischemia-reperfusion injury. The MSC therapy by transarterial injection immediately after spinal cord ischemia-reperfusion injury may improve lower limb function by preventing apoptosis of neuron cells in the spinal cord. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Neural space and biomechanical integrity of the developing cervical spine in compression.

PubMed

Nuckley, David J; Van Nausdle, Joseph A; Eck, Michael P; Ching, Randal P

2007-03-15

A factorial study design was used to examine the biomechanical and neuroprotective integrity of the cervical spine throughout maturation using a postmortem baboon model. To investigate changes with spinal development that affect the neuroprotective ability of the cervical spine in compressive loading. Child spinal cord injuries claim and debilitate thousands of children in the United States each year. Many of these injuries are diagnostically and mechanistically difficult to classify, treat, and prevent. Biomechanical studies on maturing spinal tissues have identified decreased stiffness and tolerance characteristics for children compared with adults. Unfortunately, while neurologic deficit typically dictates functional outcome, no previous studies have examined the neuroprotective role of the pediatric cervical spine. Twenty-two postmortem baboon cervical spines across the developmental age spectrum were tested. Two functional spinal unit segments (Oc-C2, C3-C5, and C6-T1) were instrumented with transducers to measure dynamic changes in the spinal canal. These tissues were compressed to 70% strain dynamically, and the resultant mechanics and spinal canal occlusions were recorded. Classic injury patterns were observed in all of the specimens tested. The compressive mechanics exhibited a significant age relationship (P < 0.0001). Furthermore, while the peak-percent spinal canal occlusion was not age dependent, the percent occlusion just before failure did demonstrate a significant decrease with advancing age (P = 0.0001). The neuroprotective ability of the cervical spine preceding failure appears to be age dependent, where the young spine can produce greater spinal canal occlusions without failure than its adult counterpart. The overall percent of the spinal canal occluded during a compression injury was not age dependent; however, these data reveal the neuroprotective ability of the child spine to be more sensitive as an injury predictor than the biomechanical fracture data.

External cephalic version for breech presentation with or without spinal analgesia in nulliparous women at term: a randomized controlled trial.

PubMed

Weiniger, Carolyn F; Ginosar, Yehuda; Elchalal, Uriel; Sharon, Einav; Nokrian, Malka; Ezra, Yossef

2007-12-01

To compare the success of external cephalic version using spinal analgesia with no analgesia among nulliparas. A prospective randomized controlled trial was performed in a tertiary referral center delivery suite. Nulliparous women at term requesting external cephalic version for breech presentation were randomized to receive spinal analgesia (7.5 mg bupivacaine) or no analgesia before the external cephalic version. An experienced obstetrician performed the external cephalic version. Primary outcome was successful conversion to vertex presentation. Seventy-four women were enrolled, and 70 analyzed (36 spinal, 34 no analgesia). Successful external cephalic version occurred among 24 of 36 (66.7%) women randomized to receive spinal analgesia compared with 11 of 34 (32.4%) without, P=.004 (95% confidence interval [CI] of the difference: 0.0954-0.5513). External cephalic version with spinal analgesia resulted in a lower visual analog pain score, 1.76+/-2.74 compared with 6.84+/-3.08 without, P<.001. A secondary analysis logistic regression model demonstrated that the odds of external cephalic version success was 4.0-fold higher when performed with spinal analgesia P=.02 (95% CI, odds ratio [OR] 1.2-12.9). Complete breech presentation before attempting external cephalic version increased the odds of success 8.2-fold, P=.001 (95% CI, OR 2.2-30.3). Placental position, estimated fetal weight, and maternal weight did not contribute to the success rate when spinal analgesia was used. There were no cases of placental abruption or fetal distress. Administration of spinal analgesia significantly increases the success rate of external cephalic version among nulliparous women at term, which allows possible normal vaginal delivery. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00119184 I.

The Neuroprotective Effect of Kefir on Spinal Cord Ischemia/Reperfusion Injury in Rats

PubMed Central

Akman, Tarik; Yener, Ali Umit; Sehitoglu, Muserref Hilal; Yuksel, Yasemin; Cosar, Murat

2015-01-01

Objective The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of kefir on spinal cord ischemia injury in rats. Methods Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. Results The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (p<0.05). Catalase and superoxide dismutase levels of the kefir group were significantly higher than ischemia group (p<0.05). In histopathological samples, the kefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (p<0.05). In immunohistochemical staining, hipoxia-inducible factor-1α and caspase 3 immunopositive neurons were significantly decreased in kefir group compared with ischemia group (p<0.05). The neurological deficit scores of kefir group were significantly higher than ischemia group at 24 h (p<0.05). Conclusion Our study revealed that kefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future. PMID:26113960

Conditionally immortalized stem cell lines from human spinal cord retain regional identity and generate functional V2a interneurons and motorneurons.

PubMed

Cocks, Graham; Romanyuk, Nataliya; Amemori, Takashi; Jendelova, Pavla; Forostyak, Oksana; Jeffries, Aaron R; Perfect, Leo; Thuret, Sandrine; Dayanithi, Govindan; Sykova, Eva; Price, Jack

2013-06-07

The use of immortalized neural stem cells either as models of neural development in vitro or as cellular therapies in central nervous system (CNS) disorders has been controversial. This controversy has centered on the capacity of immortalized cells to retain characteristic features of the progenitor cells resident in the tissue of origin from which they were derived, and the potential for tumorogenicity as a result of immortalization. Here, we report the generation of conditionally immortalized neural stem cell lines from human fetal spinal cord tissue, which addresses these issues. Clonal neural stem cell lines were derived from 10-week-old human fetal spinal cord and conditionally immortalized with an inducible form of cMyc. The derived lines were karyotyped, transcriptionally profiled by microarray, and assessed against a panel of spinal cord progenitor markers with immunocytochemistry. In addition, the lines were differentiated and assessed for the presence of neuronal fate markers and functional calcium channels. Finally, a clonal line expressing eGFP was grafted into lesioned rat spinal cord and assessed for survival, differentiation characteristics, and tumorogenicity. We demonstrate that these clonal lines (a) retain a clear transcriptional signature of ventral spinal cord progenitors and a normal karyotype after extensive propagation in vitro, (b) differentiate into relevant ventral neuronal subtypes with functional T-, L-, N-, and P/Q-type Ca(2+) channels and spontaneous calcium oscillations, and (c) stably engraft into lesioned rat spinal cord without tumorogenicity. We propose that these cells represent a useful tool both for the in vitro study of differentiation into ventral spinal cord neuronal subtypes, and for examining the potential of conditionally immortalized neural stem cells to facilitate functional recovery after spinal cord injury or disease.

Episodic swimming in the larval zebrafish is generated by a spatially distributed spinal network with modular functional organization

PubMed Central

Wiggin, Timothy D.; Anderson, Tatiana M.; Eian, John; Peck, Jack H.

2012-01-01

Despite the diverse methods vertebrates use for locomotion, there is evidence that components of the locomotor central pattern generator (CPG) are conserved across species. When zebrafish begin swimming early in development, they perform short episodes of activity separated by periods of inactivity. Within these episodes, the trunk flexes with side-to-side alternation and the traveling body wave progresses rostrocaudally. To characterize the distribution of the swimming CPG along the rostrocaudal axis, we performed transections of the larval zebrafish spinal cord and induced fictive swimming using N-methyl-d-aspartate (NMDA). In both intact and spinalized larvae, bursting is found throughout the rostrocaudal extent of the spinal cord, and the properties of fictive swimming observed were dependent on the concentration of NMDA. We isolated series of contiguous spinal segments by performing multiple spinal transections on the same larvae. Although series from all regions of the spinal cord have the capacity to produce bursts, the capacity to produce organized episodes of fictive swimming has a rostral bias: in the rostral spinal cord, only 12 contiguous body segments are necessary, whereas 23 contiguous body segments are necessary in the caudal spinal cord. Shorter series of segments were often active but produced either continuous rhythmic bursting or sporadic, nonrhythmic bursting. Both episodic and continuous bursting alternated between the left and right sides of the body and showed rostrocaudal progression, demonstrating the functional dissociation of the circuits responsible for episodic structure and fine burst timing. These findings parallel results in mammalian locomotion, and we propose a hierarchical model of the larval zebrafish swimming CPG. PMID:22572943

Dynamic Detection of Spinal Cord Position During Postural Changes Using Near-Infrared Reflectometry.

PubMed

Wolf, Erich W

2015-08-01

Motion of the spinal cord relative to a spinal cord stimulator epidural electrode array can cause suboptimal stimulation: either noxious, inefficient, or insufficient. Adaptive stimulation attempts to mitigate these effects by modulating stimulation parameters in a position-dependent fashion. Near-infrared (NIR) reflectometry is demonstrated to provide real-time direct measurement of spinal cord position at the site of stimulation, which can facilitate closed-loop adaptive stimulation during static and dynamic motion states. A miniature sensor array consisting of an NIR light emitting diode flanked by phototransistors potted in epoxy was placed in the dorsal epidural space of a human cadaver at the T8 level via laminotomy. Turgor of the subarachnoid space was maintained by intrathecal infusion of saline. NIR reflectance was measured as the cadaver was rotated about its longitudinal axis on a gantry. NIR reflectance was correlated with gantry position and velocity. NIR reflectometry suggests gravitational force is the primary determinant of cord position in static, ordinal positions. Under dynamic motion conditions, there was statistically significant cross-correlation between reflectometry data and the tangential velocity squared, suggesting that centripetal force was the primary determinant of cord position as the gantry was rotated. Reflectometry data strongly correlated with a simple geometric model of anticipated spinal cord precession within the spinal canal. Spinal cord position during dynamic motion has been shown to differ from static predictions due to additional influences such as centripetal force. These findings underscore limitations in extrapolating spinal cord position from surrogates such as body position or body acceleration at sites remote from the stimulating electrodes. NIR reflectometry offers a real-time direct measure of spinal cord position in both static and dynamic motion states, which may facilitate closed-loop adaptive stimulation applications. © 2015 International Neuromodulation Society.

Bipedal locomotion of bonnet macaques after spinal cord injury.

PubMed

Babu, Rangasamy Suresh; Anand, P; Jeraud, Mathew; Periasamy, P; Namasivayam, A

2007-10-01

Experimental studies concerning the analysis of locomotor behavior in spinal cord injury research are widely performed in rodent models. The purpose of this study was to quantitatively evaluate the degree of functional recovery in reflex components and bipedal locomotor behavior of bonnet macaques (Macaca radiata) after spinal contusive injury. Six monkeys were tested for various reflex components (grasping, righting, hopping, extension withdrawal) and were trained preoperatively to walk in bipedal fashion on the simple and complex locomotor runways (narrow beam, grid, inclined plane, treadmill) of this investigation. The overall performance of the animals'motor behavior and the functional status of limb movements during bipedal locomotion were graded by the Combined Behavioral Score (CBS) system. Using the simple Allen weight-drop technique, a contusive injury was produced by dropping a 13-g weight from a height of 30 cm to the exposed spinal cord at the T12-L1 vertebral level of the trained monkeys. All the monkeys showed significant impairments in every reflex activity and in walking behavior during the early part of the postoperative period. In subsequent periods, the animals displayed mild alterations in certain reflex responses, such as grasping, extension withdrawal, and placing reflexes, which persisted through a 1-year follow-up. The contused animals traversed locomotor runways--narrow beam, incline plane, and grid runways--with more steps and few errors, as evaluated with the CBS system. Eventually, the behavioral performance of all spinal-contused monkeys recovered to near-preoperative level by the fifth postoperative month. The findings of this study reveal the recovery time course of various reflex components and bipedal locomotor behavior of spinal-contused macaques on runways for a postoperative period of up to 1 year. Our spinal cord research in primates is advantageous in understanding the characteristics of hind limb functions only, which possibly mimic the human motor behavior. This study may be also useful in detecting the beneficial effect of various donor tissue-neuroprotective drugs on the repair of impaired functions in a bipedal primate model of spinal injury.

A biomechanical study of artificial cervical discs using computer simulation.

PubMed

Ahn, Hyung Soo; DiAngelo, Denis J

2008-04-15

A virtual simulation model of the subaxial cervical spine was used to study the biomechanical effects of various disc prosthesis designs. To study the biomechanics of different design features of cervical disc arthroplasty devices. Disc arthroplasty is an alternative approach to cervical fusion surgery for restoring and maintaining motion at a diseased spinal segment. Different types of cervical disc arthroplasty devices exist and vary based on their placement and degrees of motion offered. A virtual dynamic model of the subaxial cervical spine was used to study 3 different prosthetic disc designs (PDD): (1) PDD-I: The center of rotation of a spherical joint located at the mid C5-C6 disc, (2) PDD-II: The center of rotation of a spherical joint located 6.5 mm below the mid C5-C6 disc, and (3) PDD-III: The center of rotation of a spherical joint in a plane located at the C5-C6 disc level. A constrained spherical joint placed at the disc level (PDD-I) significantly increased facet loads during extension. Lowering the rotational axis of the spherical joint towards the subjacent body (PDD-II) caused a marginal increase in facet loading during flexion, extension, and lateral bending. Lastly, unconstraining the spherical joint to move freely in a plane (PDD-III) minimized facet load build up during all loading modes. The simulation model showed the impact simple design changes may have on cervical disc dynamics. The predicted facet loads calculated from computer model have to be validated in the experimental study.

Three-dimensional finite element simulations of vertebral body thermal treatment (Invited Paper)

NASA Astrophysics Data System (ADS)

Ryan, Thomas P.; Patel, Samit J.; Morris, Ronit; Hoopes, P. J.; Bergeron, Jeffrey A.; Mahajan, Roop

2005-04-01

Lower back pain affects a large group of people worldwide and when in its early stages, has no viable interventional treatment. In order to avoid the eventuality of an invasive surgical procedure, which is further down the Care Pathway, an interventional treatment that is minimally invasive and arrests the patient's pain would be of tremendous clinical benefit. There is a hypothesis that if the basivertebral nerve in the vertebral body is defunctionalized, lower back pain may be lessened. To further investigate creating a means to provide localized thermal therapy, bench and animal studies were planned, but to help select the applicator configuration and placement, numerical modeling studies were undertaken. A 3D finite element model was utilized to predict the electric field pattern and power deposition pattern of radiofrequency (RF) based electrodes. Three types of tissues were modeled: 1) porcine (ex-vivo), ovine (in-vivo preclinical), and 3) human (ex-vivo, in-vivo). Two types of RF devices were simulated: 1) a pair of converging, hollow electrodes, and 2) an in-line pair of spaced-apart electrodes. Temperature distributions over time were plotted using the electric field results and the bioheat equation. Since the thermal and electrical properties of the vertebral bodies of porcine, ovine, and human tissue were not available, measurements were undertaken to capture these data to input into the model. The measurements of electrical and thermal properties of cancellous and cortical vertebral body were made over a range of temperatures. The simulation temperature results agreed with live animal and human cadaver studies. In addition, the lesion shapes predicted in the simulations matched CT and MRI studies done during the chronic ovine study, as well as histology results. In conclusion, the simulations aided in shaping and sizing the RF electrodes, as well as positioning them in the vertebral body structures to assure that the basivertebral nerve was ablated, but other neighboring structures such as the spinal cord and nerve roots were spared.

Differential effects of left and right neuropathy on opioid gene expression in lumbar spinal cord.

PubMed

Kononenko, Olga; Mityakina, Irina; Galatenko, Vladimir; Watanabe, Hiroyuki; Bazov, Igor; Gerashchenko, Anna; Sarkisyan, Daniil; Iatsyshyna, Anna; Yakovleva, Tatiana; Tonevitsky, Alex; Marklund, Niklas; Ossipov, Michael H; Bakalkin, Georgy

2018-05-28

The endogenous opioid system (EOS) controls the processing of nociceptive stimuli and is a pharmacological target for opioids. Alterations in expression of the EOS genes under neuropathic pain condition may account for low efficacy of opioid drugs. We here examined whether EOS expression patterns are altered in the lumbar spinal cord of the rats with spinal nerve ligation (SNL) as a neuropathic pain model. Effects of the left- and right-side SNL on expression of EOS genes in the ipsi- and contralateral spinal domains were analysed. The SNL-induced changes were complex and different between the genes; between the dorsal and ventral spinal domains; and between the left and right sides of the spinal cord. Prodynorphin (Pdyn) expression was upregulated in the ipsilateral dorsal domains by each the left and right-side SNL, while changes in expression of μ-opioid receptor (Oprm1) and proenkephalin (Penk) genes were dependent on the SNL side. Changes in expression of the Pdyn and κ-opioid receptor (Oprk1) genes were coordinated between the ipsi- and contralateral sides. Withdrawal response thresholds, indicators of mechanical allodynia correlated negatively with Pdyn expression in the right ventral domain after right side SNL. These findings suggest multiple roles of the EOS gene products in spinal sensitization and changes in motor reflexes, which may differ between the left and right sides. Copyright © 2018. Published by Elsevier B.V.

Transcutaneous electrical nerve stimulation attenuates postsurgical allodynia and suppresses spinal substance P and proinflammatory cytokine release in rats.

PubMed

Chen, Yu-Wen; Tzeng, Jann-Inn; Lin, Min-Fei; Hung, Ching-Hsia; Wang, Jhi-Joung

2015-01-01

Transcutaneous electrical nerve stimulation (TENS) is often used for management of chronic pain. The purpose of this study was to investigate whether TENS altered postincisional allodynia, substance P, and proinflammatory cytokines in a rat model of skin-muscle incision and retraction (SMIR). This was an experimental study. High-frequency (100-Hz) TENS therapy began on postoperative day 3 and was administered for 20 minutes daily to SMIR-operated rats by self-adhesive electrodes delivered to skin innervated via the ipsilateral dorsal rami of lumbar spinal nerves L1-L6 for the next 27 days. The expressions of substance P, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1β) in the spinal cord and mechanical sensitivity to von Frey stimuli (4g and 10g) were evaluated. The SMIR-operated rats displayed a marked hypersensitivity to von Frey stimuli on postoperative day 3. In contrast to the SMIR-operated rats, SMIR-operated rats after TENS administration showed a quick recovery of mechanical hypersensitivity. On postoperative days 3, 16, and 30, SMIR-operated rats exhibited an upregulation of substance P and cytokines (TNF-α, IL-6, and IL-1β) in the spinal cord, whereas SMIR-operated rats after TENS therapy inhibited that upregulation. By contrast, the placebo TENS following SMIR surgery did not alter mechanical hypersensitivity and the levels of spinal substance P, TNF-α, IL-6, and IL-1β. The experimental data are limited to animal models and cannot be generalized to postoperative pain in humans. The results revealed that TENS attenuates prolonged postoperative allodynia following SMIR surgery. Increased levels of spinal substance P and proinflammatory cytokines, activated after SMIR surgery, are important in the processing of persistent postsurgical allodynia. The protective effect of TENS may be related to the suppression of spinal substance P and proinflammatory cytokines in SMIR-operated rats. © 2015 American Physical Therapy Association.

Development and initial evaluation of the SCI-FI/AT

PubMed Central

Jette, Alan M.; Slavin, Mary D.; Ni, Pengsheng; Kisala, Pamela A.; Tulsky, David S.; Heinemann, Allen W.; Charlifue, Susie; Tate, Denise G.; Fyffe, Denise; Morse, Leslie; Marino, Ralph; Smith, Ian; Williams, Steve

2015-01-01

Objectives To describe the domain structure and calibration of the Spinal Cord Injury Functional Index for samples using Assistive Technology (SCI-FI/AT) and report the initial psychometric properties of each domain. Design Cross sectional survey followed by computerized adaptive test (CAT) simulations. Setting Inpatient and community settings. Participants A sample of 460 adults with traumatic spinal cord injury (SCI) stratified by level of injury, completeness of injury, and time since injury. Interventions None Main outcome measure SCI-FI/AT Results Confirmatory factor analysis (CFA) and Item response theory (IRT) analyses identified 4 unidimensional SCI-FI/AT domains: Basic Mobility (41 items) Self-care (71 items), Fine Motor Function (35 items), and Ambulation (29 items). High correlations of full item banks with 10-item simulated CATs indicated high accuracy of each CAT in estimating a person's function, and there was high measurement reliability for the simulated CAT scales compared with the full item bank. SCI-FI/AT item difficulties in the domains of Self-care, Fine Motor Function, and Ambulation were less difficult than the same items in the original SCI-FI item banks. Conclusion With the development of the SCI-FI/AT, clinicians and investigators have available multidimensional assessment scales that evaluate function for users of AT to complement the scales available in the original SCI-FI. PMID:26010975

Development and initial evaluation of the SCI-FI/AT.

PubMed

Jette, Alan M; Slavin, Mary D; Ni, Pengsheng; Kisala, Pamela A; Tulsky, David S; Heinemann, Allen W; Charlifue, Susie; Tate, Denise G; Fyffe, Denise; Morse, Leslie; Marino, Ralph; Smith, Ian; Williams, Steve

2015-05-01

To describe the domain structure and calibration of the Spinal Cord Injury Functional Index for samples using Assistive Technology (SCI-FI/AT) and report the initial psychometric properties of each domain. Cross sectional survey followed by computerized adaptive test (CAT) simulations. Inpatient and community settings. A sample of 460 adults with traumatic spinal cord injury (SCI) stratified by level of injury, completeness of injury, and time since injury. None SCI-FI/AT RESULTS: Confirmatory factor analysis (CFA) and Item response theory (IRT) analyses identified 4 unidimensional SCI-FI/AT domains: Basic Mobility (41 items) Self-care (71 items), Fine Motor Function (35 items), and Ambulation (29 items). High correlations of full item banks with 10-item simulated CATs indicated high accuracy of each CAT in estimating a person's function, and there was high measurement reliability for the simulated CAT scales compared with the full item bank. SCI-FI/AT item difficulties in the domains of Self-care, Fine Motor Function, and Ambulation were less difficult than the same items in the original SCI-FI item banks. With the development of the SCI-FI/AT, clinicians and investigators have available multidimensional assessment scales that evaluate function for users of AT to complement the scales available in the original SCI-FI.

New approach for graded compression spinal cord injuries in Rhesus macaque: method feasibility and preliminary observations.

PubMed

Guízar-Sahagún, Gabriel; Grijalva, Israel; Hernández-Godínez, Braulio; Franco-Bourland, Rebecca E; Cruz-Antonio, Leticia; Martínez-Cruz, Angelina; Ibáñez-Contreras, Alejandra; Madrazo, Ignacio

2011-12-01

Current models of spinal cord injury (SCI) have been ineffective for translational research. Primate blunt SCI, which more closely resembles human injury, could be a promising model to fill this gap. Graded compression SCI was produced by inflating at T9 an epidural balloon as a function of spinal canal dimensions in a non-uniform group of monkeys. Sham injury and cord compression by canal invasion of 50-75% produced minimal morpho-functional alterations, if at all. Canal invasion of 90-100% resulted in proportional functional deficits. Unexpectedly, these animals showed spontaneous gradual recovery over a 12-week period achieving quadruped walking, although with persistent absence of foot grasping reflex. Histopathology revealed predominance of central cord damage that correlated with functional status. Our preliminary results suggest that this model could potentially be a useful addition to translational work, but requires further validation by including animals with permanent injuries and expansion of replicates. © 2011 John Wiley & Sons A/S.

Does the baricity of bupivacaine influence intrathecal spread in the prolonged sitting position before elective cesarean delivery? A prospective randomized controlled study.

PubMed

Loubert, Christian; Hallworth, Stephen; Fernando, Roshan; Columb, Malachy; Patel, Nisa; Sarang, Kavita; Sodhi, Vinnie

2011-10-01

Difficulties in inserting an epidural catheter while performing combined spinal-epidural anesthesia for cesarean delivery may lead to undue delays between the spinal injection of the local anesthetic mixture and the adoption of the supine position with lateral tilt. We hypothesized that this delay may affect the intrathecal distribution of local anesthetic of different baricities such that hypobaric local anesthetic would lead to a higher sensory block level. Healthy parturients with uncomplicated pregnancies undergoing elective cesarean delivery under combined spinal-epidural anesthesia were enrolled in this prospective double-blind randomized controlled trial. The subjects were allocated to receive hyperbaric (hyperbaric group), isobaric (isobaric group), or hypobaric (hypobaric group) spinal bupivacaine 10 mg. After the spinal injection, the subjects remained in the sitting position for 5 minutes (to simulate difficulty in inserting the epidural catheter) before being helped into the supine lateral tilt position. The primary outcome was the sensory block level during the 25 minutes after the spinal injection. Other end points included motor block score, maternal hypotension, and vasopressor requirements. Data from 89 patients were analyzed. Patient characteristics were similar in all groups. The median [interquartile range] (95% confidence interval) sensory levels after spinal injection were significantly higher with decreasing baricity: hyperbaric T10 [T11-8] (T10-9), isobaric T9 [T10-7] (T9-7), and hypobaric T6 [T8-4] (T8-5) (P < 0.001, Cuzick trend). All patients in the hypobaric group reached a sensory block level of T4 at 25 minutes after spinal injection compared with 80% of the patients in both the isobaric and hyperbaric groups (P = 0.04; difference 20%, 95% confidence interval of difference 4%-33%). Significantly more patients in the hypobaric group had complete lower limb motor block (Bromage score = 4) (hyperbaric 43%, isobaric 63%, and hypobaric 90%; P < 0.001). The incidences of maternal hypotension and nausea and vomiting were similar among groups, although the ephedrine requirements were significantly increased in the isobaric and hypobaric groups by factors of 1.83 and 3.0, respectively, compared with the hyperbaric group (P < 0.001, Cuzick trend). We demonstrated that when parturients undergoing cesarean delivery were maintained in the sitting position for 5 minutes after spinal injection of the local anesthetic, hypobaric bupivacaine resulted in sensory block levels that were higher compared with isobaric and hyperbaric bupivacaine, respectively, during the study period.

Nonlinear optical techniques for imaging and manipulating the mouse central nervous system

NASA Astrophysics Data System (ADS)

Farrar, Matthew John

The spinal cord of vertebrates serves as the conduit for somatosensory information and motor control, as well as being the locus of neural circuits that govern fast reflexes and patterned behaviors, such as walking in mammals or swimming in fish. Consequently, pathologies of the spinal cord -such as spinal cord injury (SCI)- lead to loss of motor control and sensory perception, with accompanying decline in life expectancy and quality of life. Despite the devastating effects of these diseases, few therapies exist to substantially ameliorate patient outcome. In part, studies of spinal cord pathology have been limited by the inability to perform in vivo imaging at the level of cellular processes. The focus of this thesis is to present the underlying theory for and demonstration of novel multi-photon microscopy (MPM) and optical manipulation techniques as they apply to studies the mouse central nervous system (CNS), with an emphasis on the spinal cord. The scientific findings which have resulted from the implementation of these techniques are also presented. In particular, we have demonstrated that third harmonic generation is a dye-free method of imaging CNS myelin, a fundamental constituent of the spinal cord that is difficult to label using exogenous dyes and/or transgenic constructs. Since gaining optical access to the spinal cord is a prerequisite for spinal cord imaging, we review our development of a novel spinal cord imaging chamber and surgical procedure which allowed us to image for multiple weeks following implantation without the need for repeated surgeries. We also have used MPM to characterize spinal venous blood flow before and after point occlusions. We review a novel nonlinear microscopy technique that may serve to show optical interfaces in three dimensions inside scattering tissue. Finally, we discuss a model and show results of optoporation, a means of transfecting cells with genetic constructs. Brief reviews of MPM and SCI are also presented.

Subpial Adeno-associated Virus 9 (AAV9) Vector Delivery in Adult Mice.

PubMed

Tadokoro, Takahiro; Miyanohara, Atsushi; Navarro, Michael; Kamizato, Kota; Juhas, Stefan; Juhasova, Jana; Marsala, Silvia; Platoshyn, Oleksandr; Curtis, Erik; Gabel, Brandon; Ciacci, Joseph; Lukacova, Nada; Bimbova, Katarina; Marsala, Martin

2017-07-13

The successful development of a subpial adeno-associated virus 9 (AAV9) vector delivery technique in adult rats and pigs has been reported on previously. Using subpially-placed polyethylene catheters (PE-10 or PE-5) for AAV9 delivery, potent transgene expression through the spinal parenchyma (white and gray matter) in subpially-injected spinal segments has been demonstrated. Because of the wide range of transgenic mouse models of neurodegenerative diseases, there is a strong desire for the development of a potent central nervous system (CNS)-targeted vector delivery technique in adult mice. Accordingly, the present study describes the development of a spinal subpial vector delivery device and technique to permit safe and effective spinal AAV9 delivery in adult C57BL/6J mice. In spinally immobilized and anesthetized mice, the pia mater (cervical 1 and lumbar 1-2 spinal segmental level) was incised with a sharp 34 G needle using an XYZ manipulator. A second XYZ manipulator was then used to advance a blunt 36G needle into the lumbar and/or cervical subpial space. The AAV9 vector (3-5 µL; 1.2 x 10 13 genome copies (gc)) encoding green fluorescent protein (GFP) was then injected subpially. After injections, neurological function (motor and sensory) was assessed periodically, and animals were perfusion-fixed 14 days after AAV9 delivery with 4% paraformaldehyde. Analysis of horizontal or transverse spinal cord sections showed transgene expression throughout the entire spinal cord, in both gray and white matter. In addition, intense retrogradely-mediated GFP expression was seen in the descending motor axons and neurons in the motor cortex, nucleus ruber, and formatio reticularis. No neurological dysfunction was noted in any animals. These data show that the subpial vector delivery technique can successfully be used in adult mice, without causing procedure-related spinal cord injury, and is associated with highly potent transgene expression throughout the spinal neuraxis.

A pharmacokinetic-pharmacodynamic model for intrathecal baclofen in patients with severe spasticity.

PubMed

Heetla, H W; Proost, J H; Molmans, B H; Staal, M J; van Laar, T

2016-01-01

Intrathecal baclofen (ITB) has proven to be an effective and safe treatment for severe spasticity. However, although ITB is used extensively, clinical decisions are based on very scarce pharmacokinetic-pharmacodynamic (PKPD) data. The aim of this study was to measure baclofen CSF concentrations and clinical effects after administration of various ITB boluses in patients with spasticity and to create a PKPD model for ITB. Twelve patients with severe spasticity received four different bolus doses of ITB (0, 25, 50, 75 μg and an optional dose of 100 μg), administered via a catheter with the tip at thoracic level (Th) 10. After each bolus, 10 CSF samples were taken at fixed time intervals, using a catheter with the tip located at Th12. Clinical effect was assessed by measuring spasticity with the Modified Ashworth Scale (MAS). These data were used to develop a PKPD model. All patients achieved an adequate spasmolytic effect with ITB doses varying from 50 to 100 μg. No serious side effects were observed. CSF baclofen concentrations, as well as the clinical effects, correlated significantly with ITB doses. The PK model predicted a steep spinal concentration gradient of ITB along the spinal axis. The clinical effect could be predicted using a delayed-effect model. ITB is an effective and safe therapy with, however, a steep concentration gradient along the spinal axis. This means that the administered baclofen is staying mainly around the catheter tip, which stresses the importance to position the ITB catheter tip closely to the targeted spinal level. © 2015 The British Pharmacological Society.

Moving toward a standard for spinal fusion outcomes assessment.

PubMed

Blount, Kevin J; Krompinger, W Jay; Maljanian, Rose; Browner, Bruce D

2002-02-01

Previous spinal fusion outcomes assessment studies have been complicated by inconsistencies in evaluative criteria and consequent variations in results. As a result, a general consensus is lacking on how to achieve comprehensive outcomes assessment for spinal fusion surgeries. The purpose of this article is to report the most validated and frequently used assessment measures to facilitate comparable outcomes studies in the future. Twenty-seven spinal fusion outcomes studies published between 1990 and 2000 were retrospectively reviewed. Study characteristics such as design, evaluative measures, and assessment tools were recorded and analyzed. Based on the reviewed literature, an outcomes assessment model is proposed including the Short Form-36 Health Survey, the Oswestry Disability Questionnaire, the North American Spine Society Patient Satisfaction Index, the Prolo Economic Scale, a 0-10 analog pain scale, medication use, radiographically assessed fusion status, and a generalized complication rate.

Spinal cord, hypothalamic, and air temperature: interaction with arousal states in the marmot.

PubMed

Miller, V M; South, F E

1979-01-01

Yellow-bellied marmots, Marmota flaviventris, prepared with U-shaped thermodes in the epidural space of the thoracic vertebral canal, a thermode in the preoptic hypothalamus, and cortical surface and hippocampal electrodes, were used to investigate the interaction of arousal states with temperature regulation. It was found that arousal state of the animal influences the thermoregulatory responses initiated in either the spinal cord or hypothalamus. Further, changes in ambient temperature affected both the gain and the threshold of these responses. The interaction of the hypothalamus and spinal cord was not an additive function, however the threshold for shivering of each could be altered by temperature manipulation of the other. Future studies in modeling of temperature regulation should consider the contributions of temperature receptors of the spinal cord and the arousal state of the animal during the stimulation period.

Assessing Forelimb Function after Unilateral Cervical SCI using Novel Tasks: Limb Step-alternation, Postural Instability and Pasta Handling

PubMed Central

Schallert, Timothy; Schmidt, Christine E.

2013-01-01

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. A majority of the spinal cord injuries in humans occur at the cervical levels. Therefore, developing cervical injury models and developing relevant and sensitive behavioral tests is of great importance. Here we describe the use of a newly developed forelimb step-alternation test after cervical spinal cord injury in rats. In addition, we describe two behavioral tests that have not been used after spinal cord injury: a postural instability test (PIT), and a pasta-handling test. All three behavioral tests are highly sensitive to injury and are easy to use. Therefore, we feel that these behavioral tests can be instrumental in investigating therapeutic strategies after cSCI. PMID:24084700

Assessing forelimb function after unilateral cervical SCI using novel tasks: limb step-alternation, postural instability and pasta handling.

PubMed

Khaing, Zin Z; Geissler, Sydney A; Schallert, Timothy; Schmidt, Christine E

2013-09-16

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. A majority of the spinal cord injuries in humans occur at the cervical levels. Therefore, developing cervical injury models and developing relevant and sensitive behavioral tests is of great importance. Here we describe the use of a newly developed forelimb step-alternation test after cervical spinal cord injury in rats. In addition, we describe two behavioral tests that have not been used after spinal cord injury: a postural instability test (PIT), and a pasta-handling test. All three behavioral tests are highly sensitive to injury and are easy to use. Therefore, we feel that these behavioral tests can be instrumental in investigating therapeutic strategies after cSCI.

Analysis of the fibroblast growth factor system reveals alterations in a mouse model of spinal muscular atrophy.

PubMed

Hensel, Niko; Ratzka, Andreas; Brinkmann, Hella; Klimaschewski, Lars; Grothe, Claudia; Claus, Peter

2012-01-01

The monogenetic disease Spinal Muscular Atrophy (SMA) is characterized by a progressive loss of motoneurons leading to muscle weakness and atrophy due to severe reduction of the Survival of Motoneuron (SMN) protein. Several models of SMA show deficits in neurite outgrowth and maintenance of neuromuscular junction (NMJ) structure. Survival of motoneurons, axonal outgrowth and formation of NMJ is controlled by neurotrophic factors such as the Fibroblast Growth Factor (FGF) system. Besides their classical role as extracellular ligands, some FGFs exert also intracellular functions controlling neuronal differentiation. We have previously shown that intracellular FGF-2 binds to SMN and regulates the number of a subtype of nuclear bodies which are reduced in SMA patients. In the light of these findings, we systematically analyzed the FGF-system comprising five canonical receptors and 22 ligands in a severe mouse model of SMA. In this study, we demonstrate widespread alterations of the FGF-system in both muscle and spinal cord. Importantly, FGF-receptor 1 is upregulated in spinal cord at a pre-symptomatic stage as well as in a mouse motoneuron-like cell-line NSC34 based model of SMA. Consistent with that, phosphorylations of FGFR-downstream targets Akt and ERK are increased. Moreover, ERK hyper-phosphorylation is functionally linked to FGFR-1 as revealed by receptor inhibition experiments. Our study shows that the FGF system is dysregulated at an early stage in SMA and may contribute to the SMA pathogenesis.

Combination of edaravone and neural stem cell transplantation repairs injured spinal cord in rats.

PubMed

Song, Y Y; Peng, C G; Ye, X B

2015-12-29

This study sought to observe the effect of the combination of edaravone and neural stem cell (NSC) transplantation on the repair of complete spinal cord transection in rats. Eighty adult female Sprague-Dawley (SD) rats were used to establish the injury model of complete spinal cord transection at T9. Animals were divided randomly into four groups (N = 20 each): control, edaravone, transplantation, and edaravone + transplantation. The recovery of spinal function was evaluated with the Basso, Beattie, Bresnahan (BBB) rating scale on days 1, 3, and 7 each week after the surgery. After 8 weeks, the BBB scores of the control, edaravone, transplantation, and combination groups were 4.21 ± 0.11, 8.46 ± 0.1, 8.54 ± 0.13, and 11.21 ± 0.14, respectively. At 8 weeks after surgery, the spinal cord was collected; the survival and transportation of transplanted cells were observed with PKH-26 labeling, and the regeneration and distribution of spinal nerve fibers with fluorescent-gold (FG) retrograde tracing. Five rats died due to the injury. PKH-26-labeled NSCs had migrated into the spinal cord. A few intact nerve fibers and pyramidal neurons passed the injured area in the transplantation and combination groups. The numbers of PKH-26-labeled cells and FG-labeled nerve fibers were in the order: combination group > edaravone group and transplantation group > control group (P < 0.05 for each). Thus, edaravone can enhance the survival and differentiation of NSCs in injured areas; edaravone with NSC transplantation can improve the effectiveness of spinal cord injury repair in rats.

Reduction of microhemorrhages in the spinal cord of symptomatic ALS mice after intravenous human bone marrow stem cell transplantation accompanies repair of the blood-spinal cord barrier.

PubMed

Eve, David J; Steiner, George; Mahendrasah, Ajay; Sanberg, Paul R; Kurien, Crupa; Thomson, Avery; Borlongan, Cesar V; Garbuzova-Davis, Svitlana

2018-02-13

Blood-spinal cord barrier (BSCB) alterations, including capillary rupture, have been demonstrated in animal models of amyotrophic lateral sclerosis (ALS) and ALS patients. To date, treatment to restore BSCB in ALS is underexplored. Here, we evaluated whether intravenous transplantation of human bone marrow CD34 + (hBM34 + ) cells into symptomatic ALS mice leads to restoration of capillary integrity in the spinal cord as determined by detection of microhemorrhages. Three different doses of hBM34 + cells (5 × 10 4 , 5 × 10 5 or 1 × 10 6 ) or media were intravenously injected into symptomatic G93A SOD1 mice at 13 weeks of age. Microhemorrhages were determined in the cervical and lumbar spinal cords of mice at 4 weeks post-treatment, as revealed by Perls' Prussian blue staining for ferric iron. Numerous microhemorrhages were observed in the gray and white matter of the spinal cords in media-treated mice, with a greater number of capillary ruptures within the ventral horn of both segments. In cell-treated mice, microhemorrhage numbers in the cervical and lumbar spinal cords were inversely related to administered cell doses. In particular, the pervasive microvascular ruptures determined in the spinal cords in late symptomatic ALS mice were significantly decreased by the highest cell dose, suggestive of BSCB repair by grafted hBM34 + cells. The study results provide translational outcomes supporting transplantation of hBM34 + cells at an optimal dose as a potential therapeutic strategy for BSCB repair in ALS patients.

Intraspinal AAV Injections Immediately Rostral to a Thoracic Spinal Cord Injury Site Efficiently Transduces Neurons in Spinal Cord and Brain

PubMed Central

Klaw, Michelle C; Xu, Chen; Tom, Veronica J

2013-01-01

In the vast majority of studies utilizing adeno-associated virus (AAV) in central nervous system applications, including those published with spinal cord injury (SCI) models, AAV has been administered at the level of the cell body of neurons targeted for genetic modification, resulting in transduction of neurons in the vicinity of the injection site. However, as SCI interrupts many axon tracts, it may be more beneficial to transduce a diverse pool of supraspinal neurons. We determined if descending axons severed by SCI are capable of retrogradely transporting AAV to remotely transduce a variety of brain regions. Different AAV serotypes encoding the reporter green fluorescent protein (GFP) were injected into gray and white matter immediately rostral to a spinal transection site. This resulted in the transduction of thousands of neurons within the spinal cord and in multiple regions within the brainstem that project to spinal cord. In addition, we established that different serotypes had disparate regional specificity and that AAV5 transduced the most brain and spinal cord neurons. This is the first demonstration that retrograde transport of AAV by axons severed by SCI is an effective means to transduce a collection of supraspinal neurons. Thus, we identify a novel, minimally invasive means to transduce a variety of neuronal populations within both the spinal cord and the brain following SCI. This paradigm to broadly distribute viral vectors has the potential to be an important component of a combinatorial strategy to promote functional axonal regeneration. PMID:23881451

Electrical peripheral nerve stimulation relieves bone cancer pain by inducing Arc protein expression in the spinal cord dorsal horn

PubMed Central

Sun, Ke-fu; Feng, Wan-wen; Liu, Yue-peng; Dong, Yan-bin; Gao, Li; Yang, Hui-lin

2018-01-01

Objective The analgesic effect on chronic pain of peripheral nerve stimulation (PNS) has been proven, but its underlying mechanism remains unknown. Therefore, this study aimed to assess the analgesic effect of PNS on bone cancer pain in a rat model and to explore the underlying mechanism. Materials and methods PNS on sciatic nerves with bipolar electrode was performed in both naïve and bone cancer pain model rats. Then, the protein levels of activity-regulated cytoskeleton-associated protein (Arc), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid–type glutamate receptor 1 (GluA1), and phosphate N-methyl-d-aspartic acid-type glutamate receptor subunit 2B (pGluNR2B) in spinal cord were evaluated by immunohistochemistry and Western blotting. Thermal paw withdraw latency and mechanical paw withdraw threshold were used to estimate the analgesic effect of PNS on bone cancer pain. Intrathecal administration of Arc shRNA was used to inhibit Arc expression in the spinal cord. Results PNS at 60 and 120 Hz for 20 min overtly induced Arc expression in the spinal cord, increased thermal pain thresholds in naïve rats, and relieved bone cancer pain; meanwhile, 10 Hz PNS did not achieve those results. In addition, PNS at 60 and 120 Hz also reduced the expression of GluA1, but not pGluNR2B, in the spinal cord. Finally, the anti-nociceptive effect and GluA1 downregulation induced by PNS were inhibited by intrathecal administration of Arc shRNA. Conclusion PNS (60 Hz, 0.3 mA) can relieve bone-cancer-induced allodynia and hyperalgesia by upregulating Arc protein expression and then by decreasing GluA1 transcription in the spinal cord dorsal horn. PMID:29606887

MANF attenuates neuronal apoptosis and promotes behavioral recovery via Akt/MDM-2/p53 pathway after traumatic spinal cord injury in rats.

PubMed

Gao, Liansheng; Xu, Weilin; Fan, Shuangbo; Li, Tao; Zhao, Tengfei; Ying, Guangyu; Zheng, Jingwei; Li, Jianru; Zhang, Zhongyuan; Yan, Feng; Zhu, Yongjian; Chen, Gao

2018-05-24

The aim of this study was to investigate the potential effect and mechanism of action of MANF in attenuating neuronal apoptosis following t-SCI. A clip compressive model was used to induce a crush injury of the spinal cord in a total of 230 rats. The Basso, Beattie, and Bresnahan (BBB) score, spinal cord water content, and blood spinal cord barrier (BSCB) permeability were evaluated. The expression levels of MANF and its downstream proteins were examined by western blotting. Immunofluorescence staining of MANF, NeuN, GFAP, Iba-1, cleaved caspase-3, and TUNEL staining were also performed. Cells were counted in six randomly selected fields in the gray matter regions of the sections from two spinal cord sites (2 mm rostral and caudal to the epicenter of the injury) per sample. A cell-based mechanical injury model was also conducted using SH-SY5Y cells. Cell apoptosis and viability were assessed by flow cytometry, an MTT assay, and trypan blue staining. Subcellular structures were observed by transmission electron microscopy. MANF was mainly expressed in neurons. The expression levels of MANF, and its downstream target, p-Akt, were gradually increased and after t-SCI. Treatment with MANF increased Bcl-2 and decreased Bax and CC-3 levels; these effects were reversed on treatment with MK2206. The BBB score, spinal cord water content, and BSCB destruction were also ameliorated by MANF treatment. MANF decreases neuronal apoptosis and improves neurological function through Akt/MDM-2/p53 pathway after t-SCI. Therefore, MANF might be a potential treatment for patients with t-SCI.© 2018 BioFactors, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

The Protective Effect of Curcumin on a Spinal Cord Ischemia-Reperfusion Injury Model.

PubMed

Akar, İlker; İnce, İlker; Arici, Akgül; Benli, İsmail; Aslan, Cemal; Şenol, Sefa; Demir, Osman; Altunkas, Fatih; Altındeger, Nuray; Akbas, Ali

2017-07-01

The purpose of this study is to investigate the neurological, biochemical, and histopathologic effects of both the acute and maintenance treatment of curcumin on an experimental spinal cord ischemia-reperfusion injury model in rats. The animals were randomly divided into 4 groups: (1) Sham, (2) ischemia-reperfusion (IR), (3) curcumin, and (4) solvent. Spinal cord ischemia was induced by clamping the aorta with minivascular clamps at a position just below the left renal artery and just proximal to the aortic bifurcation for 45 min. After 72 hr of reperfusion, neurological function was evaluated with a modified Tarlov score. In spinal cords, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and nitric oxide (NO) levels were detected biochemically. Immunohistochemical staining was performed by antibodies against interleukin-6 (IL-6) and myeloperoxidase. Histopathologic changes were examined with hematoxylin and eosin staining. Although MDA tissue levels were elevated significantly in the IR group compared with the sham group, SOD and GPx levels decreased. After the administration of curcumin, MDA levels in the spinal cord decreased, and SOD and GPx levels increased. Those changes were statistically significant. There was no significance at NO levels. Among all groups, there was no difference in IL-6 and myeloperoxidase immunostaining. Histopathological analysis showed that histopathological changes in the IR group were improved by curcumin treatment. In the curcumin group, neurological outcome scores were significantly better statistically when compared with the IR group. We believe that curcumin possesses antioxidant, antiproliferative, and anticarcinogenic properties and may be an effective drug for the prevention of spinal cord IR injury in light of the neurologic, biochemical, and histopathological data of this study and published scientific literature. Copyright © 2017 Elsevier Inc. All rights reserved.

[Effect of electroacupuncture on phosphorylation of NR2B at Tyr 1742 site in the spinal dorsal horn of CFA rats].

PubMed

Liang, Yi; Fang, Jian-Qiao; Fang, Jun-Fan; Du, Jun-Ying; Qiu, Yu-Jie; Liu, Jin

2013-10-01

To observe the effect of electroacupuncture (EA) on phosphorylation of spinal NR2B at Tyr 1742 site in complete Freund's adjuvant (CFA) induced inflammatory pain rats. METHods Forty male Sprague Dawley rats were randomly divided into normal group (N group, n = 10), the model group (CFA group, n = 15), and the EA group (n = 15). The inflammatory pain model was established by subcutaneous injecting CFA (0.1 mL per rat) into the right hind paw. Paw withdrawal thresholds (PWTs) were measured before CFA injection (as the base), as well as at 24 h, 25 h, 3rd day, and 7th day after CFA injection. Phosphorylation of NR2B at Tyr 1742 site in the ispilateral spinal dorsal horn at the 3rd day post-injection were detected using immunohistochemical assay. PWTs in the CFA group were significantly lower than those of the N group at every detective time point post-injection (P < 0.01). PWTs were obviously lower in the EA group than in the N group at 24 h post-injection (P < 0.01). It showed increasing tendency, markedly higher than those of the CFA group at 25 h and 3rd day post-injection (P < 0.01). Compared with the N group, the ratio of p-NR2B positive cells in the ispilateral spinal dorsal horn of rats in the CFA group was up-regulated. Compared with the CFA group, the ratio of p-NR2B positive cells in the ispilateral spinal dorsal horn of rats showed a decreasing tendency in the EA group. EA might effectively inhibit CFA-induced inflammatory pain possibly associated with down-regulating phosphorylation of NR2B at Tyr 1742 site in the ispilateral spinal dorsal horn.

Can Recognition of Spinal Ischemia Be Improved? Application of Motor-Evoked Potentials, Serum Markers, and Breath Gas Analysis in an Acutely Instrumented Pig Model.

PubMed

Püschel, Anja; Ebel, Rasmus; Fuchs, Patricia; Hofmann, Janet; Schubert, Jochen K; Roesner, Jan P; Bergt, Stefan; Wree, Andreas; Vollmar, Brigitte; Klar, Ernst; Bünger, Carsten M; Kischkel, Sabine

2018-05-01

Paraplegia due to spinal cord ischemia (SCI) is a serious complication after repair of thoracoabdominal aortic aneurysms. For prevention and early treatment of spinal ischemia, intraoperative monitoring of spinal cord integrity is essential. This study was intended to improve recognition of SCI through a combination of transcranial motor-evoked potentials (tc-MEPs), serum markers, and innovative breath analysis. In 9 female German Landrace pigs, tc-MEPs were captured, markers of neuronal damage were determined in blood, and volatile organic compounds (VOCs) were analyzed in exhaled air. After thoraco-phrenico-laparotomy, SCI was initiated through sequential clamping (n = 4) or permanently ligating (n = 5) SAs of the abdominal and thoracic aorta in caudocranial orientation until a drop in the tc-MEPs to at least 25% of the baseline was recorded. VOCs in breath were determined by means of solid-phase microextraction coupled with gas chromatography-mass spectrometry. After waking up, clinical and neurological status was evaluated (Tarlov score). Spinal cord histology was obtained in postmortem. Permanent vessel ligature induced a worse neurological outcome and a higher number of necrotic motor neurons compared to clamping. Changes of serum markers remained unspecific. After laparotomy, exhaled acetone and isopropanol showed highest concentrations, and pentane and hexane increased during ischemia-reperfusion injury. To mimic spinal ischemia occurring in humans during aortic aneurysm repair, animal models have to be meticulously evaluated concerning vascular anatomy and function. Volatiles from breath indicated metabolic stress during surgery and oxidative damage through ischemia reperfusion. Breath VOCs may provide complimentary information to conventional monitoring methods. Copyright © 2018 Elsevier Inc. All rights reserved.

Delayed Disease Onset and Extended Survival in the SOD1G93A Rat Model of Amyotrophic Lateral Sclerosis after Suppression of Mutant SOD1 in the Motor Cortex

PubMed Central

Thomsen, Gretchen M.; Gowing, Genevieve; Latter, Jessica; Chen, Maximus; Vit, Jean-Philippe; Staggenborg, Kevin; Avalos, Pablo; Alkaslasi, Mor; Ferraiuolo, Laura; Likhite, Shibi; Kaspar, Brian K.

2014-01-01

Sporadic amyotrophic lateral sclerosis (ALS) is a fatal disease with unknown etiology, characterized by a progressive loss of motor neurons leading to paralysis and death typically within 3–5 years of onset. Recently, there has been remarkable progress in understanding inherited forms of ALS in which well defined mutations are known to cause the disease. Rodent models in which the superoxide dismutase-1 (SOD1) mutation is overexpressed recapitulate hallmark signs of ALS in patients. Early anatomical changes in mouse models of fALS are seen in the neuromuscular junctions (NMJs) and lower motor neurons, and selective reduction of toxic mutant SOD1 in the spinal cord and muscle of these models has beneficial effects. Therefore, much of ALS research has focused on spinal motor neuron and NMJ aspects of the disease. Here we show that, in the SOD1G93A rat model of ALS, spinal motor neuron loss occurs presymptomatically and before degeneration of ventral root axons and denervation of NMJs. Although overt cell death of corticospinal motor neurons does not occur until disease endpoint, we wanted to establish whether the upper motor neuron might still play a critical role in disease progression. Surprisingly, the knockdown of mutant SOD1 in only the motor cortex of presymptomatic SOD1G93A rats through targeted delivery of AAV9–SOD1–shRNA resulted in a significant delay of disease onset, expansion of lifespan, enhanced survival of spinal motor neurons, and maintenance of NMJs. This datum suggests an early dysfunction and thus an important role of the upper motor neuron in this animal model of ALS and perhaps patients with the disease. PMID:25411487

Effects of core body temperature on changes in spinal somatosensory-evoked potential in acute spinal cord compression injury: an experimental study in the rat.

PubMed

Jou, I M

2000-08-01

Acute spinal cord injury was induced by a clip compression model in rats to approximate spinal cord injury encountered in spinal surgery. Spinal somatosensory-evoked potential neuromonitoring was used to study the electrophysiologic change. To compare and correlate changes in evoked potential after acute compression at different core temperatures with postoperative neurologic function and histologic change, to evaluate current intraoperative neuromonitoring warning criteria for neural damage, and to confirm the protective effect of hypothermia in acute spinal cord compression injury by electrophysiologic, histologic, and clinical observation. With the increase in aggressive correction of spinal deformities, and the invasiveness of surgical instruments, the incidence of neurologic complication appears to have increased despite the availability of sensitive intraoperative neuromonitoring techniques designed to alert surgeons to impending neural damage. Many reasons have been given for the frequent failures of neuromonitoring, but the influence of temperature-a very important and frequently encountered factor-on evoked potential has not been well documented. Specifically, decrease in amplitude and elongation of latency seem not to have been sufficiently taken into account when intraoperative neuromonitoring levels were interpreted and when acceptable intraoperative warning criteria were determined. Experimental acute spinal cord injury was induced in rats by clip compression for two different intervals and at three different core temperatures. Spinal somatosensory-evoked potential, elicited by stimulating the median nerve and recorded from the cervical interspinous C2-C3, was monitored immediately before and after compression, and at 15-minute intervals for 1 hour. Spinal somatosensory-evoked potential change is almost parallel to temperature-based amplitude reduction and latency elongation. Significant neurologic damage induced by acute compression of the cervical spinal cord produced a degree of effect on the amplitude of spinal somatosensory-evoked potential in normothermic conditions that differed from the effect in moderately hypothermic conditions. Using the same electromonitoring criteria,moderately hypothermic groups showed a significantly higher false-negative rate statistically (35%) than normothermic groups (10%). Systemic cooling may protect against the detrimental effects of aggressive spinal surgical procedures. There is still not enough published information available to establish statistically and ethically acceptable intraoperative neuromonitoring warning and intervention criteria conclusively. Therefore, an urgent need exists for further investigation. Although a reduction of more than 50% in evoked potential still seems acceptable as an indicator of impending neural function loss, maintenance of more than 50% of baseline evoked potential is no guarantee of normal postoperative neural function, especially at lower than normal temperatures.

The effect of whole-body resonance vibration in a porcine model of spinal cord injury.

PubMed

Streijger, Femke; Lee, Jae H T; Chak, Jason; Dressler, Dan; Manouchehri, Neda; Okon, Elena B; Anderson, Lisa M; Melnyk, Angela D; Cripton, Peter A; Kwon, Brian K

2015-06-15

Whole-body vibration has been identified as a potential stressor to spinal cord injury (SCI) patients during pre-hospital transportation. However, the effect that such vibration has on the acutely injured spinal cord is largely unknown, particularly in the frequency domain of 5 Hz in which resonance of the spine occurs. The objective of the study was to investigate the consequences of resonance vibration on the injured spinal cord. Using our previously characterized porcine model of SCI, we subjected animals to resonance vibration (5.7±0.46 Hz) or no vibration for a period of 1.5 or 3.0 h. Locomotor function was assessed weekly and cerebrospinal fluid (CSF) samples were collected to assess different inflammatory and injury severity markers. Spinal cords were evaluated histologically to quantify preserved white and gray matter. No significant differences were found between groups for CSF levels of monocyte chemotactic protein-1, interleukin 6 (IL-6) and lL-8. Glial fibrillary acidic protein levels were lower in the resonance vibration group, compared with the non-vibrated control group. Spared white matter tissue was increased within the vibrated group at 7 d post-injury but this difference was not apparent at the 12-week time-point. No significant difference was observed in locomotor recovery following resonance vibration of the spine. Here, we demonstrate that exposure to resonance vibration for 1.5 or 3 h following SCI in our porcine model is not detrimental to the functional or histological outcomes. Our observation that a 3.0-h period of vibration at resonance frequency induces modest histological improvement at one week post-injury warrants further study.

Human Glial-Restricted Progenitor Transplantation into Cervical Spinal Cord of the SOD1G93A Mouse Model of ALS

PubMed Central

Lepore, Angelo C.; O'Donnell, John; Kim, Andrew S.; Williams, Timothy; Tuteja, Alicia; Rao, Mahendra S.; Kelley, Linda L.; Campanelli, James T.; Maragakis, Nicholas J.

2011-01-01

Cellular abnormalities are not limited to motor neurons in amyotrophic lateral sclerosis (ALS). There are numerous observations of astrocyte dysfunction in both humans with ALS and in SOD1G93A rodents, a widely studied ALS model. The present study therapeutically targeted astrocyte replacement in this model via transplantation of human Glial-Restricted Progenitors (hGRPs), lineage-restricted progenitors derived from human fetal neural tissue. Our previous findings demonstrated that transplantation of rodent-derived GRPs into cervical spinal cord ventral gray matter (in order to target therapy to diaphragmatic function) resulted in therapeutic efficacy in the SOD1G93A rat. Those findings demonstrated the feasibility and efficacy of transplantation-based astrocyte replacement for ALS, and also show that targeted multi-segmental cell delivery to cervical spinal cord is a promising therapeutic strategy, particularly because of its relevance to addressing respiratory compromise associated with ALS. The present study investigated the safety and in vivo survival, distribution, differentiation, and potential efficacy of hGRPs in the SOD1G93A mouse. hGRP transplants robustly survived and migrated in both gray and white matter and differentiated into astrocytes in SOD1G93A mice spinal cord, despite ongoing disease progression. However, cervical spinal cord transplants did not result in motor neuron protection or any therapeutic benefits on functional outcome measures. This study provides an in vivo characterization of this glial progenitor cell and provides a foundation for understanding their capacity for survival, integration within host tissues, differentiation into glial subtypes, migration, and lack of toxicity or tumor formation. PMID:21998733

Activation of spinal and supraspinal cannabinoid-1 receptors lead to antinociception in a rat model of neuropathic spinal cord injury pain

PubMed Central

Hama, Aldric; Sagen, Jacqueline

2011-01-01

Activation of CNS cannabinoid subtype-1 (CB1) receptors has been shown to mediate the antinociceptive and other effects of systemically administered CB receptor agonists. The endogenous peptide CB receptor ligand hemopressin (HE) has previously demonstrated an antinociceptive effect in rats with a hind paw inflammation, without exhibiting characteristic CB1 receptor-mediated side-effects. The current study evaluated the effect of intrathecal (i.t.) and intracerebroventricular (i.c.v.) injection of HE in a rat model of neuropathic spinal cord injury (SCI) pain. The non-subtype selective CB receptor agonist WIN 55,212-2 was also centrally administered in SCI rats as a comparator. Four weeks following an acute compression of the mid-thoracic spinal cord, rats displayed markedly decreased hind paw withdrawal thresholds, indicative of below-level neuropathic pain. Central administration of WIN 55,212-2 significantly increased withdrawal thresholds, whereas HE did not. Hemopressin has been reported to block CB1 receptors in vitro, similar to the CB1 receptor antagonist rimonabant. Pretreatment with rimonabant completely blocked the antinociceptive effect of centrally administered WIN 55,212-2, but pretreatment with HE did not. While the data confirm that activation of either supraspinal or spinal CB1 receptors leads to significant antinociception in SCI rats, the current data do not support an antinociceptive effect from an acute blockade of central CB1 receptors, HE’s putative antinociceptive mechanism, in neuropathic SCI rats. Although such a mechanism could be useful in other models of pain with a significant inflammatory component, the current data indicate that activation of CB1 receptors is needed to ameliorate neuropathic SCI pain. PMID:21813113

Optimization of Spinal Muscular Atrophy subject's muscle activity during gait

NASA Astrophysics Data System (ADS)

Umat, Gazlia; Rambely, Azmin Sham

2014-06-01

Spinal Muscular Atrophy (SMA) is a hereditary disease related muscle nerve disorder caused by degeneration of the anterior cells of the spinal cord. SMA is divided into four types according to the degree of seriousness. SMA patients show different gait with normal people. Therefore, this study focused on the effects of SMA patient muscle actions and the difference that exists between SMA subjects and normal subjects. Therefore, the electromyography (EMG) test will be used to track the behavior of muscle during walking and optimization methods are used to get the muscle stress that is capable of doing the work while walking. Involved objective function is non-linear function of the quadratic and cubic functions. The study concludes with a comparison of the objective function using the force that sought to use the moment of previous studies and the objective function using the data obtained from EMG. The results shows that the same muscles, peroneus longus and bisepsfemoris, were used during walking activity by SMA subjects and control subjects. Muscle stress force best solution achieved from part D in simulation carried out.

Effective scattering coefficient of the cerebral spinal fluid in adult head models for diffuse optical imaging

NASA Astrophysics Data System (ADS)

Custo, Anna; Wells, William M., III; Barnett, Alex H.; Hillman, Elizabeth M. C.; Boas, David A.

2006-07-01

An efficient computation of the time-dependent forward solution for photon transport in a head model is a key capability for performing accurate inversion for functional diffuse optical imaging of the brain. The diffusion approximation to photon transport is much faster to simulate than the physically correct radiative transport equation (RTE); however, it is commonly assumed that scattering lengths must be much smaller than all system dimensions and all absorption lengths for the approximation to be accurate. Neither of these conditions is satisfied in the cerebrospinal fluid (CSF). Since line-of-sight distances in the CSF are small, of the order of a few millimeters, we explore the idea that the CSF scattering coefficient may be modeled by any value from zero up to the order of the typical inverse line-of-sight distance, or approximately 0.3 mm-1, without significantly altering the calculated detector signals or the partial path lengths relevant for functional measurements. We demonstrate this in detail by using a Monte Carlo simulation of the RTE in a three-dimensional head model based on clinical magnetic resonance imaging data, with realistic optode geometries. Our findings lead us to expect that the diffusion approximation will be valid even in the presence of the CSF, with consequences for faster solution of the inverse problem.

SU-F-T-504: Non-Divergent Planning Method for Craniospinal Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sperling, N; Bogue, J; Parsai, E

2016-06-15

Purpose: Traditional Craniospinal Irradiation (CSI) planning techniques require careful field placement to allow optimal divergence and field overlap at depth, and measurement of skin gap. The result of this is a necessary field overlap resulting in dose heterogeneity in the spinal canal. A novel, nondivergent field matching method has been developed to allow simple treatment planning and delivery without the need to measure skin gap. Methods: The CSI patient was simulated in the prone, and a plan was developed. Bilateral cranial fields were designed with couch and collimator rotation to eliminate divergence with the upper spine field and minimize anteriormore » divergence into the lenses. Spinal posterior-to-anterior fields were designed with the couch rotated to 90 degrees to allow gantry rotation to eliminate divergence at the match line, and the collimator rotated to 90 degrees to allow appropriate field blocking with the MLCs. A match line for the two spinal fields was placed and the gantry rotated to equal angles in opposite directions about the match line. Jaw positions were then defined to allow 1mm overlap at the match line to avoid cold spots. A traditional CSI plan was generated using diverging spinal fields, and a comparison between the two techniques was generated. Results: The non-divergent treatment plan was able to deliver a highly uniform dose to the spinal cord with a cold spot of only 95% and maximum point dose of 115.8%, as compared to traditional plan cold spots of 87% and hot spots of 132% of the prescription dose. Conclusion: A non-divergent method for planning CSI patients has been developed and clinically implemented. Planning requires some geometric manipulation in order to achieve an adequate dose distribution, however, it can help to manage cold spots and simplify the shifts needed between spinal fields.« less

A novel supine isocentric approach for craniospinal irradiation and its clinical outcome.

PubMed

Cheng, Yi-Kan; Zeng, Lei; Ye, Shu-Biao; Zheng, Jian; Zhang, Lin; Sun, Peng; Jiang, Xiao-Bo; Sun, Wen-Zhao; Xu, Tao; Chen, Lei

2016-09-01

To report a novel approach for craniospinal irradiation (CSI) using a supine isocentric technique. Patients were treated in the supine position using CT simulation. Half-beam-blocked lateral cranial fields and superior spinal fields have the same isocentre, and their beam divergences match. Tangential irradiation provides a non-divergent junction for the other two full-beam spinal fields. Shielding for cranial fields was generated, and dose distribution was calculated using a three-dimensional planning system. When sacral spinal fields were required, two lateral opposite fields were designed to protect the urogenital organs. All treatment portals were filmed once per week. At a median follow-up of 49.8 months, 5 relapses and no cases of radiation myelitis developed in 26 consecutive patients. In the junctions of the brain-spine or spine-spine field, no failure occurred. Three failures occurred in the primary site alone, two in the spinal axis alone. The results of our study have shown that our novel approach for CSI was not associated with increased failures at the field junction and deaths. In addition, no radiation myelitis, pneumonia, severe damage to the heart and gastrointestinal tract, and second cancers occurred in our study. This new approach is an optimal alternative in cancer centre without tomotherapy because of its convenience for immobilization, repeatability, optimal dose distribution and satisfactory clinical outcome.

Restoration of motor function after operative reconstruction of the acutely transected spinal cord in the canine model.

PubMed

Liu, Zehan; Ren, Shuai; Fu, Kuang; Wu, Qiong; Wu, Jun; Hou, Liting; Pan, Hong; Sun, Linlin; Zhang, Jian; Wang, Bingjian; Miao, Qing; Sun, Guiyin; Bonicalzi, Vincenzo; Canavero, Sergio; Ren, Xiaoping

2018-05-01

Cephalosomatic anastomosis or what has been called a "head transplantation" requires full reconnection of the respective transected ends of the spinal cords. The GEMINI spinal cord fusion protocol has been developed for this reason. Here, we report the first randomized, controlled study of the GEMINI protocol in large animals. We conducted a randomized, controlled study of a complete transection of the spinal cord at the level of T10 in dogs at Harbin Medical University, Harbin, China. These dogs were followed for up to 8 weeks postoperatively by assessments of recovery of motor function, somato-sensory evoked potentials, and diffusion tensor imaging using magnetic resonance imaging. A total of 12 dogs were subjected to operative exposure of the dorsal aspect of the spinal cord after laminectomy and longitudinal durotomy followed by a very sharp, controlled, full-thickness, complete transection of the spinal cord at T10. The fusogen, polyethylene glycol, was applied topically to the site of the spinal cord transection in 7 of 12 dogs; 0.9% NaCl saline was applied to the site of transection in the remaining 5 control dogs. Dogs were selected randomly to receive polyethylene glycol or saline. All polyethylene glycol-treated dogs reacquired a substantial amount of motor function versus none in controls over these first 2 months as assessed on the 20-point (0-19), canine, Basso-Beattie-Bresnahan rating scale (P<.006). Somatosensory evoked potentials confirmed restoration of electrical conduction cranially across the site of spinal cord transection which improved over time. Diffusion tensor imaging, a magnetic resonance permutation that assesses the integrity of nerve fibers and cells, showed restitution of the transected spinal cord with polyethylene glycol treatment (at-injury level difference: P<.02). A sharply and fully transected spinal cord at the level of T10 can be reconstructed with restoration of many aspects of electrical continuity in large animals following the GEMINI spinal cord fusion protocol, with objective evidence of motor recovery and of electrical continuity across the site of transection, opening the way to the first cephalosomatic anastomosis. (Surgery 2017;160:XXX-XXX.). Copyright © 2017. Published by Elsevier Inc.

Combining neuroprotective agents: effect of riluzole and magnesium in a rat model of thoracic spinal cord injury.

PubMed

Vasconcelos, Natália L; Gomes, Eduardo D; Oliveira, Eduarda P; Silva, Carlos J; Lima, Rui; Sousa, Nuno; Salgado, António J; Silva, Nuno A

2016-08-01

Damage to the spinal cord can result in irreversible impairments or complete loss of motor, sensory, and autonomic functions. Riluzole and magnesium have been widely investigated as neuroprotective agents in animal models of spinal cord injury. As these drugs protect the injured spinal cord through different mechanisms, we aimed to investigate if their neuroprotective efficacy could be cumulative. This study aimed to investigate the neuroprotective efficacy of combined administration of riluzole and magnesium chloride in a contusive model of thoracic spinal cord injury. An in vivo experiment was set using female Wistar Han rats that underwent a thoracic spinal cord contusion (T8) using a weight drop method. An hour after injury, animals were randomly distributed to receive (1) saline, (2) riluzole (2.50 mg/kg), (3) magnesium chloride (24.18 mg/kg) in a polyethylene glycol formulation, or (4) a combined treatment (riluzole and magnesium). Subsequent treatments were given in four intraperitoneal injections (spaced 12 hours apart). The Basso, Beattie, and Bresnahan locomotor rating scale, an activity box test, and a swimming test were used to evaluate behavioral recovery over a 4-week period. Histologic analysis of the spinal cords was performed to measure the extent and volume of the lesion, axonal preservation, serotonergic and glutamatergic fiber sparing, motor neuron survival, and inflammation. Our results show that only the riluzole treatment significantly improved behavioral recovery up to 4 weeks after injury when compared with saline controls (6.2±1.8), with animals achieving weight-supported stepping (9.1±1.2). Riluzole also promoted tissue sparing with significant differences achieved from 200 to 600 µm (caudally to the lesion epicenter), and reduced lesion volume, with animals presenting a significantly smaller lesion (3.23±0.26 mm(3)) when compared with the saline-treated group (4.74±0.80 mm(3)), representing a 32% decrease in lesion volume. Riluzole treatment induced significant axonal preservation, as well as serotonergic fiber sparing, caudally to the injury epicenter. Our results suggest that the combined treatment, although simultaneously targeting two excitotoxic-related mechanisms, did not further improve behavioral and histologic outcome when compared with riluzole given alone. Copyright © 2016 Elsevier Inc. All rights reserved.

The personal and national costs of early retirement because of spinal disorders: impacts on income, taxes, and government support payments.

PubMed

Schofield, Deborah J; Shrestha, Rupendra N; Percival, Richard; Passey, Megan E; Callander, Emily J; Kelly, Simon J

2012-12-01

Spinal disorders can reduce an individual's ability to participate in the labor force, and this can lead to considerable impacts on both the individual and the state. This study was aimed to quantify the personal cost of lost income and the cost to the state from lost income taxation, increased benefits payments, and lost gross domestic product (GDP) as a result of early retirement because of spinal disorders in Australians aged 45 to 64 years in 2009. This was done using cross-sectional analysis of the base population of Health&WealthMOD, a microsimulation model built on data from the Australian Bureau of Statistics' Survey of Disability, Ageing and Carers, and STINMOD, an income and savings microsimulation model. Linear regression models were used to examine the relationship between spinal disorders, labor force participation, income, taxation, and government support payments. It was found that individuals aged 45 to 64 years who have retired early because of spinal disorders have significantly lower income (79% less; 95% confidence interval [CI], -84.7, -71.1; p<.0001), pay significantly less taxation (100% less; 95% CI, -100.0, 99.9; p<.0001), and receive significantly more in government support payments (21,000% more; 95% CI, 12,767.0, 35,336.4; p<.0001) than those employed full time with no health condition. Individuals who have retired early because of spinal disorders have a median value of total weekly income of only AU$310, whereas those who are employed full time are likely to receive four times this. This has a large national aggregate impact, with AU$4.8 billion lost in annual individual earnings, AU$622 million in additional welfare payments, AU$497 million lost in taxation revenue for governments, and AU$2.9 billion in lost GDP: all attributable to spinal disorders through their impact on labor force participation. Although the individual has to bear the economic costs of lost income in addition to the burden of the condition itself, the state experiences the impacts of loss of productivity from reduced workforce participation, lost income taxation revenue, and increasing government support payments. Copyright © 2012 Elsevier Inc. All rights reserved.

Tribology of flexible and sliding spinal implants: Development of experimental and numerical models.

PubMed

Le Cann, Sophie; Chaves-Jacob, Julien; Rossi, Jean-Marie; Linares, Jean-Marc; Chabrand, Patrick

2018-01-01

New fusionless devices are being developed to get over the limits of actual spinal surgical treatment, based on arthrodesis. However, due to their recentness, no standards exist to test and validate those devices, especially concerning the wear. A new tribological first approach to the definition of an in vitro wear protocol to study wear of flexible and sliding spinal devices is presented in this article, and was applied to a new concept. A simplified synthetic spine portion (polyethylene) was developed to reproduce a simple supra-physiological spinal flexion (10° between two vertebrae). The device studied with this protocol was tested in wet environment until 1 million cycles (Mc). We obtained an encouraging estimated wear volume of same order of magnitude compared to similar devices. An associated finite element (FE) numerical model has permitted to access contact information and study the effect of misalignment of one screw. First results could point out how to improve the design and suggest that a vertical misalignment of a screw (under or over-screwing) has more impact than a horizontal one. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 104-111, 2018. © 2016 Wiley Periodicals, Inc.

Spinal lordosis optimizes the requirements for a stable erect posture.

PubMed

Wagner, Heiko; Liebetrau, Anne; Schinowski, David; Wulf, Thomas; de Lussanet, Marc H E

2012-04-16

Lordosis is the bending of the lumbar spine that gives the vertebral column of humans its characteristic ventrally convex curvature. Infants develop lordosis around the time when they acquire bipedal locomotion. Even macaques develop a lordosis when they are trained to walk bipedally. The aim of this study was to investigate why humans and some animals develop a lumbar lordosis while learning to walk bipedally. We developed a musculoskeletal model of the lumbar spine, that includes an asymmetric, dorsally shifted location of the spinal column in the body, realistic moment arms, and physiological cross-sectional areas (PCSA) of the muscles as well as realistic force-length and force-velocity relationships. The model was used to analyze the stability of an upright body posture. According to our results, lordosis reduces the local joint torques necessary for an equilibrium of the vertebral column during an erect posture. At the same time lordosis increases the demands on the global muscles to provide stability. We conclude that the development of a spinal lordosis is a compromise between the stability requirements of an erect posture and the necessity of torque equilibria at each spinal segment.

Spinal lordosis optimizes the requirements for a stable erect posture

PubMed Central

2012-01-01

Background Lordosis is the bending of the lumbar spine that gives the vertebral column of humans its characteristic ventrally convex curvature. Infants develop lordosis around the time when they acquire bipedal locomotion. Even macaques develop a lordosis when they are trained to walk bipedally. The aim of this study was to investigate why humans and some animals develop a lumbar lordosis while learning to walk bipedally. Results We developed a musculoskeletal model of the lumbar spine, that includes an asymmetric, dorsally shifted location of the spinal column in the body, realistic moment arms, and physiological cross-sectional areas (PCSA) of the muscles as well as realistic force-length and force-velocity relationships. The model was used to analyze the stability of an upright body posture. According to our results, lordosis reduces the local joint torques necessary for an equilibrium of the vertebral column during an erect posture. At the same time lordosis increases the demands on the global muscles to provide stability. Conclusions We conclude that the development of a spinal lordosis is a compromise between the stability requirements of an erect posture and the necessity of torque equilibria at each spinal segment. PMID:22507595

Effects of spinal cord injury-induced changes in muscle activation on foot drag in a computational rat ankle model

PubMed Central

Hillen, Brian K.; Jindrich, Devin L.; Abbas, James J.; Yamaguchi, Gary T.

2015-01-01

Spinal cord injury (SCI) can lead to changes in muscle activation patterns and atrophy of affected muscles. Moderate levels of SCI are typically associated with foot drag during the swing phase of locomotion. Foot drag is often used to assess locomotor recovery, but the causes remain unclear. We hypothesized that foot drag results from inappropriate muscle coordination preventing flexion at the stance-to-swing transition. To test this hypothesis and to assess the relative contributions of neural and muscular changes on foot drag, we developed a two-dimensional, one degree of freedom ankle musculoskeletal model with gastrocnemius and tibialis anterior muscles. Anatomical data collected from sham-injured and incomplete SCI (iSCI) female Long-Evans rats as well as physiological data from the literature were used to implement an open-loop muscle dynamics model. Muscle insertion point motion was calculated with imposed ankle trajectories from kinematic analysis of treadmill walking in sham-injured and iSCI animals. Relative gastrocnemius deactivation and tibialis anterior activation onset times were varied within physiologically relevant ranges based on simplified locomotor electromyogram profiles. No-atrophy and moderate muscle atrophy as well as normal and injured muscle activation profiles were also simulated. Positive moments coinciding with the transition from stance to swing phase were defined as foot swing and negative moments as foot drag. Whereas decreases in activation delay caused by delayed gastrocnemius deactivation promote foot drag, all other changes associated with iSCI facilitate foot swing. Our results suggest that even small changes in the ability to precisely deactivate the gastrocnemius could result in foot drag after iSCI. PMID:25673734

Effects of spinal cord injury-induced changes in muscle activation on foot drag in a computational rat ankle model.

PubMed

Hillen, Brian K; Jindrich, Devin L; Abbas, James J; Yamaguchi, Gary T; Jung, Ranu

2015-04-01

Spinal cord injury (SCI) can lead to changes in muscle activation patterns and atrophy of affected muscles. Moderate levels of SCI are typically associated with foot drag during the swing phase of locomotion. Foot drag is often used to assess locomotor recovery, but the causes remain unclear. We hypothesized that foot drag results from inappropriate muscle coordination preventing flexion at the stance-to-swing transition. To test this hypothesis and to assess the relative contributions of neural and muscular changes on foot drag, we developed a two-dimensional, one degree of freedom ankle musculoskeletal model with gastrocnemius and tibialis anterior muscles. Anatomical data collected from sham-injured and incomplete SCI (iSCI) female Long-Evans rats as well as physiological data from the literature were used to implement an open-loop muscle dynamics model. Muscle insertion point motion was calculated with imposed ankle trajectories from kinematic analysis of treadmill walking in sham-injured and iSCI animals. Relative gastrocnemius deactivation and tibialis anterior activation onset times were varied within physiologically relevant ranges based on simplified locomotor electromyogram profiles. No-atrophy and moderate muscle atrophy as well as normal and injured muscle activation profiles were also simulated. Positive moments coinciding with the transition from stance to swing phase were defined as foot swing and negative moments as foot drag. Whereas decreases in activation delay caused by delayed gastrocnemius deactivation promote foot drag, all other changes associated with iSCI facilitate foot swing. Our results suggest that even small changes in the ability to precisely deactivate the gastrocnemius could result in foot drag after iSCI. Copyright © 2015 the American Physiological Society.

Radiobiological evaluation of simultaneously dose-escalated versus non-escalated intensity-modulated radiation therapy for patients with upper thoracic esophageal cancer.

PubMed

Huang, Bao-Tian; Wu, Li-Li; Guo, Long-Jia; Xu, Liang-Yu; Huang, Rui-Hong; Lin, Pei-Xian; Chen, Jian-Zhou; Li, De-Rui; Chen, Chuang-Zhen

2017-01-01

To compare the radiobiological response between simultaneously dose-escalated and non-escalated intensity-modulated radiation therapy (DE-IMRT and NE-IMRT) for patients with upper thoracic esophageal cancer (UTEC) using radiobiological evaluation. Computed tomography simulation data sets for 25 patients pathologically diagnosed with primary UTEC were used in this study. DE-IMRT plan with an escalated dose of 64.8 Gy/28 fractions to the gross tumor volume (GTV) and involved lymph nodes from 25 patients pathologically diagnosed with primary UTEC, was compared to an NE-IMRT plan of 50.4 Gy/28 fractions. Dose-volume metrics, tumor control probability (TCP), and normal tissue complication probability for the lung and spinal cord were compared. In addition, the risk of acute esophageal toxicity (AET) and late esophageal toxicity (LET) were also analyzed. Compared with NE-IMRT plan, we found the DE-IMRT plan resulted in a 14.6 Gy dose escalation to the GTV. The tumor control was predicted to increase by 31.8%, 39.1%, and 40.9% for three independent TCP models. The predicted incidence of radiation pneumonitis was similar (3.9% versus 3.6%), and the estimated risk of radiation-induced spinal cord injury was extremely low (<0.13%) in both groups. Regarding the esophageal toxicities, the estimated grade ≥2 and grade ≥3 AET predicted by the Kwint model were increased by 2.5% and 3.8%. Grade ≥2 AET predicted using the Wijsman model was increased by 14.9%. The predicted incidence of LET was low (<0.51%) in both groups. Radiobiological evaluation reveals that the DE-IMRT dosing strategy is feasible for patients with UTEC, with significant gains in tumor control and minor or clinically acceptable increases in radiation-induced toxicities.

Cancer pain physiology

PubMed Central

Falk, Sarah; Bannister, Kirsty

2014-01-01

Mechanisms of inflammatory and neuropathic pains have been elucidated and translated to patient care by the use of animal models of these pain states. Cancer pain has lagged behind since early animal models of cancer-induced bone pain were based on the systemic injection of carcinoma cells. This precluded systematic investigation of specific neuronal and pharmacological alterations that occur in cancer-induced bone pain. In 1999, Schwei et al. described a murine model of cancer-induced bone pain that paralleled the clinical condition in terms of pain development and bone destruction, confined to the mouse femur. This model prompted related approaches, and we can now state that cancer pain may include elements of inflammatory and neuropathic pains but also unique changes in sensory processing. Cancer-induced bone pain results in progressive bone destruction, elevated osteoclast activity and distinctive nocifensive behaviours (indicating the triad of ongoing, spontaneous and movement-induced hyperalgesia). In addition, cancer cells induce an inflammatory infiltrate and release growth factors, cytokines, interleukins, chemokines, prostanoids and endothelins, resulting in a reduction of pH to below 5 and direct deformation of primary afferents within bone. These peripheral changes, in turn, drive hypersensitivity of spinal cord sensory neurons, many of which project to the parts of the brain involved in the emotional response to pain. Within the spinal cord, a unique neuronal function reorganization within segments of the dorsal horn of the spinal cord receiving nociceptive input from the bone are discussed. Changes in certain neurotransmitters implicated in brain modulation of spinal function are also altered with implications for the affective components of cancer pain. Treatments are described in terms of mechanistic insights and in the case of opioids, which modulate pain transmission at spinal and supraspinal sites, their use can be compromised by opioid-induced hyperalgesia. We discuss evidence for how this comes about and how it may be treated. PMID:26516549

Attenuation of inflammatory and neuropathic pain behaviors in mice through activation of free fatty acid receptor GPR40.

PubMed

Karki, Prasanna; Kurihara, Takashi; Nakamachi, Tomoya; Watanabe, Jun; Asada, Toshihide; Oyoshi, Tatsuki; Shioda, Seiji; Yoshimura, Megumu; Arita, Kazunori; Miyata, Atsuro

2015-02-12

The G-protein-coupled receptor 40 (GPR40) is suggested to function as a transmembrane receptor for medium- to long-chain free fatty acids and is implicated to play a role in free fatty acids-mediated enhancement of glucose-stimulated insulin secretion from pancreas. However, the functional role of GPR40 in nervous system including somatosensory pain signaling has not been fully examined yet. Intrathecal injection of GPR40 agonist (MEDICA16 or GW9508) dose-dependently reduced ipsilateral mechanical allodynia in CFA and SNL models and thermal hyperalgesia in carrageenan model. These anti-allodynic and anti-hyperalgesic effects were almost completely reversed by a GPR40 antagonist, GW1100. Immunohistochemical analysis revealed that GPR40 is expressed in spinal dorsal horn and dorsal root ganglion neurons, and immunoblot analysis showed that carrageenan or CFA inflammation or spinal nerve injury resulted in increased expression of GPR40 in these areas. Patch-clamp recordings from spinal cord slices exhibited that bath-application of either MEDICA16 or GW9508 significantly decreased the frequency of spontaneous excitatory postsynaptic currents in the substantia gelatinosa neurons of the three pain models. Our results indicate that GPR40 signaling pathway plays an important suppressive role in spinal nociceptive processing after inflammation or nerve injury, and that GPR40 agonists might serve as a new class of analgesics for treating inflammatory and neuropathic pain.

A Perturbed MicroRNA Expression Pattern Characterizes Embryonic Neural Stem Cells Derived from a Severe Mouse Model of Spinal Muscular Atrophy (SMA)

PubMed Central

Luchetti, Andrea; Ciafrè, Silvia Anna; Murdocca, Michela; Malgieri, Arianna; Masotti, Andrea; Sanchez, Massimo; Farace, Maria Giulia; Novelli, Giuseppe; Sangiuolo, Federica

2015-01-01

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs) derived from embryonic spinal cords of a severe SMNΔ7 SMA mouse model. SMNΔ7 NSCs behave as their wild type (WT) counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNΔ7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNΔ7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNΔ7 NSCs, and may be potentially involved in the molecular mechanisms of SMA. PMID:26258776

A Perturbed MicroRNA Expression Pattern Characterizes Embryonic Neural Stem Cells Derived from a Severe Mouse Model of Spinal Muscular Atrophy (SMA).

PubMed

Luchetti, Andrea; Ciafrè, Silvia Anna; Murdocca, Michela; Malgieri, Arianna; Masotti, Andrea; Sanchez, Massimo; Farace, Maria Giulia; Novelli, Giuseppe; Sangiuolo, Federica

2015-08-06

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs) derived from embryonic spinal cords of a severe SMNΔ7 SMA mouse model. SMNΔ7 NSCs behave as their wild type (WT) counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNΔ7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNΔ7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNΔ7 NSCs, and may be potentially involved in the molecular mechanisms of SMA.

A model-based exploration of the role of pattern generating circuits during locomotor adaptation.

PubMed

Marjaninejad, Ali; Finley, James M

2016-08-01

In this study, we used a model-based approach to explore the potential contributions of central pattern generating circuits (CPGs) during adaptation to external perturbations during locomotion. We constructed a neuromechanical modeled of locomotion using a reduced-phase CPG controller and an inverted pendulum mechanical model. Two different forms of locomotor adaptation were examined in this study: split-belt treadmill adaptation and adaptation to a unilateral, elastic force field. For each simulation, we first examined the effects of phase resetting and varying the model's initial conditions on the resulting adaptation. After evaluating the effect of phase resetting on the adaptation of step length symmetry, we examined the extent to which the results from these simple models could explain previous experimental observations. We found that adaptation of step length symmetry during split-belt treadmill walking could be reproduced using our model, but this model failed to replicate patterns of adaptation observed in response to force field perturbations. Given that spinal animal models can adapt to both of these types of perturbations, our findings suggest that there may be distinct features of pattern generating circuits that mediate each form of adaptation.

Worklife After Traumatic Spinal Cord Injury

PubMed Central

Pflaum, Christopher; McCollister, George; Strauss, David J; Shavelle, Robert M; DeVivo, Michael J

2006-01-01

Objective: To develop predictive models to estimate worklife expectancy after spinal cord injury (SCI). Design: Inception cohort study. Setting: Model SCI Care Systems throughout the United States. Participants: 20,143 persons enrolled in the National Spinal Cord Injury Statistical Center database since 1973. Intervention: Not applicable. Main Outcome Measure: Postinjury employment rates and worklife expectancy. Results: Using logistic regression, we found a greater likelihood of being employed in any given year to be significantly associated with younger age, white race, higher education level, being married, having a nonviolent cause of injury, paraplegia, ASIA D injury, longer time postinjury, being employed at injury and during the previous postinjury year, higher general population employment rate, lower level of Social Security Disability Insurance benefits, and calendar years after the passage of the Americans with Disabilities Act. Conclusions: The likelihood of postinjury employment varies substantially among persons with SCI. Given favorable patient characteristics, worklife should be considerably higher than previous estimates. PMID:17044388

Valproic acid improves locomotion in vivo after SCI and axonal growth of neurons in vitro.

PubMed

Lv, Lei; Han, Xiang; Sun, Yan; Wang, Xin; Dong, Qiang

2012-02-01

Previous studies have found that valproic acid (VPA), a histone deacetylases (HDAC) inhibitor, improves outcomes in a rat model of spinal cord injury (SCI). The study here aimed to further illuminate the neuroprotective effects of VPA against SCI, both in vivo and in vitro. First, spinal cord injury was performed in rats using NYU impactor. Delayed VPA injection (8 h following SCI) significantly accelerated locomotor recovery. VPA therapy also suppressed SCI-induced hypoacetylation of histone and promoted expressions of BDNF and GDNF. Next, the influence of VPA on axonal growth inhibited by a myelin protein was tested. Neurons from embryonic spinal cord or hippocampus were cultured on plates coated with Nogo-A peptide, and escalating concentrations of VPA were added into the cultures. VPA treatment, in a concentration dependent manner, allowed neurons to overcome Nogo-A inhibition of neurite outgrowth. Meanwhile, VPA exposure increased the level of histone acetylation and expression of BDNF in spinal neurons. Cumulatively, these findings indicate that VPA is possibly a promising medication and deserves translational trials for spinal cord injury. Copyright © 2011 Elsevier Inc. All rights reserved.

Closed-loop neuromodulation of spinal sensorimotor circuits controls refined locomotion after complete spinal cord injury.

PubMed

Wenger, Nikolaus; Moraud, Eduardo Martin; Raspopovic, Stanisa; Bonizzato, Marco; DiGiovanna, Jack; Musienko, Pavel; Morari, Manfred; Micera, Silvestro; Courtine, Grégoire

2014-09-24

Neuromodulation of spinal sensorimotor circuits improves motor control in animal models and humans with spinal cord injury. With common neuromodulation devices, electrical stimulation parameters are tuned manually and remain constant during movement. We developed a mechanistic framework to optimize neuromodulation in real time to achieve high-fidelity control of leg kinematics during locomotion in rats. We first uncovered relationships between neuromodulation parameters and recruitment of distinct sensorimotor circuits, resulting in predictive adjustments of leg kinematics. Second, we established a technological platform with embedded control policies that integrated robust movement feedback and feed-forward control loops in real time. These developments allowed us to conceive a neuroprosthetic system that controlled a broad range of foot trajectories during continuous locomotion in paralyzed rats. Animals with complete spinal cord injury performed more than 1000 successive steps without failure, and were able to climb staircases of various heights and lengths with precision and fluidity. Beyond therapeutic potential, these findings provide a conceptual and technical framework to personalize neuromodulation treatments for other neurological disorders. Copyright © 2014, American Association for the Advancement of Science.

Interfacing peripheral nerve with macro-sieve electrodes following spinal cord injury.

PubMed

Birenbaum, Nathan K; MacEwan, Matthew R; Ray, Wilson Z

2017-06-01

Macro-sieve electrodes were implanted in the sciatic nerve of five adult male Lewis rats following spinal cord injury to assess the ability of the macro-sieve electrode to interface regenerated peripheral nerve fibers post-spinal cord injury. Each spinal cord injury was performed via right lateral hemisection of the cord at the T 9-10 site. Five months post-implantation, the ability of the macro-sieve electrode to interface the regenerated nerve was assessed by stimulating through the macro-sieve electrode and recording both electromyography signals and evoked muscle force from distal musculature. Electromyography measurements were recorded from the tibialis anterior and gastrocnemius muscles, while evoked muscle force measurements were recorded from the tibialis anterior, extensor digitorum longus, and gastrocnemius muscles. The macro-sieve electrode and regenerated sciatic nerve were then explanted for histological evaluation. Successful sciatic nerve regeneration across the macro-sieve electrode interface following spinal cord injury was seen in all five animals. Recorded electromyography signals and muscle force recordings obtained through macro-sieve electrode stimulation confirm the ability of the macro-sieve electrode to successfully recruit distal musculature in this injury model. Taken together, these results demonstrate the macro-sieve electrode as a viable interface for peripheral nerve stimulation in the context of spinal cord injury.

Somatic genital reflexes in rats with a nod to humans: anatomy, physiology, and the role of the social neuropeptides

PubMed Central

Normandin, Joseph J.; Murphy, Anne Z.

2011-01-01

Somatic genital reflexes such as ejaculation and vaginocervical contractions are produced through the striated muscles associated with the genitalia. The coordination of these reflexes is surprisingly complex and involves a number of lumbosacral spinal and supraspinal systems. The rat model has proved to be an excellent source of information regarding these mechanisms, and many parallels to research in humans can be drawn. An understanding of the spinal systems involving the lumbosacral spinal cord, both efferent and afferent, has been generated through decades of research. Spinal and supraspinal mechanisms of descending excitation, through a spinal ejaculation generator in the lumbar spinal cord and thalamus, and descending inhibition, through the ventrolateral medulla, have been identified and characterized both anatomically and physiologically. In addition, delineation of the neural circuits whereby ascending genitosensory information regarding the regulation of somatic genital reflexes is relayed supraspinally has also been the topic of recent investigation. Lastly, the importance of the “social neuropeptides” oxytocin and vasopressin in the regulation of somatic genital reflexes, and associated sociosexual behaviors, is emerging. This work not only has implications for understanding how nervous systems generate sexual behavior, but also provides treatment targets for sexual dysfunction in people. PMID:21338605

Melatonin Inhibits Neural Cell Apoptosis and Promotes Locomotor Recovery via Activation of the Wnt/β-Catenin Signaling Pathway After Spinal Cord Injury.

PubMed

Shen, Zhaoliang; Zhou, Zipeng; Gao, Shuang; Guo, Yue; Gao, Kai; Wang, Haoyu; Dang, Xiaoqian

2017-08-01

The spinal cord is highly sensitive to spinal cord injury (SCI) by external mechanical damage, resulting in irreversible neurological damage. Activation of the Wnt/β-catenin signaling pathway can effectively reduce apoptosis and protect against SCI. Melatonin, an indoleamine originally isolated from bovine pineal tissue, exerts neuroprotective effects after SCI through activation of the Wnt/β-catenin signaling pathway. In this study, we demonstrated that melatonin exhibited neuroprotective effects on neuronal apoptosis and supported functional recovery in a rat SCI model by activating the Wnt/β-catenin signaling pathway. We found that melatonin administration after SCI significantly upregulated the expression of low-density lipoprotein receptor related protein 6 phosphorylation (p-LRP-6), lymphoid enhancer factor-1 (LEF-1) and β-catenin protein in the spinal cord. Melatonin enhanced motor neuronal survival in the spinal cord ventral horn and improved the locomotor functions of rats after SCI. Melatonin administration after SCI also reduced the expression levels of Bax and cleaved caspase-3 in the spinal cord and the proportion of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) positive cells, but increased the expression level of Bcl-2. These results suggest that melatonin attenuated SCI by activating the Wnt/β-catenin signaling pathway.

Induction of Parkinson disease-related proteins in motor neurons after transient spinal cord ischemia in rabbits.

PubMed

Sakurai, Masahiro; Kawamura, Takae; Nishimura, Hidekazu; Suzuki, Hiroyoshi; Tezuka, Fumiaki; Abe, Koji

2009-04-01

The mechanism of spinal cord injury has been thought to be related to the vulnerability of spinal motor neuron cells against ischemia. However, the mechanisms of such vulnerability are not fully understood. We investigated a possible mechanism of neuronal death by immunohistochemical analysis for DJ-1, PINK1, and alpha-Synuclein. We used a 15-min rabbit spinal cord ischemia model, with use of a balloon catheter. Western blot analysis for DJ-1, PINK1, and alpha-Synuclein; temporal profiles of DJ-1, PINK1, and alpha-Synuclein immunoreactivity; and double-label fluorescence immunocytochemical studies were performed. Western blot analysis revealed scarce immunoreactivity for DJ-1, PINK1, and alpha-Synuclein in the sham-operated spinal cords. However, they became apparent at 8 h after transient ischemia, which returned to the baseline level at 1 day. Double-label fluorescence immunocytochemical study revealed that both DJ-1 and PINK1, and DJ-1 and alpha-Synuclein were positive at 8 h of reperfusion in the same motor neurons, which eventually die. The induction of DJ-1 and PINK1 proteins in the motor neurons at the early stage of reperfusion may indicate oxidative stress, and the induction of alpha-Synuclein may be implicated in the programmed cell death change after transient spinal cord ischemia.

Automated quantitative gait analysis during overground locomotion in the rat: its application to spinal cord contusion and transection injuries.

PubMed

Hamers, F P; Lankhorst, A J; van Laar, T J; Veldhuis, W B; Gispen, W H

2001-02-01

Analysis of locomotion is an important tool in the study of peripheral and central nervous system damage. Most locomotor scoring systems in rodents are based either upon open field locomotion assessment, for example, the BBB score or upon foot print analysis. The former yields a semiquantitative description of locomotion as a whole, whereas the latter generates quantitative data on several selected gait parameters. In this paper, we describe the use of a newly developed gait analysis method that allows easy quantitation of a large number of locomotion parameters during walkway crossing. We were able to extract data on interlimb coordination, swing duration, paw print areas (total over stance, and at 20-msec time resolution), stride length, and base of support: Similar data can not be gathered by any single previously described method. We compare changes in gait parameters induced by two different models of spinal cord injury in rats, transection of the dorsal half of the spinal cord and spinal cord contusion injury induced by the NYU or MASCIS device. Although we applied this method to rats with spinal cord injury, the usefulness of this method is not limited to rats or to the investigation of spinal cord injuries alone.

A comparison of the effects of epidural and spinal anesthesia with ischemia-reperfusion injury on the rat transverse rectus abdominis musculocutaneous flap.

PubMed

Acar, Yusuf; Bozkurt, Mehmet; Firat, Ugur; Selcuk, Caferi Tayyar; Kapi, Emin; Isik, Fatma Birgul; Kuvat, Samet Vasfi; Celik, Feyzi; Bozarslan, Beri Hocaoglu

2013-11-01

The purpose of this study is to compare the effects of spinal and epidural anesthesia on a rat transverse rectus abdominus myocutaneous flap ischemia-reperfusion injury model.Forty Sprague-Dawley rats were divided into 4 experimental groups: group I (n = 10), sham group; group II (n = 10), control group; group III (n = 10), epidural group; and group IV (n = 10), spinal group. After the elevation of the transverse rectus abdominus myocutaneous flaps, all groups except for the sham group were subjected to normothermic no-flow ischemia for 4 hours, followed by a reperfusion period of 2 hours. At the end of the reperfusion period, biochemical and histopathological evaluations were performed on tissue samples.Although there was no significant difference concerning the malonyldialdehyde, nitric oxide, and paraoxonase levels in the spinal and epidural groups, the total antioxidant state levels were significantly increased, and the total oxidative stress levels were significantly decreased in the epidural group in comparison to the spinal group. The pathological evaluation showed that findings related to inflammation, nuclear change rates and hyalinization were significantly higher in the spinal group compared with the epidural group.Epidural anesthesia can be considered as a more suitable method that enables a decrease in ischemia-reperfusion injuries in the muscle flaps.

Blood-Spinal Cord Barrier Alterations in Subacute and Chronic Stages of a Rat Model of Focal Cerebral Ischemia

PubMed Central

Haller, Edward; Tajiri, Naoki; Thomson, Avery; Barretta, Jennifer; Williams, Stephanie N.; Haim, Eithan D.; Qin, Hua; Frisina-Deyo, Aric; Abraham, Jerry V.; Sanberg, Paul R.; Van Loveren, Harry; Borlongan, Cesario V.

2016-01-01

We previously demonstrated blood-brain barrier impairment in remote contralateral brain areas in rats at 7 and 30 days after transient middle cerebral artery occlusion (tMCAO), indicating ischemic diaschisis. Here, we focused on effects of subacute and chronic focal cerebral ischemia on the blood-spinal cord barrier (BSCB). We observed BSCB damage on both sides of the cervical spinal cord in rats at 7 and 30 days post-tMCAO. Major BSCB ultrastructural changes in spinal cord gray and white matter included vacuolated endothelial cells containing autophagosomes, pericyte degeneration with enlarged mitochondria, astrocyte end-feet degeneration and perivascular edema; damaged motor neurons, swollen axons with unraveled myelin in ascending and descending tracts and astrogliosis were also observed. Evans Blue dye extravasation was maximal at 7 days. There was immunofluorescence evidence of reduction of microvascular expression of tight junction occludin, upregulation of Beclin-1 and LC3B immunoreactivities at 7 days and a reduction of the latter at 30 days post-ischemia. These novel pathological alterations on the cervical spinal cord microvasculature in rats after tMCAO suggest pervasive and long-lasting BSCB damage after focal cerebral ischemia, and that spinal cord ischemic diaschisis should be considered in the pathophysiology and therapeutic approaches in patients with ischemic cerebral infarction. PMID:27283328

The Lesioned Spinal Cord Is a “New” Spinal Cord: Evidence from Functional Changes after Spinal Injury in Lamprey

PubMed Central

Parker, David

2017-01-01

Finding a treatment for spinal cord injury (SCI) focuses on reconnecting the spinal cord by promoting regeneration across the lesion site. However, while regeneration is necessary for recovery, on its own it may not be sufficient. This presumably reflects the requirement for regenerated inputs to interact appropriately with the spinal cord, making sub-lesion network properties an additional influence on recovery. This review summarizes work we have done in the lamprey, a model system for SCI research. We have compared locomotor behavior (swimming) and the properties of descending inputs, locomotor networks, and sensory inputs in unlesioned animals and animals that have received complete spinal cord lesions. In the majority (∼90%) of animals swimming parameters after lesioning recovered to match those in unlesioned animals. Synaptic inputs from individual regenerated axons also matched the properties in unlesioned animals, although this was associated with changes in release parameters. This suggests against any compensation at these synapses for the reduced descending drive that will occur given that regeneration is always incomplete. Compensation instead seems to occur through diverse changes in cellular and synaptic properties in locomotor networks and proprioceptive systems below, but also above, the lesion site. Recovery of locomotor performance is thus not simply the reconnection of the two sides of the spinal cord, but reflects a distributed and varied range of spinal cord changes. While locomotor network changes are insufficient on their own for recovery, they may facilitate locomotor outputs by compensating for the reduction in descending drive. Potentiated sensory feedback may in turn be a necessary adaptation that monitors and adjusts the output from the “new” locomotor network. Rather than a single aspect, changes in different components of the motor system and their interactions may be needed after SCI. If these are general features, and where comparisons with mammalian systems can be made effects seem to be conserved, improving functional recovery in higher vertebrates will require interventions that generate the optimal spinal cord conditions conducive to recovery. The analyses needed to identify these conditions are difficult in the mammalian spinal cord, but lower vertebrate systems should help to identify the principles of the optimal spinal cord response to injury. PMID:29163065

Morphine amplifies mechanical allodynia via TLR4 in a rat model of spinal cord injury

PubMed Central

Ellis, Amanda; Grace, Peter M.; Wieseler, Julie; Favret, Jacob; Springer, Kendra; Skarda, Bryce; Hutchinson, Mark R.; Falci, Scott; Rice, Kenner C.; Maier, Steven F.; Watkins, Linda R.

2016-01-01

Central neuropathic pain (CNP) is a pervasive, debilitating problem that impacts thousands of people living with central nervous system disorders, including spinal cord injury (SCI). Current therapies for treating this type of pain are ineffective and often have dose-limiting side effects. Although opioids are one of the most commonly used CNP treatments, recent animal literature has indicated that administering opioids shortly after a traumatic injury can actually have deleterious effects on long-term health and recovery. In order to study the deleterious effects of administering morphine shortly after trauma, we employed our low thoracic (T13) dorsal root avulsion model (Spinal Neuropathic Avulsion Pain, SNAP). Administering a weeklong course of 10 mg/kg/day morphine beginning 24 hr after SNAP resulted in amplified mechanical allodynia. Co-administering the non-opioid toll-like receptor 4 (TLR4) antagonist (+)-naltrexone throughout the morphine regimen prevented morphine-induced amplification of SNAP. Exploration of changes induced by early post-trauma morphine revealed that this elevated gene expression of TLR4, TNF, IL-1β, and NLRP3, as well as IL-1β protein at the site of spinal cord injury. These data suggest that a short course of morphine administered early after spinal trauma can exacerbate CNP in the long term. TLR4 initiates this phenomenon and, as such, may be potential therapeutic targets for preventing the deleterious effects of administering opioids after traumatic injury. PMID:27519154

Antinociceptive interaction between spinal clonidine and lidocaine in the rat formalin test: an isobolographic analysis.

PubMed

Hao, S; Takahata, O; Iwasaki, H

2001-03-01

Clinical and basic science studies suggest that spinal alpha-2-adrenergic receptor agonists and local anesthetics produce analgesia, but interaction between alpha-2-adrenergic receptor agonists and local anesthetics in the persistent pain model has not been examined. In the present study, using isobolographic analysis, we investigated the antinociceptive interaction of intrathecal clonidine and lidocaine in the rat formalin test. Sprague-Dawley rats were implanted with chronic lumbar intrathecal catheters, and were tested for paw flinch by formalin injection. Biphasic painful behavior was counted. Intrathecal clonidine (3-12 nmol) was administered 15 min before formalin, and intrathecal lidocaine (375-1850 nmol) was administered 5 min before formalin. To examine the interaction of intrathecal clonidine and lidocaine, an isobolographic design was used. Spinal administration of clonidine produced dose-dependent suppression of the biphasic responses in the formalin test. Spinal lidocaine resulted in dose-dependent transient motor dysfunction and the motor dysfunction recovered to normal at 10-15 min after administration. Spinal lidocaine produced dose-dependent suppression of phase-2 activity in the formalin test. Isobolographic analysis showed that the combination of intrathecal clonidine and lidocaine synergistically reduced Phase-2 activity. We conclude that intrathecal clonidine synergistically interacts with lidocaine in reducing the nociceptive response in the formalin test. Preformalin administration of intrathecal clonidine and lidocaine dose-dependently produced antinociception in the formalin test. The combination of clonidine and lidocaine, synergistically produced suppression of nociceptive response in the persistent pain model.

Mitochondrial oxodicarboxylate carrier deficiency is associated with mitochondrial DNA depletion and spinal muscular atrophy-like disease.

PubMed

Boczonadi, Veronika; King, Martin S; Smith, Anthony C; Olahova, Monika; Bansagi, Boglarka; Roos, Andreas; Eyassu, Filmon; Borchers, Christoph; Ramesh, Venkateswaran; Lochmüller, Hanns; Polvikoski, Tuomo; Whittaker, Roger G; Pyle, Angela; Griffin, Helen; Taylor, Robert W; Chinnery, Patrick F; Robinson, Alan J; Kunji, Edmund R S; Horvath, Rita

2018-03-08

PurposeTo understand the role of the mitochondrial oxodicarboxylate carrier (SLC25A21) in the development of spinal muscular atrophy-like disease.MethodsWe identified a novel pathogenic variant in a patient by whole-exome sequencing. The pathogenicity of the mutation was studied by transport assays, computer modeling, followed by targeted metabolic testing and in vitro studies in human fibroblasts and neurons.ResultsThe patient carries a homozygous pathogenic variant c.695A>G; p.(Lys232Arg) in the SLC25A21 gene, encoding the mitochondrial oxodicarboxylate carrier, and developed spinal muscular atrophy and mitochondrial myopathy. Transport assays show that the mutation renders SLC25A21 dysfunctional and 2-oxoadipate cannot be imported into the mitochondrial matrix. Computer models of central metabolism predicted that impaired transport of oxodicarboxylate disrupts the pathways of lysine and tryptophan degradation, and causes accumulation of 2-oxoadipate, pipecolic acid, and quinolinic acid, which was confirmed in the patient's urine by targeted metabolomics. Exposure to 2-oxoadipate and quinolinic acid decreased the level of mitochondrial complexes in neuronal cells (SH-SY5Y) and induced apoptosis.ConclusionMitochondrial oxodicarboxylate carrier deficiency leads to mitochondrial dysfunction and the accumulation of oxoadipate and quinolinic acid, which in turn cause toxicity in spinal motor neurons leading to spinal muscular atrophy-like disease.GENETICS in MEDICINE advance online publication, 8 March 2018; doi:10.1038/gim.2017.251.

A computed tomographic anatomical study of the upper sacrum. Application for a user guide of pelvic fixation with iliosacral screws in adult spinal deformity.

PubMed

Dubory, Arnaud; Bouloussa, Houssam; Riouallon, Guillaume; Wolff, Stéphane

2017-12-01

Widely used in traumatic pelvic ring fractures, the iliosacral (IS) screw technique for spino-pelvic fixation remains anecdotal in adult spinal deformity. The objective of this study was to assess anatomical variability of the adult upper sacrum and to provide a user guide of spino-pelvic fixation with IS screws in adult spinal deformity. Anatomical variability of the upper sacrum according to age, gender, height and weight was sought on 30 consecutive pelvic CT-scans. Thus, a user guide of spino-pelvic fixation with IS screws was modeled and assessed on ten CT-scans as described below. Two invariable landmarks usable during the surgical procedure were defined: point A (corresponding to the connector binding the IS screw to the spinal rod), equidistant from the first posterior sacral hole and the base of the S1 articular facet and 10 mm-embedded into the sacrum; point B (corresponding to the tip of the IS screw) located at the junction of the anterior third and middle third of the sacral endplate in the sagittal plane and at the middle of the endplate in the coronal plane. Point C corresponded to the intersection between the A-B direction and the external facet of the iliac wing. Three-dimensional reconstructions modeling the IS screw optimal direction according to the A-B-C straight line were assessed. Age had no effect on the anatomy of the upper sacrum. The distance between the base of the S1 superior articular facet and the top of the first posterior sacral hole was correlated with weight (r = 0.6; 95% CI [0.6-0.9]); p < 0.001). Sacral end-plate thickness increased for male patients (p < 0.001) and was strongly correlated with height (r = 0.6; 95% CI [0.29-0.75]); p < 0.001) and weight (r = 0.8; 95% CI [0.6-0.9]); p < 0.001). The thickness of the inferior part of the S1 vertebral body increased in male patients (p < 0.001). Other measured parameters slightly varied according to gender, height and weight. Simulating the described technique of pelvic fixation, no misplaced IS screw was found whatever the age, gender and morphologic parameters. This user guide of spinopelvic fixation with IS screws seems to be reliable and reproducible independently of age, gender and morphologic characteristics but needs clinical assessment. Level IV.

A six-channel pediatric coil array for detection of children spinal pathologies by MRI at 1.5 Tesla

NASA Astrophysics Data System (ADS)

López Terrones, Marcos Alonso; Solís-Nájera, Sergio Enrique

2014-11-01

Nowadays, magnetic resonance (MR) in Mexico has become a standard technique for clinical imaging. Although most of the times the MR systems contain only coils oriented for adults. Radiologists use these coils for children studies due to the non-availability of pediatric coils. Image quality is decreased due to the low signal to noise ratio delivered to the system. The development of RF coils is always focused towards increasing SNR and optimizing the RF penetration into the sample. Moreover, spinal pathologies in children, which are an important topic in pediatric care, cover congenital and neuromuscular disorders that occur in childhood. In this work, the design of a dedicated six-channel coil for detection of spinal pathologies at 1.5 Tesla is addressed. Numerical electromagnetic simulations were performed in order to evaluate their magnetic field performance at (63.6 MHz) 1.5 Tesla. The magnetic field uniformity as well as the RF penetration depth of the coil configurations was evaluated in order to find the best/optimized coil array configuration. The coil is comprised of three rows, one with 4 coil elements and two with only one coil element. Phantom and in vivo images were acquired with the six-channel pediatric coil array. The phantom images agree with the simulated data. In vivo images acquired with the 6-channel pediatric coil array have shown very good penetration depth and homogeneity, which allow better image quality throughout the whole FOV. In addition, the parallel imaging capabilities of the array allow the acceleration of the experiments avoiding possible motion artifacts.

Vestibular lesion-induced developmental plasticity in spinal locomotor networks during Xenopus laevis metamorphosis.

PubMed

Beyeler, Anna; Rao, Guillaume; Ladepeche, Laurent; Jacques, André; Simmers, John; Le Ray, Didier

2013-01-01

During frog metamorphosis, the vestibular sensory system remains unchanged, while spinal motor networks undergo a massive restructuring associated with the transition from the larval to adult biomechanical system. We investigated in Xenopus laevis the impact of a pre- (tadpole stage) or post-metamorphosis (juvenile stage) unilateral labyrinthectomy (UL) on young adult swimming performance and underlying spinal locomotor circuitry. The acute disruptive effects on locomotion were similar in both tadpoles and juvenile frogs. However, animals that had metamorphosed with a preceding UL expressed restored swimming behavior at the juvenile stage, whereas animals lesioned after metamorphosis never recovered. Whilst kinematic and electrophysiological analyses of the propulsive system showed no significant differences in either juvenile group, a 3D biomechanical simulation suggested that an asymmetry in the dynamic control of posture during swimming could account for the behavioral restoration observed in animals that had been labyrinthectomized before metamorphosis. This hypothesis was subsequently supported by in vivo electromyography during free swimming and in vitro recordings from isolated brainstem/spinal cord preparations. Specifically, animals lesioned prior to metamorphosis at the larval stage exhibited an asymmetrical propulsion/posture coupling as a post-metamorphic young adult. This developmental alteration was accompanied by an ipsilesional decrease in propriospinal coordination that is normally established in strict left-right symmetry during metamorphosis in order to synchronize dorsal trunk muscle contractions with bilateral hindlimb extensions in the swimming adult. Our data thus suggest that a disequilibrium in descending vestibulospinal information during Xenopus metamorphosis leads to an altered assembly of adult spinal locomotor circuitry. This in turn enables an adaptive compensation for the dynamic postural asymmetry induced by the vestibular imbalance and the restoration of functionally-effective behavior.

Alpha-2 agonist attenuates ischemic injury in spinal cord neurons.

PubMed

Freeman, Kirsten A; Puskas, Ferenc; Bell, Marshall T; Mares, Joshua M; Foley, Lisa S; Weyant, Michael J; Cleveland, Joseph C; Fullerton, David A; Meng, Xianzhong; Herson, Paco S; Reece, T Brett

2015-05-01

Paraplegia secondary to spinal cord ischemia-reperfusion injury remains a devastating complication of thoracoabdominal aortic intervention. The complex interactions between injured neurons and activated leukocytes have limited the understanding of neuron-specific injury. We hypothesize that spinal cord neuron cell cultures subjected to oxygen-glucose deprivation (OGD) would simulate ischemia-reperfusion injury, which could be attenuated by specific alpha-2a agonism in an Akt-dependent fashion. Spinal cords from perinatal mice were harvested, and neurons cultured in vitro for 7-10 d. Cells were pretreated with 1 μM dexmedetomidine (Dex) and subjected to OGD in an anoxic chamber. Viability was determined by MTT assay. Deoxyuridine-triphosphate nick-end labeling staining and lactate dehydrogenase (LDH) assay were used for apoptosis and necrosis identification, respectively. Western blot was used for protein analysis. Vehicle control cells were only 59% viable after 1 h of OGD. Pretreatment with Dex significantly preserves neuronal viability with 88% viable (P < 0.05). Dex significantly decreased apoptotic cells compared with that of vehicle control cells by 50% (P < 0.05). Necrosis was not significantly different between treatment groups. Mechanistically, Dex treatment significantly increased phosphorylated Akt (P < 0.05), but protective effects of Dex were eliminated by an alpha-2a antagonist or Akt inhibitor (P < 0.05). Using a novel spinal cord neuron cell culture, OGD mimics neuronal metabolic derangement responsible for paraplegia after aortic surgery. Dex preserves neuronal viability and decreases apoptosis in an Akt-dependent fashion. Dex demonstrates clinical promise for reducing the risk of paraplegia after high-risk aortic surgery. Copyright © 2015 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitera, Gunita, E-mail: Gunita.Mitera@Sunnybrook.ca; Probyn, Linda; Ford, Michael

Purpose: To correlate computed tomography (CT) imaging features of spinal metastases with pain relief after radiotherapy (RT). Methods and Materials: Thirty-three patients receiving computed tomography (CT)-simulated RT for spinal metastases in an outpatient palliative RT clinic from January 2007 to October 2008 were retrospectively reviewed. Forty spinal metastases were evaluated. Pain response was rated using the International Bone Metastases Consensus Working Party endpoints. Three musculoskeletal radiologists and two orthopaedic surgeons evaluated CT features, including osseous and soft tissue tumor extent, presence of a pathologic fracture, severity of vertebral height loss, and presence of kyphosis. Results: The mean patient age wasmore » 69 years; 24 were men and 9 were women. The mean worst pain score was 7/10, and the mean total daily oral morphine equivalent was 77.3 mg. Treatment doses included 8 Gy in one fraction (22/33), 20 Gy in five fractions (10/33), and 20 Gy in eight fractions (1/33). The CT imaging appearance of spinal metastases included vertebral body involvement (40/40), pedicle involvement (23/40), and lamina involvement (18/40). Soft tissue component (10/40) and nerve root compression (9/40) were less common. Pathologic fractures existed in 11/40 lesions, with resultant vertebral body height loss in 10/40 and kyphosis in 2/40 lesions. At months 1, 2, and 3 after RT, 18%, 69%, and 70% of patients experienced pain relief. Pain response was observed with various CT imaging features. Conclusions: Pain response after RT did not differ in patients with and without pathologic fracture, kyphosis, or any other CT features related to extent of tumor involvement. All patients with painful spinal metastases may benefit from palliative RT.« less

Pathological lesions in the central nervous system and peripheral tissues of ddY mice with street rabies virus (1088 strain).

PubMed

Kimitsuki, Kazunori; Yamada, Kentaro; Shiwa, Nozomi; Inoue, Satoshi; Nishizono, Akira; Park, Chun-Ho

2017-06-10

Most studies on rabies virus pathogenesis in animal models have employed fixed rabies viruses, and the results of those employing street rabies viruses have been inconsistent. Therefore, to clarify the pathogenesis of street rabies virus (1088 strain) in mice, 10 6 focus forming units were inoculated into the right hindlimb of ddY mice (6 weeks, female). At 3 days postinoculation (DPI), mild inflammation was observed in the hindlimb muscle. At 5 DPI, ganglion cells in the right lumbosacral spinal dorsal root ganglia showed chromatolysis. Axonal degeneration and inflammatory cells increased with infection progress in the spinal dorsal horn and dorsal root ganglia. Right hindlimb paralysis was observed from 7 DPI, which progressed to quadriparalysis. However, no pathological changes were observed in the ventral horn and root fibers of the spinal cord. Viral antigen was first detected in the right hindlimb muscle at 3 DPI, followed by the right lumbosacral dorsal root ganglia, dorsal horn of spinal cord, left red nuclei, medulla oblongata and cerebral cortex (M1 area) at 5 DPI. These results suggested that the 1088 virus ascended the lumbosacral spinal cord via mainly afferent fibers at early stage of infection and moved to cerebral cortex (M1 area) using descending spinal tract. Additionally, we concluded that significant pathological changes in mice infected with 1088 strain occur in the sensory tract of the spinal cord; this selective susceptibility results in clinical features of the disease.

Progesterone Reduces Secondary Damage, Preserves White Matter, and Improves Locomotor Outcome after Spinal Cord Contusion

PubMed Central

Garcia-Ovejero, Daniel; González, Susana; Paniagua-Torija, Beatriz; Lima, Analía; Molina-Holgado, Eduardo; De Nicola, Alejandro F.

2014-01-01

Abstract Progesterone is an anti-inflammatory and promyelinating agent after spinal cord injury, but its effectiveness on functional recovery is still controversial. In the current study, we tested the effects of chronic progesterone administration on tissue preservation and functional recovery in a clinically relevant model of spinal cord lesion (thoracic contusion). Using magnetic resonance imaging, we observed that progesterone reduced both volume and rostrocaudal extension of the lesion at 60 days post-injury. In addition, progesterone increased the number of total mature oligodendrocytes, myelin basic protein immunoreactivity, and the number of axonal profiles at the epicenter of the lesion. Further, progesterone treatment significantly improved motor outcome as assessed using the Basso-Bresnahan-Beattie scale for locomotion and CatWalk gait analysis. These data suggest that progesterone could be considered a promising therapeutical candidate for spinal cord injury. PMID:24460450

Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury

PubMed Central

Keefe, Kathleen M.; Sheikh, Imran S.; Smith, George M.

2017-01-01

Neurotrophins are a family of proteins that regulate neuronal survival, synaptic function, and neurotransmitter release, and elicit the plasticity and growth of axons within the adult central and peripheral nervous system. Since the 1950s, these factors have been extensively studied in traumatic injury models. Here we review several members of the classical family of neurotrophins, the receptors they bind to, and their contribution to axonal regeneration and sprouting of sensory and motor pathways after spinal cord injury (SCI). We focus on nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and their effects on populations of neurons within diverse spinal tracts. Understanding the cellular targets of neurotrophins and the responsiveness of specific neuronal populations will allow for the most efficient treatment strategies in the injured spinal cord. PMID:28273811

Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury.

PubMed

Keefe, Kathleen M; Sheikh, Imran S; Smith, George M

2017-03-03

Neurotrophins are a family of proteins that regulate neuronal survival, synaptic function, and neurotransmitter release, and elicit the plasticity and growth of axons within the adult central and peripheral nervous system. Since the 1950s, these factors have been extensively studied in traumatic injury models. Here we review several members of the classical family of neurotrophins, the receptors they bind to, and their contribution to axonal regeneration and sprouting of sensory and motor pathways after spinal cord injury (SCI). We focus on nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and their effects on populations of neurons within diverse spinal tracts. Understanding the cellular targets of neurotrophins and the responsiveness of specific neuronal populations will allow for the most efficient treatment strategies in the injured spinal cord.

Orofacial inflammatory pain affects the expression of MT1 and NADPH-d in rat caudal spinal trigeminal nucleus and trigeminal ganglion

PubMed Central

Huang, Fang; He, Hongwen; Fan, Wenguo; Liu, Yongliang; Zhou, Hongyu; Cheng, Bin

2013-01-01

Very little is known about the role of melatonin in the trigeminal system, including the function of melatonin receptor 1. In the present study, adult rats were injected with formaldehyde into the right vibrissae pad to establish a model of orofacial inflammatory pain. The distribution of melatonin receptor 1 and nicotinamide adenine dinucleotide phosphate diaphorase in the caudal spinal trigeminal nucleus and trigeminal ganglion was determined with immunohistochemistry and histochemistry. The results show that there are significant differences in melatonin receptor 1 expression and nicotinamide adenine dinucleotide phosphate diaphorase expression in the trigeminal ganglia and caudal spinal nucleus during the early stage of orofacial inflammatory pain. Our findings suggest that when melatonin receptor 1 expression in the caudal spinal nucleus is significantly reduced, melatonin's regulatory effect on pain is attenuated. PMID:25206619

The modulatory role of alpha-melanocyte stimulating hormone administered spinally in the regulation of blood glucose level in d-glucose-fed and restraint stress mouse models.

PubMed

Sim, Yun-Beom; Park, Soo-Hyun; Kim, Sung-Su; Lim, Su-Min; Jung, Jun-Sub; Suh, Hong-Won

2014-08-01

Alpha-melanocyte stimulating hormone (α-MSH) is known as a regulator of the blood glucose homeostasis and food intake. In the present study, the possible roles of α-MSH located in the spinal cord in the regulation of the blood glucose level were investigated in d-glucose-fed and immobilization stress (IMO) mouse models. We found in the present study that intrathecal (i.t.) injection with α-MSH alone did not affect the blood glucose level. However, i.t. administration with α-MSH reduced the blood glucose level in d-glucose-fed model. The plasma insulin level was increased in d-glucose-fed model and was further increased by α-MSH, whereas α-MSH did not affect plasma corticosterone level in d-glucose-fed model. In addition, i.t. administration with glucagon alone enhanced blood glucose level and, i.t. injection with glucagon also increased the blood glucose level in d-glucose-fed model. In contrasted to results observed in d-glucose-fed model, i.t. treatment with α-MSH caused enhancement of the blood glucose level in IMO model. The plasma insulin level was increased in IMO model. The increased plasma insulin level by IMO was reduced by i.t. treatment with α-MSH, whereas i.t. pretreatment with α-MSH did not affect plasma corticosterone level in IMO model. Taken together, although spinally located α-MSH itself does not alter the blood glucose level, our results suggest that the activation of α-MSH system located in the spinal cord play important modulatory roles for the reduction of the blood glucose level in d-glucose fed model whereas α-MSH is responsible for the up-regulation of the blood glucose level in IMO model. The enhancement of insulin release may be responsible for modulatory action of α-MSH in down-regulation of the blood glucose in d-glucose fed model whereas reduction of insulin release may be responsible for modulatory action of α-MSH in up-regulation of the blood glucose in IMO model. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inflammatory response to Escherichia coli urinary tract infection in the neurogenic bladder of the spinal cord injured host.

PubMed

Chaudhry, Rajeev; Madden-Fuentes, Ramiro J; Ortiz, Tara K; Balsara, Zarine; Tang, Yuping; Nseyo, Unwanaobong; Wiener, John S; Ross, Sherry S; Seed, Patrick C

2014-05-01

Urinary tract infections cause significant morbidity in patients with spinal cord injury. An in vivo spinal cord injured rat model of experimental Escherichia coli urinary tract infection mimics human disease with enhanced susceptibility to urinary tract infection compared to controls. We hypothesized that a dysregulated inflammatory response contributes to enhanced susceptibility to urinary tract infection. Spinal cord injured and sham injured rats were inoculated transurethrally with E. coli. Transcript levels of 84 inflammatory pathway genes were measured in bladder tissue of each group before infection, 24 hours after infection and after 5 days of antibiotic therapy. Before infection quantitative polymerase chain reaction array revealed greater than twofold up-regulation in the proinflammatory factor transcripts slc11a1, ccl4 and il1β, and down-regulation of the antimicrobial peptides lcn2 and mpo in spinal cord injured vs control bladders. At 24 hours after infection spinal cord injured bladders showed an attenuated innate immune response with decreased expression of il6, slc11a1, il1β and lcn2, and decreased il10 and slpi expression compared to controls. Despite clearance of bacteriuria with antibiotics spinal cord injured rats had delayed induction of il6 transcription and a delayed anti-inflammatory response with decreased il10 and slpi transcript levels relative to controls. Spinal cord injured bladders fail to mount a characteristic inflammatory response to E. coli infection and cannot suppress inflammation after infection is eliminated. This may lead to increased susceptibility to urinary tract infection and persistent chronic inflammation through neural mediated pathways, which to our knowledge remain to be defined. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Content validity of manual spinal palpatory exams - A systematic review

PubMed Central

Najm, Wadie I; Seffinger, Michael A; Mishra, Shiraz I; Dickerson, Vivian M; Adams, Alan; Reinsch, Sibylle; Murphy, Linda S; Goodman, Arnold F

2003-01-01

Background Many health care professionals use spinal palpatory exams as a primary and well-accepted part of the evaluation of spinal pathology. However, few studies have explored the validity of spinal palpatory exams. To evaluate the status of the current scientific evidence, we conducted a systematic review to assess the content validity of spinal palpatory tests used to identify spinal neuro-musculoskeletal dysfunction. Methods Review of eleven databases and a hand search of peer-reviewed literature, published between 1965–2002, was undertaken. Two blinded reviewers abstracted pertinent data from the retrieved papers, using a specially developed quality-scoring instrument. Five papers met the inclusion/exclusion criteria. Results Three of the five papers included in the review explored the content validity of motion tests. Two of these papers focused on identifying the level of fixation (decreased mobility) and one focused on range of motion. All three studies used a mechanical model as a reference standard. Two of the five papers included in the review explored the validity of pain assessment using the visual analogue scale or the subjects' own report as reference standards. Overall the sensitivity of studies looking at range of motion tests and pain varied greatly. Poor sensitivity was reported for range of motion studies regardless of the examiner's experience. A slightly better sensitivity (82%) was reported in one study that examined cervical pain. Conclusions The lack of acceptable reference standards may have contributed to the weak sensitivity findings. Given the importance of spinal palpatory tests as part of the spinal evaluation and treatment plan, effort is required by all involved disciplines to create well-designed and implemented studies in this area. PMID:12734016

Effects of electroacupuncture and the retinoid X receptor (RXR) signalling pathway on oligodendrocyte differentiation in the demyelinated spinal cord of rats

PubMed Central

Yang, Xiao-Hua; Ding, Ying; Li, Wen; Zhang, Rong-Yi; Wu, Jin-Lang; Ling, Eng-Ang; Wu, Wutian

2017-01-01

Objectives In spinal cord demyelination, some oligodendrocyte precursor cells (OPCs) remain in the demyelinated region but have a reduced capacity to differentiate into oligodendrocytes. This study investigated whether ‘Governor Vessel’ (GV) electroacupuncture (EA) would promote the differentiation of endogenous OPCs into oligodendrocytes by activating the retinoid X receptor γ (RXR-γ)-mediated signalling pathway. Methods Adult rats were microinjected with ethidium bromide (EB) into the T10 spinal cord to establish a model of spinal cord demyelination. EB-injected rats remained untreated (EB group, n=26) or received EA treatment (EB+EA group, n=26). A control group (n=26) was also included that underwent dural exposure without EB injection. After euthanasia at 7 days (n=5 per group), 15 days (n=8 per group) or 30 days (n=13 per group), protein expression of RXR-γ in the demyelinated spinal cord was evaluated by immunohistochemistry and Western blotting. In addition, OPCs derived from rat embryonic spinal cord were cultured in vitro, and exogenous 9-cis-RA (retinoic acid) and RXR-γ antagonist HX531 were administered to determine whether RA could activate RXR-γ and promote OPC differentiation. Results EA was found to increase the numbers of both OPCs and oligodendrocytes expressing RXR-γ and RALDH2, and promote remyelination in the remyelinated spinal cord. Exogenous 9-cis-RA enhanced the differentiation of OPCs into mature oligodendrocytes by activating RXR-γ. Conclusions The results suggest that EA may activate RXR signalling to promote the differentiation of OPCs into oligodendrocytes in spinal cord demyelination. PMID:27841975

Agar-based bridges as biocompatible candidates to provide guide cues in spinal cord injury repair.

PubMed

Martín-López, Eduardo; Darder, Margarita; Ruiz-Hitzky, Eduardo; Nieto Sampedro, Manuel

2013-01-01

Spinal bridge implants are strategic to provide growth surfaces for axonal regeneration after spinal cord injuries. The design of an appropriate substrate, one that is suitable for implantation, must involve careful testing of the biomaterial properties both in vitro and in vivo. The goal of this work was to test the structure, stability and biological response after spinal bridges implantation of several biopolymers, composed of mixtures of agar (AG), as structural matrix scaffold, with κ-carrageenan (Kc), gelatin (G), xanthan gum (Xn) and polysulfone (PS). Biopolymer structures were studied by environmental scanning electron microscopy, whereas the stability of gels was analyzed by in vitro degradation and swelling tests. The biocompatibility of these materials and their ability to promote cell growth and axonal regeneration were studied by implantation of spinal bridges containing empty linear channels in an acute rat spinal cord transection model at thoracic level (T8). All gel mixtures gave rise to porous structures and they were stables to degradation, excepting the AG+G mixture. Spinal bridges constructed from all mixtures were implanted during a month in adult rats. After this time a low host reaction occurred to all bridge materials as well as neurite and cell ingrowths through the empty channels. Neurites within the bridges were mostly peripheral sensory fibers such as those positive for CGRP, whereas there was a lack of regeneration of central axons crossing from the spinal tissue to bridges. Many of these neurites established closed contacts with non-myelin Schwann cells. The histological analysis revealed a high accumulation of collagen fibers within the channels. Unexpected was the apparent loss of channels linearity which affected the growth of neurites and cells, indicating the need for additional regeneration strategies and vertebrae bridge fixing.

Spinal cord repair in MS

PubMed Central

Ciccarelli, O.; Altmann, D. R.; McLean, M. A.; Wheeler-Kingshott, C. A.; Wimpey, K.; Miller, D. H.; Thompson, A. J.

2010-01-01

Objective: To investigate the mechanisms of spinal cord repair and their relative contribution to clinical recovery in patients with multiple sclerosis (MS) after a cervical cord relapse, using spinal cord 1H-magnetic resonance spectroscopy (MRS) and volumetric imaging. Methods: Fourteen patients with MS and 13 controls underwent spinal cord imaging at baseline and at 1, 3, and 6 months. N-acetyl-aspartate (NAA) concentration, which reflects axonal count and metabolism in mitochondria, and the cord cross-sectional area, which indicates axonal count, were measured in the affected cervical region. Mixed effect linear regression models investigated the temporal evolution of these measures and their association with clinical changes. Ordinal logistic regressions identified predictors of recovery. Results: Patients who recovered showed a sustained increase in NAA after 1 month. In the whole patient group, a greater increase of NAA after 1 month was associated with greater recovery. Patients showed a significant decline in cord area during follow-up, which did not correlate with clinical changes. A worse recovery was predicted by a longer disease duration at study entry. Conclusions: The partial recovery of N-acetyl-aspartate levels after the acute event, which is concurrent with a decline in cord cross-sectional area, may be driven by increased axonal mitochondrial metabolism. This possible repair mechanism is associated with clinical recovery, and is less efficient in patients with longer disease duration. These insights into the mechanisms of spinal cord repair highlight the need to extend spinal cord magnetic resonance spectroscopy to other spinal cord disorders, and explore therapies that enhance recovery by modulating mitochondrial activity. GLOSSARY CI = confidence interval; EDSS = Expanded Disability Status Scale; FOV = field of view; MR = magnetic resonance; MRS = magnetic resonance spectroscopy; MS = multiple sclerosis; NAA = N-acetyl-aspartate; SC = spinal cord; TE = echo time; TI = inversion time; TR = repetition time. PMID:20107138

Comparison of Diffusion MRI Acquisition Protocols for the In Vivo Characterization of the Mouse Spinal Cord: Variability Analysis and Application to an Amyotrophic Lateral Sclerosis Model

PubMed Central

Marcuzzo, Stefania; Bonanno, Silvia; Padelli, Francesco; Moreno-Manzano, Victoria; García-Verdugo, José Manuel; Bernasconi, Pia; Mantegazza, Renato; Bruzzone, Maria Grazia; Zucca, Ileana

2016-01-01

Diffusion-weighted Magnetic Resonance Imaging (dMRI) has relevant applications in the microstructural characterization of the spinal cord, especially in neurodegenerative diseases. Animal models have a pivotal role in the study of such diseases; however, in vivo spinal dMRI of small animals entails additional challenges that require a systematical investigation of acquisition parameters. The purpose of this study is to compare three acquisition protocols and identify the scanning parameters allowing a robust estimation of the main diffusion quantities and a good sensitivity to neurodegeneration in the mouse spinal cord. For all the protocols, the signal-to-noise and contrast-to noise ratios and the mean value and variability of Diffusion Tensor metrics were evaluated in healthy controls. For the estimation of fractional anisotropy less variability was provided by protocols with more diffusion directions, for the estimation of mean, axial and radial diffusivity by protocols with fewer diffusion directions and higher diffusion weighting. Intermediate features (12 directions, b = 1200 s/mm2) provided the overall minimum inter- and intra-subject variability in most cases. In order to test the diagnostic sensitivity of the protocols, 7 G93A-SOD1 mice (model of amyotrophic lateral sclerosis) at 10 and 17 weeks of age were scanned and the derived diffusion parameters compared with those estimated in age-matched healthy animals. The protocols with an intermediate or high number of diffusion directions provided the best differentiation between the two groups at week 17, whereas only few local significant differences were highlighted at week 10. According to our results, a dMRI protocol with an intermediate number of diffusion gradient directions and a relatively high diffusion weighting is optimal for spinal cord imaging. Further work is needed to confirm these results and for a finer tuning of acquisition parameters. Nevertheless, our findings could be important for the optimization of acquisition protocols for preclinical and clinical dMRI studies on the spinal cord. PMID:27560686