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.

The change tendency of PI3K/Akt pathway after spinal cord injury

PubMed Central

Zhang, Peixun; Zhang, Luping; Zhu, Lei; Chen, Fangmin; Zhou, Shuai; Tian, Ting; Zhang, Yuqiang; Jiang, Xiaorui; Li, Xuekun; Zhang, Chuansen; Xu, Lin; Huang, Fei

2015-01-01

Spinal cord injury (SCI) refers to the damage of spinal cord’s structure and function due to a variety of causes. At present, many scholars have confirmed that apoptosis is the main method of secondary injury in spinal cord injury. In view of understanding the function of PI3K/Akt pathway on spinal cord injury, this study observed the temporal variation of key molecules (PI3K, Akt, p-Akt) in the PI3K/Akt pathway after spinal cord injury by immunohistochemistry and Western-blot. The results showed that the expression of PI3K, Akt and p-Akt display a sharp increase one day after the spinal cord injury, and then it decreased gradually with the time passing by, but the absolute expression was certainly higher than the normal group. These results indicate that the PI3K/Akt signaling pathway is involved in the spinal cord injury and the mechanism may be related to apoptosis. PMID:26807170

Multiple sclerosis lesions affect intrinsic functional connectivity of the spinal cord.

PubMed

Conrad, Benjamin N; Barry, Robert L; Rogers, Baxter P; Maki, Satoshi; Mishra, Arabinda; Thukral, Saakshi; Sriram, Subramaniam; Bhatia, Aashim; Pawate, Siddharama; Gore, John C; Smith, Seth A

2018-06-01

Patients with multiple sclerosis present with focal lesions throughout the spinal cord. There is a clinical need for non-invasive measurements of spinal cord activity and functional organization in multiple sclerosis, given the cord's critical role in the disease. Recent reports of spontaneous blood oxygenation level-dependent fluctuations in the spinal cord using functional MRI suggest that, like the brain, cord activity at rest is organized into distinct, synchronized functional networks among grey matter regions, likely related to motor and sensory systems. Previous studies looking at stimulus-evoked activity in the spinal cord of patients with multiple sclerosis have demonstrated increased levels of activation as well as a more bilateral distribution of activity compared to controls. Functional connectivity studies of brain networks in multiple sclerosis have revealed widespread alterations, which may take on a dynamic trajectory over the course of the disease, with compensatory increases in connectivity followed by decreases associated with structural damage. We build upon this literature by examining functional connectivity in the spinal cord of patients with multiple sclerosis. Using ultra-high field 7 T imaging along with processing strategies for robust spinal cord functional MRI and lesion identification, the present study assessed functional connectivity within cervical cord grey matter of patients with relapsing-remitting multiple sclerosis (n = 22) compared to a large sample of healthy controls (n = 56). Patient anatomical images were rated for lesions by three independent raters, with consensus ratings revealing 19 of 22 patients presented with lesions somewhere in the imaged volume. Linear mixed models were used to assess effects of lesion location on functional connectivity. Analysis in control subjects demonstrated a robust pattern of connectivity among ventral grey matter regions as well as a distinct network among dorsal regions. A gender effect was also observed in controls whereby females demonstrated higher ventral network connectivity. Wilcoxon rank-sum tests detected no differences in average connectivity or power of low frequency fluctuations in patients compared to controls. The presence of lesions was, however, associated with local alterations in connectivity with differential effects depending on columnar location. The patient results suggest that spinal cord functional networks are generally intact in relapsing-remitting multiple sclerosis but that lesions are associated with focal abnormalities in intrinsic connectivity. These findings are discussed in light of the current literature on spinal cord functional MRI and the potential neurological underpinnings.

Changes in Afferent Activity After Spinal Cord Injury

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2010-01-01

Aims To summarize the changes that occur in the properties of bladder afferent neurons following spinal cord injury. Methods Literature review of anatomical, immunohistochemical, and pharmacologic studies of normal and dysfunctional bladder afferent pathways. Results Studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through coordination centers (periaqueductal gray and pontine micturition center) located in the rostral brain stem. This reflex pathway, which is activated by small myelinated (Aδ) bladder afferent nerves, is in turn modulated by higher centers in the cerebral cortex involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary voiding, as well as the normal reflex pathways that coordinate bladder and sphincter function. Following spinal cord injury, the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. The recovery of bladder function after spinal cord injury is dependent in part on the plasticity of bladder afferent pathways and the unmasking of reflexes triggered by unmyelinated, capsaicin-sensitive, C-fiber bladder afferent neurons. Plasticity is associated with morphologic, chemical, and electrical changes in bladder afferent neurons and appears to be mediated in part by neurotrophic factors released in the spinal cord and the peripheral target organs. Conclusions Spinal cord injury at sites remote from the lumbosacral spinal cord can indirectly influence properties of bladder afferent neurons by altering the function and chemical environment in the bladder or the spinal cord. PMID:20025033

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

Functional MR imaging of the cervical spinal cord by use of electrical stimulation at LI4 (Hegu).

PubMed

Wang, W D; Kong, K M; Xiao, Y Y; Wang, X J; Liang, B; Qi, W L; Wu, R H

2006-01-01

The purpose is to investigate the cervical spinal cord mapping on electrical stimulation at LI4 (Hegu) by using 'signal enhancement by extravascular water protons' (SEEP)-fMRI, and to establish the response of acupoint-stimulation in spinal cord. Three healthy volunteers were underwent low-frequency electrical stimulation at LI4. Meanwhile, a single-shot fast spin-echo (SSFSE) sequence was used to perform functional MR imaging on a 1.5 T GE Signa MR system. Cord activation was measured both in the sagittal and transverse imaging planes and then analyzed by AFNI (analysis of functional neuroimages) system. In the sagittal view, two subjects had an fMRI response in the cervical spinal cord upon electrical stimulation at LI4. The localizations of the segmental fMRI activation are both at C6 through T1 and C2/3 cervical spinal cord level. In the transverse imaging plane, significant fMRI responses could be measured in the last subjects locating at C6/7 segment, the cross-sectional localization of the activity measured in the spinal cord was most in terms of the ipsilateral posterior direction. It is concluded that the fMRI technique can be used for detecting with activity in the human cervical spinal cord by a single-shot fast spin-echo sequence on a 1.5 T GE clinical system. Investigating the acupoint-stimulation response in the spinal cord using the spinal fMRI will be helpful for the further discussion on the mechanisms of acupuncture to spinal cord diseases.

Update on traumatic acute spinal cord injury. Part 2.

PubMed

Mourelo Fariña, M; Salvador de la Barrera, S; Montoto Marqués, A; Ferreiro Velasco, M E; Galeiras Vázquez, R

The aim of treatment in acute traumatic spinal cord injury is to preserve residual neurologic function, avoid secondary injury, and restore spinal alignment and stability. In this second part of the review, we describe the management of spinal cord injury focusing on issues related to short-term respiratory management, where the preservation of diaphragmatic function is a priority, with prediction of the duration of mechanical ventilation and the need for tracheostomy. Surgical assessment of spinal injuries based on updated criteria is discussed, taking into account that although the type of intervention depends on the surgical team, nowadays treatment should afford early spinal decompression and stabilization. Within a comprehensive strategy in spinal cord injury, it is essential to identify and properly treat patient anxiety and pain associated to spinal cord injury, as well as to prevent and ensure the early diagnosis of complications secondary to spinal cord injury (thromboembolic disease, gastrointestinal and urinary disorders, pressure ulcers). Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

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

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.

Management of chronic spinal cord dysfunction.

PubMed

Abrams, Gary M; Ganguly, Karunesh

2015-02-01

Both acute and chronic spinal cord disorders present multisystem management problems to the clinician. This article highlights key issues associated with chronic spinal cord dysfunction. Advances in symptomatic management for chronic spinal cord dysfunction include use of botulinum toxin to manage detrusor hyperreflexia, pregabalin for management of neuropathic pain, and intensive locomotor training for improved walking ability in incomplete spinal cord injuries. The care of spinal cord dysfunction has advanced significantly over the past 2 decades. Management and treatment of neurologic and non-neurologic complications of chronic myelopathies ensure that each patient will be able to maximize their functional independence and quality of life.

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.

The triple monoamine re-uptake inhibitor DOV 216,303 promotes functional recovery after spinal cord contusion injury in mice.

PubMed

Chu, Tak-Ho; Cummins, Karen; Stys, Peter K

2018-05-14

Serotonin, noradrenaline and dopamine are important neuromodulators for locomotion in the spinal cord. Disruption of descending axons after spinal cord injury resulted in reduction of excitatory and neuromodulatory inputs to spinal neurons for locomotion. Receptor agonists or reuptake inhibitors for these neuromodulators have been shown to be beneficial in incomplete spinal cord injury. In this study, we tested a triple re-uptake inhibitor, DOV 216,303, for its ability to affect motor function recovery after spinal cord injury in mice. We impacted C57 mouse spinal cord at the T11 vertebral level and administered vehicle or DOV 216,303 at 10 mg/kg, b.i.d via intraperitoneal injections for 7 days. We monitored motor function with the Basso Mouse Scale for locomotion for 4 weeks. Spinal cords were harvested and histological examinations were performed to assess tissue sparing and lesion severity. Results showed that DOV 216,303-treated mice recovered significantly better than vehicle treated mice starting at 14 days post injury until the end of the survival period. Lesion size of the DOV 216,303 treated mice was also smaller compared to that of vehicle treated mice. This study suggests DOV 216,303 as a potential therapeutic after spinal cord injury warrants further investigation. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Locomotor recovery after spinal cord hemisection/contusion injures in bonnet monkeys: footprint testing--a minireview.

PubMed

Rangasamy, Suresh Babu

2013-07-01

Spinal cord injuries usually produce loss or impairment of sensory, motor and reflex function below the level of damage. In the absence of functional regeneration or manipulations that promote regeneration, spontaneous improvements in motor functions occur due to the activation of multiple compensatory mechanisms in animals and humans following the partial spinal cord injury. Many studies were performed on quantitative evaluation of locomotor recovery after induced spinal cord injury in animals using behavioral tests and scoring techniques. Although few studies on rodents have led to clinical trials, it would appear imperative to use nonhuman primates such as macaque monkeys in order to relate the research outcomes to recovery of functions in humans. In this review, we will discuss some of our research evidences concerning the degree of spontaneous recovery in bipedal locomotor functions of bonnet monkeys that underwent spinal cord hemisection/contusion lesions. To our knowledge, this is the first report to discuss on the extent of spontaneous recovery in bipedal locomotion of macaque monkeys through the application of footprint analyzing technique. In addition, the results obtained were compared with the published data on recovery of quadrupedal locomotion of spinally injured rodents. We propose that the mechanisms underlying spontaneous recovery of functions in spinal cord lesioned monkeys may be correlated to the mature function of spinal pattern generator for locomotion under the impact of residual descending and afferent connections. Moreover, based on analysis of motor functions observed in locomotion in these subjected monkeys, we understand that spinal automatism and development of responses by afferent stimuli from outside the cord could possibly contribute to recovery of paralyzed hindlimbs. This report also emphasizes the functional contribution of progressive strengthening of undamaged nerve fibers through a collateral sprouts/synaptic plasticity formed in partially lesioned cord of monkeys. Copyright © 2013 Wiley Periodicals, Inc.

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.

Recovery of neuronal and network excitability after spinal cord injury and implications for spasticity

PubMed Central

D'Amico, Jessica M.; Condliffe, Elizabeth G.; Martins, Karen J. B.; Bennett, David J.; Gorassini, Monica A.

2014-01-01

The state of areflexia and muscle weakness that immediately follows a spinal cord injury (SCI) is gradually replaced by the recovery of neuronal and network excitability, leading to both improvements in residual motor function and the development of spasticity. In this review we summarize recent animal and human studies that describe how motoneurons and their activation by sensory pathways become hyperexcitable to compensate for the reduction of functional activation of the spinal cord and the eventual impact on the muscle. Specifically, decreases in the inhibitory control of sensory transmission and increases in intrinsic motoneuron excitability are described. We present the idea that replacing lost patterned activation of the spinal cord by activating synaptic inputs via assisted movements, pharmacology or electrical stimulation may help to recover lost spinal inhibition. This may lead to a reduction of uncontrolled activation of the spinal cord and thus, improve its controlled activation by synaptic inputs to ultimately normalize circuit function. Increasing the excitation of the spinal cord with spared descending and/or peripheral inputs by facilitating movement, instead of suppressing it pharmacologically, may provide the best avenue to improve residual motor function and manage spasticity after SCI. PMID:24860447

Functional MR imaging of the spinal cord in cervical spinal cord injury patients by acupuncture at LI 4 (Hegu) and LI 11(Quchi).

PubMed

Chen, Y X; Kong, K M; Wang, W D; Xie, C H; Wu, R H

2007-01-01

To investigate the cervical spinal cord mapping on acupuncture at LI 4 (Hegu) and LI 11 (Quchi) by using 'Signal Enhancement by Extravascular water Protons' (SEEP)-fMRI, and to establish the response of using acupuncture in the cervical spinal cord. This research may provide some laboratory evidences from the acupuncture treatment on the cervical spinal cord of injuried patients. Seven healthy volunteers (healthy group) and three cervical spinal cord injury patients (injury group) were underwent low-frequency electrical stimulation at LI 4 and LI 11. Meanwhile, a single-shot fast spin-echo (SSFSE) sequence was used to perform functional MR imaging on a 1.5 T GE Signa MR system. The signals from the cervical spinal cord activated was measured both in sagittal and transverse imaging planes and then analyzed by AFNI (Analysis of Functional Neuroimages) system. It was found that in the sagittal view, two groups had an fMRI response in the cervical spinal cord after given acupuncture treatments at LI 4 and LI 11. The localizations of the segmental fMRI activation were focused at C6 and C2 cervical spinal cord level. In the transverse imaging plane, significant fMRI responses could be measured from the four of seven healthy volunteers and from two of three cervical spinal cord injury patients. They were located at C6/7 segments. The cross-sectional localization of the activity measured in the spinal cord was most in terms of the ipsilateral posterior direction. The signal amplitude varied mainly between 6.8%17.8%. However, the difference found between the two groups had no statistical meaning. The fMRI technique had detected an activation focused at C6 and C2 cervical spinal cord levels by use of acupuncture at LI 4 and LI 11 on a 1.5T GE clinical system. This proved that the meridians and points are found to be in existence. The fMRI can be used as a harmless research method to discuss the mechanisms of acupuncture as well as study the mechanisms of spinal cord diseases. It can be used to direct or monitor the related therapy on the spinal cord injury patients.

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

Tissue-Engineered Regeneration of Hemisected Spinal Cord Using Human Endometrial Stem Cells, Poly ε-Caprolactone Scaffolds, and Crocin as a Neuroprotective Agent.

PubMed

Terraf, Panieh; Kouhsari, Shideh Montasser; Ai, Jafar; Babaloo, Hamideh

2017-09-01

Loss of motor and sensory function as a result of neuronal cell death and axonal degeneration are the hallmarks of spinal cord injury. To overcome the hurdles and achieve improved functional recovery multiple aspects, it must be taken into account. Tissue engineering approaches by coalescing biomaterials and stem cells offer a promising future for treating spinal cord injury. Here we investigated human endometrial stem cells (hEnSCs) as our cell source. Electrospun poly ε-caprolactone (PCL) scaffolds were used for hEnSC adhesion and growth. Scanning electron microscopy (SEM) confirmed the attachment and survival of stem cells on the PCL scaffolds. The scaffold-stem cell construct was transplanted into the hemisected spinal cords of adult male rats. Crocin, an ethanol-extractable component of Crocus sativus L., was administered to rats for 15 consecutive days post injury. Neurite outgrowth and axonal regeneration were investigated using immunohistochemical staining for neurofilament marker NF-H and luxol-fast blue (LFB) staining, respectively. TNF-α staining was performed to determine the inflammatory response in each group. Functional recovery was assessed via the Basso-Beattie-Bresnahan (BBB) scale. Results showed that PCL scaffolds seeded with hEnSCs restored the continuity of the damaged spinal cord and decreased cavity formation. Additionally, hEnSC-seeded scaffolds contributed to the functional recovery of the spinal cord. Hence, hEnSC-seeded PCL scaffolds may serve as promising transplants for spinal cord tissue engineering purposes. Furthermore, crocin had an augmenting effect on spinal cord regeneration and proved to exert neuroprotective effects on damaged neurons and may be further studied as a promising drug for spinal cord injury.

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.

Sexuality and sexual dysfunction in spinal cord-injured men in Turkey.

PubMed

Akman, Ramazan Yavuz; Coşkun Çelik, Evrim; Karataş, Metin

2015-01-01

To provide a comprehensive evaluation of sexual function and dysfunction in spinal cord-injured men based on self-reports of patients. Forty-seven spinal cord-injured men who completed the spinal shock and rehabilitation period were included. Patients were asked to complete a questionnaire developed to assess social status, sexual activities, abilities, and sexuality education after injury. Neurologic levels of patients were classified according to American Spinal Cord Injury Association protocol. Erectile function was evaluated by International Index of Erectile Function-5 (IIEF-5) questionnaire. Patients were aged between 20 and 62 years (mean: 35.2). Twenty-eight patients had T10 and above, 15 between T11 and L2, and 4 cauda conus injury. While 61.7% of the patients declared sexual activity, 93.6% declared some degree of erection. Mean IIEF-5 score was 5.3 and 87.3% of the patients had moderate to severe erectile dysfunction. Continuation of sexual activity after injury is very important and has a great impact on quality of life and interpersonal relationships for spinal cord-injured men. More attention must be given to sexuality after spinal cord injury. A very high rate of sexual dysfunction in spinal cord-injured patients was found and the importance of sexual education was emphasized in this study.

Neuromodulation of lower limb motor control in restorative neurology.

PubMed

Minassian, Karen; Hofstoetter, Ursula; Tansey, Keith; Mayr, Winfried

2012-06-01

One consequence of central nervous system injury or disease is the impairment of neural control of movement, resulting in spasticity and paralysis. To enhance recovery, restorative neurology procedures modify altered, yet preserved nervous system function. This review focuses on functional electrical stimulation (FES) and spinal cord stimulation (SCS) that utilize remaining capabilities of the distal apparatus of spinal cord, peripheral nerves and muscles in upper motor neuron dysfunctions. FES for the immediate generation of lower limb movement along with current rehabilitative techniques is reviewed. The potential of SCS for controlling spinal spasticity and enhancing lower limb function in multiple sclerosis and spinal cord injury is discussed. The necessity for precise electrode placement and appropriate stimulation parameter settings to achieve therapeutic specificity is elaborated. This will lead to our human work of epidural and transcutaneous stimulation targeting the lumbar spinal cord for enhancing motor functions in spinal cord injured people, supplemented by pertinent human research of other investigators. We conclude that the concept of restorative neurology recently received new appreciation by accumulated evidence for locomotor circuits residing in the human spinal cord. Technological and clinical advancements need to follow for a major impact on the functional recovery in individuals with severe damage to their motor system. Copyright © 2012 Elsevier B.V. All rights reserved.

Neuromodulation of lower limb motor control in restorative neurology

PubMed Central

Minassian, Karen; Hofstoetter, Ursula; Tansey, Keith; Mayr, Winfried

2012-01-01

One consequence of central nervous system injury or disease is the impairment of neural control of movement, resulting in spasticity and paralysis. To enhance recovery, restorative neurology procedures modify altered, yet preserved nervous system function. This review focuses on functional electrical stimulation (FES) and spinal cord stimulation (SCS) that utilize remaining capabilities of the distal apparatus of spinal cord, peripheral nerves and muscles in upper motor neuron dysfunctions. FES for the immediate generation of lower limb movement along with current rehabilitative techniques is reviewed. The potential of SCS for controlling spinal spasticity and enhancing lower limb function in multiple sclerosis and spinal cord injury is discussed. The necessity for precise electrode placement and appropriate stimulation parameter settings to achieve therapeutic specificity is elaborated. This will lead to our human work of epidural and transcutaneous stimulation targeting the lumbar spinal cord for enhancing motor functions in spinal cord injured people, supplemented by pertinent human research of other investigators. We conclude that the concept of restorative neurology recently received new appreciation by accumulated evidence for locomotor circuits residing in the human spinal cord. Technological and clinical advancements need to follow for a major impact on the functional recovery in individuals with severe damage to their motor system. PMID:22464657

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.

Fractionated radiation facilitates repair and functional motor recovery after spinal cord transection in rat.

PubMed

Kalderon, N; Xu, S; Koutcher, J A; Fuks, Z

2001-06-22

Previous studies suggest that motor recovery does not occur after spinal cord injury because reactive glia abort the natural repair processes. A permanent wound gap is left in the cord and the brain-cord circuitry consequently remains broken. Single-dose x-irradiation destroys reactive glia at the damage site in transected adult rat spinal cord. The wound then heals naturally, and a partially functional brain-cord circuitry is reconstructed. Timing is crucial; cell ablation is beneficial only within the third week after injury. Data presented here point to the possibility of translating these observations into a clinical therapy for preventing the paralysis following spinal cord injury in the human. The lesion site (at low thoracic level) in severed adult rat spinal cord was treated daily, over the third week postinjury, with protocols of fractionated radiation similar to those for treating human spinal cord tumors. This resulted, as with the single-dose protocol, in wound healing and restoration of some hindquarter motor function; in addition, the beneficial outcome was augmented. Of the restored hindlimb motor functions, weight-support and posture in stance was the only obvious one. Recovery of this motor function was partial to substantial and its incidence was 100% instead of about 50% obtained with the single-dose treatment. None of the hindlimbs, however, regained frequent stepping or any weight-bearing locomotion. These data indicate that the therapeutic outcome may be further augmented by tuning the radiation parameters within the critical time-window after injury. These data also indicate that dose-fractionation is an effective strategy and better than the single-dose treatment for targeting of reactive cells that abort the natural repair, suggesting that radiation therapy could be developed into a therapeutic procedure for repairing injured spinal cord.

The spinal cord: a review of functional neuroanatomy.

PubMed

Bican, Orhan; Minagar, Alireza; Pruitt, Amy A

2013-02-01

The spinal cord controls the voluntary muscles of the trunk and limbs and receives sensory input from these areas. It extends from the medulla oblongata to the lower border of the first lumbar vertebra. A basic knowledge of spinal cord anatomy is essential for interpretation of clinical signs and symptoms and for understanding of pathologic processes involving the spinal cord. In this article, anatomic structures are correlated with relevant clinical signs and symptoms and a step-wise approach to spinal cord diagnosis is outlined. Copyright © 2013 Elsevier Inc. All rights reserved.

Transcranial cerebellar direct current stimulation and transcutaneous spinal cord direct current stimulation as innovative tools for neuroscientists

PubMed Central

Priori, Alberto; Ciocca, Matteo; Parazzini, Marta; Vergari, Maurizio; Ferrucci, Roberta

2014-01-01

Two neuromodulatory techniques based on applying direct current (DC) non-invasively through the skin, transcranial cerebellar direct current stimulation (tDCS) and transcutaneous spinal DCS, can induce prolonged functional changes consistent with a direct influence on the human cerebellum and spinal cord. In this article we review the major experimental works on cerebellar tDCS and on spinal tDCS, and their preliminary clinical applications. Cerebellar tDCS modulates cerebellar motor cortical inhibition, gait adaptation, motor behaviour, and cognition (learning, language, memory, attention). Spinal tDCS influences the ascending and descending spinal pathways, and spinal reflex excitability. In the anaesthetised mouse, DC stimulation applied under the skin along the entire spinal cord may affect GABAergic and glutamatergic systems. Preliminary clinical studies in patients with cerebellar disorders, and in animals and patients with spinal cord injuries, have reported beneficial effects. Overall the available data show that cerebellar tDCS and spinal tDCS are two novel approaches for inducing prolonged functional changes and neuroplasticity in the human cerebellum and spinal cord, and both are new tools for experimental and clinical neuroscientists. PMID:24907311

[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.

Zebrafish transgenic constructs label specific neurons in Xenopus laevis spinal cord and identify frog V0v spinal neurons.

PubMed

Juárez-Morales, José L; Martinez-De Luna, Reyna I; Zuber, Michael E; Roberts, Alan; Lewis, Katharine E

2017-09-01

A correctly functioning spinal cord is crucial for locomotion and communication between body and brain but there are fundamental gaps in our knowledge of how spinal neuronal circuitry is established and functions. To understand the genetic program that regulates specification and functions of this circuitry, we need to connect neuronal molecular phenotypes with physiological analyses. Studies using Xenopus laevis tadpoles have increased our understanding of spinal cord neuronal physiology and function, particularly in locomotor circuitry. However, the X. laevis tetraploid genome and long generation time make it difficult to investigate how neurons are specified. The opacity of X. laevis embryos also makes it hard to connect functional classes of neurons and the genes that they express. We demonstrate here that Tol2 transgenic constructs using zebrafish enhancers that drive expression in specific zebrafish spinal neurons label equivalent neurons in X. laevis and that the incorporation of a Gal4:UAS amplification cassette enables cells to be observed in live X. laevis tadpoles. This technique should enable the molecular phenotypes, morphologies and physiologies of distinct X. laevis spinal neurons to be examined together in vivo. We have used an islet1 enhancer to label Rohon-Beard sensory neurons and evx enhancers to identify V0v neurons, for the first time, in X. laevis spinal cord. Our work demonstrates the homology of spinal cord circuitry in zebrafish and X. laevis, suggesting that future work could combine their relative strengths to elucidate a more complete picture of how vertebrate spinal cord neurons are specified, and function to generate behavior. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1007-1020, 2017. © 2017 Wiley Periodicals, Inc.

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.

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.

Comparing patients with spinal cord infarction and cerebral infarction: clinical characteristics, and short-term outcome.

PubMed

Naess, Halvor; Romi, Fredrik

2011-01-01

To compare the clinical characteristics, and short-term outcome of spinal cord infarction and cerebral infarction. Risk factors, concomitant diseases, neurological deficits on admission, and short-term outcome were registered among 28 patients with spinal cord infarction and 1075 patients with cerebral infarction admitted to the Department of Neurology, Haukeland University Hospital, Bergen, Norway. Multivariate analyses were performed with location of stroke (cord or brain), neurological deficits on admission, and short-term outcome (both Barthel Index [BI] 1 week after symptom onset and discharge home or to other institution) as dependent variables. Multivariate analysis showed that patients with spinal cord infarction were younger, more often female, and less afflicted by hypertension and cardiac disease than patients with cerebral infarction. Functional score (BI) was lower among patients with spinal cord infarctions 1 week after onset of symptoms (P < 0.001). Odds ratio for being discharged home was 5.5 for patients with spinal cord infarction compared to cerebral infarction after adjusting for BI scored 1 week after onset (P = 0.019). Patients with spinal cord infarction have a risk factor profile that differs significantly from that of patients with cerebral infarction, although there are some parallels to cerebral infarction caused by atherosclerosis. Patients with spinal cord infarction were more likely to be discharged home when adjusting for early functional level on multivariate analysis.

Comparing patients with spinal cord infarction and cerebral infarction: clinical characteristics, and short-term outcome

PubMed Central

Naess, Halvor; Romi, Fredrik

2011-01-01

Background: To compare the clinical characteristics, and short-term outcome of spinal cord infarction and cerebral infarction. Methods: Risk factors, concomitant diseases, neurological deficits on admission, and short-term outcome were registered among 28 patients with spinal cord infarction and 1075 patients with cerebral infarction admitted to the Department of Neurology, Haukeland University Hospital, Bergen, Norway. Multivariate analyses were performed with location of stroke (cord or brain), neurological deficits on admission, and short-term outcome (both Barthel Index [BI] 1 week after symptom onset and discharge home or to other institution) as dependent variables. Results: Multivariate analysis showed that patients with spinal cord infarction were younger, more often female, and less afflicted by hypertension and cardiac disease than patients with cerebral infarction. Functional score (BI) was lower among patients with spinal cord infarctions 1 week after onset of symptoms (P < 0.001). Odds ratio for being discharged home was 5.5 for patients with spinal cord infarction compared to cerebral infarction after adjusting for BI scored 1 week after onset (P = 0.019). Conclusion: Patients with spinal cord infarction have a risk factor profile that differs significantly from that of patients with cerebral infarction, although there are some parallels to cerebral infarction caused by atherosclerosis. Patients with spinal cord infarction were more likely to be discharged home when adjusting for early functional level on multivariate analysis. PMID:21915166

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.

[Effect of local hypothermia on H- and M-responses after spinal cord contusion in dogs].

PubMed

Iafarova, G G; Tumakaev, R F; Khazieva, A R; Baltina, T V

2014-01-01

In this study we investigated a motor-neuronal functional state based on H- and M-responses from m. quadratus plantae in dogs before and after experimental spinal cord contusion with and without following local intraoperative hypothermia. H- and M-responses from m. quadratus plantae were recorded during stimulation of the tibial nerve and results were compared between the groups. Our results demonstrate that local hypothermia applied after spinal cord contusion reduces amplitude of both M- and H-responses and also H(max)/M(max) ratio that may indicate depression of motorneurons excitability. After spinal cord contusion without following hypothermia the excitability of the spinal motorneurons during post-traumatic period, in opposite, was significantly increased. These results support a conclusion that intraoperative hypothermia after spinal cord contusion can delay development of functional excitability of the motoneurons and protect from further changes in H- and M-responses.

White matter organization in cervical spinal cord relates differently to age and control of grip force in healthy subjects.

PubMed

Lindberg, Påvel G; Feydy, Antoine; Maier, Marc A

2010-03-17

Diffusion tensor imaging (DTI) can be used to elucidate relations between CNS structure and function. We hypothesized that the degree of spinal white matter organization relates to the accuracy of control of grip force. Healthy subjects of different age were studied using DTI and visuomotor tracking of precision grip force. The latter is a prime component of manual dexterity. A regional analysis of spinal white matter [fractional anisotropy (FA)] across multiple cervical levels (C2-C3, C4-C5, and C6-C7) and in different regions of interest (left and right lateral or medial spinal cord) was performed. FA was highest at the C2-C3 level, higher on the right than the left side, and higher in the lateral than in the medial spinal cord (p < 0.001). FA of whole cervical spinal cord (C2-C7) was lower in subjects with high tracking error (r = -0.56, p = 0.004) and decreased with age (r = -0.63, p = 0.001). A multiple regression analysis revealed an independent contribution of each predictor (semipartial correlations: age, r = -0.55, p < 0.001; tracking error, r = -0.49, p = 0.003). The closest relation between FA and tracking error was found at the C6-C7 level in the lateral spinal cord, in which the corticospinal tract innervates spinal circuitry controlling hand and digit muscles. FA of the medial spinal cord correlated consistently with age across all cervical levels, whereas FA of the lateral spinal cord did not. The results suggest (1) a functionally relevant specialization of lateral spinal cord white matter and (2) an increased sensitivity to age-related decline in medial spinal cord white matter in healthy subjects.

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.

[Exoskeletons for rehabilitation of patients with spinal cord injuries. Options and limitations].

PubMed

Aach, M; Meindl, R C; Geßmann, J; Schildhauer, T A; Citak, M; Cruciger, O

2015-02-01

Mobile exoskeletons are increasingly being applied in the course of rehabilitation and provision of medical aids to patients with spinal cord injuries. This article gives a description of the currently available exoskeletal systems and the clinical application including scientific and medical evidence, to derive recommendations regarding clinical practice of the various exoskeletons in the rehabilitation of patients with spinal cord injuries. The different systems represent a useful adjunct to the therapeutic regimen depending on the medical objectives. Posture-controlled exoskeletons in particular enable mobilization of patients with neurological gait disorders via direct motion support. In addition the neurologically controlled exoskeleton HAL® leads to functional improvements in patients with residual muscular functions in the chronic phase of spinal cord injury in terms of improved walking abilities subsequent to training. However, beneficial effects on bone density, bladder function and perfusion are conceivable but not yet adequately supported by evidence. Positive effects on spasticity and neuropathic pain are currently based only on case series or small clinical trials. Although exoskeletons are not yet an established tool in the treatment of spinal cord injuries, the systems will play a more important role in rehabilitation of patients with spinal cord injuries in the future. Neurologically controlled exoskeletons show beneficial effects in the treatment of acute and chronic spinal cord injuries and might therefore evolve to be a useful alternative to conventional locomotion training.

Functional magnetic resonance imaging of the human spinal cord during vibration stimulation of different dermatomes.

PubMed

Lawrence, Jane M; Stroman, Patrick W; Kollias, Spyros S

2008-03-01

We investigated noninvasively areas of the healthy human spinal cord that become active in response to vibration stimulation of different dermatomes using functional magnetic resonance imaging (fMRI). The objectives of this study were to: (1) examine the patterns of consistent activity in the spinal cord during vibration stimulation of the skin, and (2) investigate the rostrocaudal distribution of active pixels when stimulation was applied to different dermatomes. FMRI of the cervical and lumbar spinal cord of seven healthy human subjects was carried out during vibration stimulation of six different dermatomes. In separate experiments, vibratory stimulation (about 50 Hz) was applied to the right biceps, wrist, palm, patella, Achilles tendon and left palm. The segmental distribution of activity observed by fMRI corresponded well with known spinal cord neuroanatomy. The peak number of active pixels was observed at the expected level of the spinal cord with some activity in the adjacent segments. The rostrocaudal distribution of activity was observed to correspond to the dermatome being stimulated. Cross-sectional localization of activity was primarily in dorsal areas but also spread into ventral and intermediate areas of the gray matter and a distinct laterality ipsilateral to the stimulated limb was not observed. We demonstrated that fMRI can detect a dermatome-dependent pattern of spinal cord activity during vibratory stimulation and can be used as a passive stimulus for the noninvasive assessment of the functional integrity of the human spinal cord. Demonstration of cross-sectional selectivity of the activation awaits further methodological and experimental refinements.

International spinal cord injury cardiovascular function basic data set.

PubMed

Krassioukov, A; Alexander, M S; Karlsson, A-K; Donovan, W; Mathias, C J; Biering-Sørensen, F

2010-08-01

To create an International Spinal Cord Injury (SCI) Cardiovascular Function Basic Data Set within the framework of the International SCI Data Sets. An international working group. The draft of the data set was developed by a working group comprising members appointed by the American Spinal Injury Association (ASIA), the International Spinal Cord Society (ISCoS) and a representative of the executive committee of the International SCI Standards and Data Sets. The final version of the data set was developed after review by members of the executive committee of the International SCI Standards and Data Sets, the ISCoS scientific committee, ASIA board, relevant and interested international organizations and societies, individual persons with specific interest and the ISCoS Council. To make the data set uniform, each variable and each response category within each variable have been specifically defined in a way that is designed to promote the collection and reporting of comparable minimal data. The variables included in the International SCI Cardiovascular Function Basic Data Set include the following items: date of data collection, cardiovascular history before the spinal cord lesion, events related to cardiovascular function after the spinal cord lesion, cardiovascular function after the spinal cord lesion, medications affecting cardiovascular function on the day of examination; and objective measures of cardiovascular functions, including time of examination, position of examination, pulse and blood pressure. The complete instructions for data collection and the data sheet itself are freely available on the websites of both ISCoS (http://www.iscos.org.uk) and ASIA (http://www.asia-spinalinjury.org).

Comparison of mesenchymal stem cells derived from fat, bone marrow, Wharton's jelly, and umbilical cord blood for treating spinal cord injuries in dogs.

PubMed

Ryu, Hak-Hyun; Kang, Byung-Jae; Park, Sung-Su; Kim, Yongsun; Sung, Gyu-Jin; Woo, Heung-Myong; Kim, Wan Hee; Kweon, Oh-Kyeong

2012-12-01

Previous animal studies have shown that transplantation of mesenchymal stem cells (MSCs) into spinal cord lesions enhances axonal regeneration and promotes functional recovery. We isolated the MSCs derived from fat, bone marrow, Wharton's jelly and umbilical cord blood (UCB) positive for MSC markers and negative for hematopoietic cell markers. Their effects on the regeneration of injured canine spinal cords were compared. Spinal cord injury was induced by balloon catheter compression. Dogs with injured spinal cords were treated with only matrigel or matrigel mixed with each type of MSCs. Olby and modified Tarlov scores, immunohistochemistry, ELISA and Western blot analysis were used to evaluate the therapeutic effects. The different MSC groups showed significant improvements in locomotion at 8 weeks after transplantation (P<0.05). This recovery was accompanied by increased numbers of surviving neuron and neurofilament-positive fibers in the lesion site. Compared to the control, the lesion sizes were smaller, and fewer microglia and reactive astrocytes were found in the spinal cord epicenter of all MSC groups. Although there were no significant differences in functional recovery among the MSCs groups, UCB-derived MSCs (UCSCs) induced more nerve regeneration and anti-inflammation activity (P<0.05). Transplanted MSCs survived for 8 weeks and reduced IL-6 and COX-2 levels, which may have promoted neuronal regeneration in the spinal cord. Our data suggest that transplantation of MSCs promotes functional recovery after SCI. Furthermore, application of UCSCs led to more nerve regeneration, neuroprotection and less inflammation compared to other MSCs.

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

"Low-intensity laser therapy effect on the recovery of traumatic spinal cord injury".

PubMed

Paula, Alecsandra Araujo; Nicolau, Renata Amadei; Lima, Mario de Oliveira; Salgado, Miguel Angel Castillo; Cogo, José Carlos

2014-11-01

Scientific advances have been made to optimize the healing process in spinal cord injury. Studies have been developed to obtain effective treatments in controlling the secondary injury that occurs after spinal cord injury, which substantially changes the prognosis. Low-intensity laser therapy (LILT) has been applied in neuroscience due to its anti-inflammatory effects on biological tissue in the repairing process. Few studies have been made associating LILT to the spinal cord injury. The objective of this study was to investigate the effect of the LILT (GaAlAs laser-780 nm) on the locomotor functional recovery, histomorphometric, and histopathological changes of the spinal cord after moderate traumatic injury in rats (spinal cord injury at T9 and T10). Thirty-one adult Wistar rats were used, which were divided into seven groups: control without surgery (n = 3), control surgery (n = 3), laser 6 h after surgery (n = 5), laser 48 h after surgery (n = 5), medullar lesion (n = 5) without phototherapy, medullar lesion + laser 6 h after surgery (n = 5), and medullar lesion + laser 48 h after surgery (n = 5). The assessment of the motor function was performed using Basso, Beattie, and Bresnahan (BBB) scale and adapted Sciatic Functional Index (aSFI). The assessment of urinary dysfunction was clinically performed. After 21 days postoperative, the animals were euthanized for histological and histomorphometric analysis of the spinal cord. The results showed faster motor evolution in rats with spinal contusion treated with LILT, maintenance of the effectiveness of the urinary system, and preservation of nerve tissue in the lesion area, with a notorious inflammation control and increased number of nerve cells and connections. In conclusion, positive effects on spinal cord recovery after moderate traumatic spinal cord injury were shown after LILT.

In-vivo spinal cord deformation in flexion

NASA Astrophysics Data System (ADS)

Yuan, Qing; Dougherty, Lawrence; Margulies, Susan S.

1997-05-01

Traumatic mechanical loading of the head-neck complex results cervical spinal cord injury when the distortion of the cord is sufficient to produce functional or structural failure of the cord's neural and/or vascular components. Characterizing cervical spinal cord deformation during physiological loading conditions is an important step to defining a comprehensive injury threshold associated with acute spinal cord injury. In this study, in vivo quasi- static deformation of the cervical spinal cord during flexion of the neck in human volunteers was measured using magnetic resonance (MR) imaging of motion with spatial modulation of magnetization (SPAMM). A custom-designed device was built to guide the motion of the neck and enhance more reproducibility. the SPAMM pulse sequence labeled the tissue with a series of parallel tagging lines. A single- shot gradient-recalled-echo sequence was used to acquire the mid-sagittal image of the cervical spine. A comparison of the tagged line pattern in each MR reference and deformed image pair revealed the distortion of the spinal cord. The results showed the cervical spinal cord elongates during head flexion. The elongation experienced by the spinal cord varies linearly with head flexion, with the posterior surface of the cord stretching more than the anterior surface. The maximal elongation of the cord is about 12 percent of its original length.

[Anesthesia for surgery of degenerative and abnormal cervical spine].

PubMed

Béal, J L; Lopin, M C; Binnert, M

1993-01-01

A feature common to all congenital or inflammatory abnormalities of the cervical spine is an actual or potential reduction in the lumen of the spinal canal. The spinal cord and nerve roots are at risk. During intubation, and positioning the patient on the table, all untoward movements of the cervical spine may lead to spinal cord compression. Abnormalities of the cervical spine carry the risk of a difficult intubation. If there is much debate as to what constitutes optimum management of the airway, there is no evidence that any one method is the best. Recognizing the possible instability and intubating with care, are probably much more important in preserving neurological function than any particular mode of intubation. During maintenance of anaesthesia, the main goal is to preserve adequate spinal cord perfusion in order to prevent further damage. Spinal cord blood flow seems to be regulated by the same factors as cerebral blood flow. Hypercapnia increases cord blood flow while hypocapnia decreases it. Therefore, normocapnia or mild hypocapnia is recommended. Induced hypotension is frequently used to decrease blood loss. However, in patients with a marginally perfused spinal cord, the reduction in blood flow may cause ischaemia of the spinal cord and may therefore be relatively contraindicated. In addition to standard intraoperative monitoring, spinal cord monitoring is almost mandatory. Monitoring somatosensory evoked potentials is used routinely. However, the major limitation is that this technique only monitors dorsal column function; theoretically, motor paralysis can occur despite a lack of change in recorded signals. Neurogenic motor evoked potentials may now be used to monitor anterior spinal cord integrity.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Cellular Scaling Rules for Primate Spinal Cords

PubMed Central

Burish, Mark J.; Peebles, J. Klint; Baldwin, Mary K.; Tavares, Luciano; Kaas, Jon H.; Herculano-Houzel, Suzana

2010-01-01

The spinal cord can be considered a major sensorimotor interface between the body and the brain. How does the spinal cord scale with body and brain mass, and how are its numbers of neurons related to the number of neurons in the brain across species of different body and brain sizes? Here we determine the cellular composition of the spinal cord in eight primate species and find that its number of neurons varies as a linear function of cord length, and accompanies body mass raised to an exponent close to 1/3. This relationship suggests that the extension, mass and number of neurons that compose the spinal cord are related to body length, rather than to body mass or surface. Moreover, we show that although brain mass increases linearly with cord mass, the number of neurons in the brain increases with the number of neurons in the spinal cord raised to the power of 1.7. This faster addition of neurons to the brain than to the spinal cord is consistent with current views on how larger brains add complexity to the processing of environmental and somatic information. PMID:20926855

Targeting L-Selectin to Improve Neurologic and Urologic Function After Spinal Cord Injury

DTIC Science & Technology

2015-10-01

demonstrated locomotor recovery in mice receiving 40mg/kg DFA up to 3 hours following spinal cord injury -We demonstrated improved locomotor recovery...health, as evaluated by body weight -We identified no added locomotor recovery due to multiple, successive doses of DFA. Moreover, additional doses...bladder function Significance: We have identified robust locomotor recovery in both mild and severe spinal cord injured mice that received DFA up

Recurrent ‘universal tumour’ of the spinal cord

PubMed Central

O'Grady, John; Kaliaperumal, Chandrasekaran; O'Sullivan, Michael

2012-01-01

Lipoma is popularly known as the ‘universal tumour’ because of its ubiquitous presence anywhere in the body. This is the first documented case of recurrent thoracic spinal cord intramedullary lipoma in a 44-year-old man, with a background of spinal dysraphism, which recurred 15 years after initial surgery. He was followed up every 2 years and currently presented with an 8-month history of progressive weakness in his lower limbs. An MRI of the spine confirmed recurrence of lipoma. He underwent redo laminectomy and partial resection and spinal cord decompression with duroplasty. Lipoma, although a low-grade tumour, can cause significant neurological deficits because of its location. Surgical exploration and removal of lipoma is recommended. However, to preserve the functionality of the spinal cord, one may resort to partial resection and aim for spinal cord decompression. The literature on spinal cord lipoma is reviewed and the aetiopathogenesis of this rare occurrence is described. PMID:22675149

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.

TEMPORAL NEUROTRANSMITTER CONDITIONING RESTORES THE FUNCTIONAL ACTIVITY OF ADULT SPINAL-CORD NEURONS IN LONG-TERM CULTURE

PubMed Central

Das, Mainak; Bhargava, Neelima; Bhalkikar, Abhijeet; Kang, Jung Fong; Hickman, James J

2008-01-01

The ability to culture functional adult mammalian spinal-cord neurons represents an important step in the understanding and treatment of a spectrum of neurological disorders including spinal cord injury. Previously, the limited functional recovery of these cells, as characterized by a diminished ability to initiate action potentials and to exhibit repetitive firing patterns, has arisen as a major impediment to their physiological relevance. In this report we demonstrate that single temporal doses of the neurotransmitters serotonin, glutamate (N-acetyl-DL-glutamic acid) and acetylcholine-chloride leads to the full electrophysiological functional recovery of adult mammalian spinal-cord neurons, when they are cultured under defined serum-free conditions. Approximately 60% of the neurons treated regained their electrophysiological signature, often firing single, double and, most importantly, multiple action potentials. PMID:18005959

A PET/CT approach to spinal cord metabolism in amyotrophic lateral sclerosis.

PubMed

Marini, Cecilia; Cistaro, Angelina; Campi, Cristina; Calvo, Andrea; Caponnetto, Claudia; Nobili, Flavio Mariano; Fania, Piercarlo; Beltrametti, Mauro C; Moglia, Cristina; Novi, Giovanni; Buschiazzo, Ambra; Perasso, Annalisa; Canosa, Antonio; Scialò, Carlo; Pomposelli, Elena; Massone, Anna Maria; Bagnara, Maria Caludia; Cammarosano, Stefania; Bruzzi, Paolo; Morbelli, Silvia; Sambuceti, Gianmario; Mancardi, Gianluigi; Piana, Michele; Chiò, Adriano

2016-10-01

In amyotrophic lateral sclerosis, functional alterations within the brain have been intensively assessed, while progression of lower motor neuron damage has scarcely been defined. The aim of the present study was to develop a computational method to systematically evaluate spinal cord metabolism as a tool to monitor disease mechanisms. A new computational three-dimensional method to extract the spinal cord from (18)F-FDG PET/CT images was evaluated in 30 patients with spinal onset amyotrophic lateral sclerosis and 30 controls. The algorithm identified the skeleton on the CT images by using an extension of the Hough transform and then extracted the spinal canal and the spinal cord. In these regions, (18)F-FDG standardized uptake values were measured to estimate the metabolic activity of the spinal canal and cord. Measurements were performed in the cervical and dorsal spine and normalized to the corresponding value in the liver. Uptake of (18)F-FDG in the spinal cord was significantly higher in patients than in controls (p < 0.05). By contrast, no significant differences were observed in spinal cord and spinal canal volumes between the two groups. (18)F-FDG uptake was completely independent of age, gender, degree of functional impairment, disease duration and riluzole treatment. Kaplan-Meier analysis showed a higher mortality rate in patients with standardized uptake values above the fifth decile at the 3-year follow-up evaluation (log-rank test, p < 0.01). The independence of this value was confirmed by multivariate Cox analysis. Our computational three-dimensional method enabled the evaluation of spinal cord metabolism and volume and might represent a potential new window onto the pathophysiology of amyotrophic lateral sclerosis.

Transplantation of human embryonic stem cell-derived oligodendrocyte progenitors into rat spinal cord injuries does not cause harm.

PubMed

Cloutier, Frank; Siegenthaler, Monica M; Nistor, Gabriel; Keirstead, Hans S

2006-07-01

Demyelination contributes to loss of function following spinal cord injury. We have shown previously that transplantation of human embryonic stem cell-derived oligodendrocyte progenitors into adult rat 200 kD contusive spinal cord injury sites enhances remyelination and promotes recovery of motor function. Previous studies using oligodendrocyte lineage cells have noted a correlation between the presence of demyelinating pathology and the survival and migration rate of the transplanted cells. The present study compared the survival and migration of human embryonic stem cell-derived oligodendrocyte progenitors injected 7 days after a 200 or 50 kD contusive spinal cord injury, as well as the locomotor outcome of transplantation. Our findings indicate that a 200 kD spinal cord injury induces extensive demyelination, whereas a 50 kD spinal cord injury induces no detectable demyelination. Cells transplanted into the 200 kD injury group survived, migrated, and resulted in robust remyelination, replicating our previous studies. In contrast, cells transplanted into the 50 kD injury group survived, exhibited limited migration, and failed to induce remyelination as demyelination in this injury group was absent. Animals that received a 50 kD injury displayed only a transient decline in locomotor function as a result of the injury. Importantly, human embryonic stem cell-derived oligodendrocyte progenitor transplants into the 50 kD injury group did not cause a further decline in locomotion. Our studies highlight the importance of a demyelinating pathology as a prerequisite for the function of transplanted myelinogenic cells. In addition, our results indicate that transplantation of human embryonic stem cell-derived oligodendrocyte progenitor cells into the injured spinal cord is not associated with a decline in locomotor function.

Is neuroinflammation in the injured spinal cord different than in the brain? Examining intrinsic differences between the brain and spinal cord.

PubMed

Zhang, B; Gensel, J C

2014-08-01

The field of neuroimmunology is rapidly advancing. There is a growing appreciation for heterogeneity, both in inflammatory composition and region-specific inflammatory responses. This understanding underscores the importance of developing targeted immunomodulatory therapies for treating neurological disorders. Concerning neurotrauma, there is a dearth of publications directly comparing inflammatory responses in the brain and spinal cord after injury. The question therefore remains as to whether inflammatory cells responding to spinal cord vs. brain injury adopt similar functions and are therefore amenable to common therapies. In this review, we address this question while revisiting and modernizing the conclusions from publications that have directly compared inflammation across brain and spinal cord injuries. By examining molecular differences, anatomical variations, and inflammatory cell phenotypes between the injured brain and spinal cord, we provide insight into how neuroinflammation relates to neurotrauma and into fundamental differences between the brain and spinal cord. Copyright © 2014 Elsevier Inc. All rights reserved.

Monitoring somatosensory evoked potentials in spinal cord ischemia-reperfusion injury

PubMed Central

Ji, Yiming; Meng, Bin; Yuan, Chenxi; Yang, Huilin; Zou, Jun

2013-01-01

It remains unclear whether spinal cord ischemia-reperfusion injury caused by ischemia and other non-mechanical factors can be monitored by somatosensory evoked potentials. Therefore, we monitored spinal cord ischemia-reperfusion injury in rabbits using somatosensory evoked potential detection technology. The results showed that the somatosensory evoked potential latency was significantly prolonged and the amplitude significantly reduced until it disappeared during the period of spinal cord ischemia. After reperfusion for 30–180 minutes, the amplitude and latency began to gradually recover; at 360 minutes of reperfusion, the latency showed no significant difference compared with the pre-ischemic value, while the somatosensory evoked potential amplitude in-creased, and severe hindlimb motor dysfunctions were detected. Experimental findings suggest that changes in somatosensory evoked potential latency can reflect the degree of spinal cord ischemic injury, while the amplitude variations are indicators of the late spinal cord reperfusion injury, which provide evidence for the assessment of limb motor function and avoid iatrogenic spinal cord injury. PMID:25206629

The impact of pain on spiritual well-being in people with a spinal cord injury.

PubMed

Siddall, P J; McIndoe, L; Austin, P; Wrigley, P J

2017-01-01

The study uses a cross-sectional, group comparison, questionnaire-based design. To determine whether spinal cord injury and pain have an impact on spiritual well-being and whether there is an association between spiritual well-being and measures of pain and psychological function. University teaching hospital in Sydney, New South Wales, Australia. Questionnaires evaluating pain, psychological and spiritual well-being were administered to a group of people with a spinal cord injury (n=53) and a group without spinal cord injury (n=37). Spiritual well-being was assessed using the Functional Assessment of Chronic Illness and Therapy - Spirituality Extended Scale (FACIT-Sp-Ex). Pain and psychological function were also assessed using standard, validated measures of pain intensity, pain interference, mood and cognition. Levels of spiritual well-being in people with a spinal cord injury were significantly lower when compared with people without a spinal cord injury. In addition, there was a moderate but significant negative correlation between spiritual well-being and pain intensity. There was also a strong and significant negative correlation between depression and spiritual well-being and a strong and significant positive correlation between spiritual well-being and both pain self-efficacy and satisfaction with life. Consequences of a spinal cord injury include increased levels of spiritual distress, which is associated, with higher levels of pain and depression and lower levels of pain self-efficacy and satisfaction with life. These findings indicate the importance of addressing spiritual well-being as an important component in the long-term rehabilitation of any person following spinal cord injury. This study was supported by grant funding from the Australian and New Zealand College of Anaesthetists, and the National Health and Medical Research Council of Australia.

Adenosine A1-Dopamine D1 Receptor Heteromers Control the Excitability of the Spinal Motoneuron.

PubMed

Rivera-Oliver, Marla; Moreno, Estefanía; Álvarez-Bagnarol, Yocasta; Ayala-Santiago, Christian; Cruz-Reyes, Nicole; Molina-Castro, Gian Carlo; Clemens, Stefan; Canela, Enric I; Ferré, Sergi; Casadó, Vicent; Díaz-Ríos, Manuel

2018-05-24

While the role of the ascending dopaminergic system in brain function and dysfunction has been a subject of extensive research, the role of the descending dopaminergic system in spinal cord function and dysfunction is just beginning to be understood. Adenosine plays a key role in the inhibitory control of the ascending dopaminergic system, largely dependent on functional complexes of specific subtypes of adenosine and dopamine receptors. Combining a selective destabilizing peptide strategy with a proximity ligation assay and patch-clamp electrophysiology in slices from male mouse lumbar spinal cord, the present study demonstrates the existence of adenosine A 1 -dopamine D 1 receptor heteromers in the spinal motoneuron by which adenosine tonically inhibits D 1 receptor-mediated signaling. A 1 -D 1 receptor heteromers play a significant control of the motoneuron excitability, represent main targets for the excitatory effects of caffeine in the spinal cord and can constitute new targets for the pharmacological therapy after spinal cord injury, motor aging-associated disorders and restless legs syndrome.

Assessment of abdominal muscle function in individuals with motor-complete spinal cord injury above T6 in response to transcranial magnetic stimulation.

PubMed

Bjerkefors, Anna; Squair, Jordan W; Chua, Romeo; Lam, Tania; Chen, Zhen; Carpenter, Mark G

2015-02-01

To use transcranial magnetic stimulation and electromyography to assess the potential for preserved function in the abdominal muscles in individuals classified with motor-complete spinal cord injury above T6. Five individuals with spinal cord injury (C5-T3) and 5 able-bodied individuals. Transcranial magnetic stimulation was delivered over the abdominal region of primary motor cortex during resting and sub-maximal (or attempted) contractions. Surface electromyography was used to record motor-evoked potentials as well as maximal voluntary (or attempted) contractions in the abdominal muscles and the diaphragm. Responses to transcranial magnetic stimulation in the abdominal muscles occurred in all spinal cord injury subjects. Latencies of muscle response onsets were similar in both groups; however, peak-to-peak amplitudes were smaller in the spinal cord injury group. During maximal voluntary (or attempted) contractions all spinal cord injury subjects were able to elicit electromyography activity above resting levels in more than one abdominal muscle across tasks. Individuals with motor-complete spinal cord injury above T6 were able to activate abdominal muscles in response to transcranial magnetic stimulation and during maximal voluntary (or attempted) contractions. The activation was induced directly through corticospinal pathways, and not indirectly by stretch reflex activations of the diaphragm. Transcranial magnetic stimulation and electromyography measurements provide a useful method to assess motor preservation of abdominal muscles in persons with spinal cord injury.

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.

Retraining the injured spinal cord

NASA Technical Reports Server (NTRS)

Edgerton, V. R.; Leon, R. D.; Harkema, S. J.; Hodgson, J. A.; London, N.; Reinkensmeyer, D. J.; Roy, R. R.; Talmadge, R. J.; Tillakaratne, N. J.; Timoszyk, W.;

Assessing forelimb function after unilateral cervical spinal cord injury: novel forelimb tasks predict lesion severity and recovery.

PubMed

Khaing, Zin Z; Geissler, Sydney A; Jiang, Shan; Milman, Brian D; Aguilar, Sandra V; Schmidt, Christine E; Schallert, Timothy

2012-02-10

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. Recently there has been increasing interest in cervical spinal cord injury models because the majority of spinal cord injuries are at cervical levels. Here we examined spontaneous functional recovery of adult rats with either laminectomy or lateral hemisection of the cervical spinal cord at C3-C4. Behavioral tests were carried out, including the forelimb locomotor scale (FLS), a postural instability test (PIT), a pasta-handling test that has been used to assess forepaw digit function and latency to eat, forelimb use during vertical-lateral wall exploration in a cylindrical enclosure, and vibrissae-elicited forelimb placing tests. In addition, a forelimb step-alternation test was developed to assess functional recovery at 12 weeks post-injury. All tests detected cSCI-induced deficits relative to laminectomy. Interestingly, the severity of deficits in the forelimb step-alternation test was associated with more extensive spinal damage, greater impairment, and less recovery in the FLS and other tests. For the pasta-handling test we found that rats with a milder cervical injury (alternators) were more likely to use both forepaws together compared to rats with a more severe injury (non-alternators). In addition, using the PIT, we detected enhanced function of the good limb, suggesting that neural plasticity on the unaffected side of the spinal cord may have occurred to compensate for deficits in the impaired forelimb. These outcome measures should be useful for investigating neural events associated with cSCI, and for developing novel treatment strategies.

Spinal Cord Ischemia Secondary to Hypovolemic Shock

PubMed Central

Kapoor, Siddhant; Koh, Roy KM; Yang, Eugene WR; Hee, Hwan-Tak

2014-01-01

A 44-year-old male presented with symptoms of spinal cord compression secondary to metastatic prostate cancer. An urgent decompression at the cervical-thoracic region was performed, and there were no complications intraoperatively. Three hours postoperatively, the patient developed acute bilateral lower-limb paralysis (motor grade 0). Clinically, he was in class 3 hypovolemic shock. An urgent magnetic resonance imaging (MRI) was performed, showing no epidural hematoma. He was managed aggressively with medical therapy to improve his spinal cord perfusion. The patient improved significantly, and after one week, he was able to regain most of his motor functions. Although not commonly reported, spinal cord ischemia post-surgery should be recognized early, especially in the presence of hypovolemic shock. MRI should be performed to exclude other potential causes of compression. Spinal cord ischemia needs to be managed aggressively with medical treatment to improve spinal cord perfusion. The prognosis depends on the severity of deficits, and is usually favorable. PMID:25558328

Activity-Based Therapies To Promote Forelimb Use after a Cervical Spinal Cord Injury

PubMed Central

Dai, Haining; MacArthur, Linda; McAtee, Marietta; Hockenbury, Nicole; Tidwell, J. Lille; McHugh, Brian; Mansfield, Kevin; Finn, Tom; Hamers, Frank P.T.

2009-01-01

Abstract Significant interest exists in strategies for improving forelimb function following spinal cord injury. We investigated the effect of enriched housing combined with skilled training on the recovery of skilled and automatic forelimb function after a cervical spinal cord injury in adult rats. All animals were pretrained in skilled reaching, gridwalk crossing, and overground locomotion. Some received a cervical over-hemisection lesion at C4-5, interrupting the right side of the spinal cord and dorsal columns bilaterally, and were housed in standard housing alone or enriched environments with daily training. A subset of animals received rolipram to promote neuronal plasticity. Animals were tested weekly for 4 weeks to measure reaching, errors on the gridwalk, locomotion, and vertical exploration. Biotinylated dextran amine was injected into the cortex to label the corticospinal tract. Enriched environments/daily training significantly increased the number and success of left reaches compared to standard housing. Animals also made fewer errors on the gridwalk, a measure of coordinated forelimb function. However, there were no significant improvements in forelimb use during vertical exploration or locomotion. Likewise, rolipram did not improve any of the behaviors tested. Both enriched housing and rolipram increased plasticity of the corticospinal tract rostral to the lesion. These studies indicate that skilled training after a cervical spinal cord injury improves recovery of skilled forelimb use (reaching) and coordinated limb function (gridwalk) but does not improve automatic forelimb function (locomotion and vertical exploration). These studies suggest that rehabilitating forelimb function after spinal cord injury will require separate strategies for descending and segmental pathways. PMID:19317604

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.

[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.

Clinical, magnetic resonance imaging, and histopathologic findings in 6 dogs with surgically resected extraparenchymal spinal cord hematomas.

PubMed

Hague, D W; Joslyn, S; Bush, W W; Glass, E N; Durham, A C

2015-01-01

Extraparenchymal spinal cord hematoma has been described in veterinary medicine in association with neoplasia, intervertebral disk disease, and snake envenomation. There are rare reports of spontaneous extraparenchymal spinal cord hematoma formation with no known cause in human medicine. Multiple cases of spontaneous extraparenchymal spinal cord hematoma have not been described previously in veterinary medicine. To describe the signalment, clinical findings, magnetic resonance imaging (MRI) features, and surgical outcomes in histopathologically confirmed extraparenchymal spinal cord hematomas in dogs with no identified underlying etiology. Six dogs had MRI of the spinal cord, decompressive spinal surgery, and histopathologic confirmation of extraparenchymal spinal cord hematoma not associated with an underlying cause. Multi-institutional retrospective study. Six patients had spontaneous extraparenchymal spinal cord hematoma formation. MRI showed normal signal within the spinal cord parenchyma in all patients. All hematomas had T2-weighted hyperintensity and the majority (5/6) had no contrast enhancement. All dogs underwent surgical decompression and most patients (5/6) returned to normal or near normal neurologic function postoperatively. Follow-up of the patients (ranging between 921 and 1,446 days) showed no progression of neurologic clinical signs or any conditions associated with increased bleeding tendency. Before surgery and histopathology confirming extraparenchymal hematoma, the primary differential in most cases was neoplasia, based on the MRI findings. This retrospective study reminds clinicians of the importance of the combination of advanced imaging combined with histopathologic diagnosis. The prognosis for spontaneous spinal cord extraparenchymal hematoma with surgical decompression appears to be favorable in most cases. Copyright © 2015 by the American College of Veterinary Internal Medicine.

The temporal profile of the reaction of microglia, astrocytes, and macrophages in the delayed onset paraplegia after transient spinal cord ischemia in rabbits.

PubMed

Matsumoto, Satoshi; Matsumoto, Mishiya; Yamashita, Atsuo; Ohtake, Kazunobu; Ishida, Kazuyoshi; Morimoto, Yasuhiro; Sakabe, Takefumi

2003-06-01

In the present study, we sought to elucidate the temporal profile of the reaction of microglia, astrocytes, and macrophages in the progression of delayed onset motor dysfunction after spinal cord ischemia (15 min) in rabbits. At 2, 4, 8, 12, 24, and 48 h after reperfusion (9 animals in each), hind limb motor function was assessed, and the lumbar spinal cord was histologically examined. Delayed motor dysfunction was observed in most animals at 48 h after ischemia, which could be predicted by a poor recovery of segmental spinal cord evoked potentials at 15 min of reperfusion. In the gray matter of the lumbar spinal cord, both microglia and astrocytes were activated early (2 h) after reperfusion. Microglia were diffusely activated and engulfed motor neurons irrespective of the recovery of segmental spinal cord evoked potentials. In contrast, early astrocytic activation was confined to the area where neurons started to show degeneration. Macrophages were first detected at 8 h after reperfusion and mainly surrounded the infarction area later. Although the precise roles of the activation of microglia, astrocytes, and macrophages are to be further determined, the results indicate that understanding functional changes of astrocytes may be important in the mechanism of delayed onset motor dysfunction including paraplegia. Microglia and macrophages play a role in removing tissue debris after transient spinal cord ischemia. Disturbance of astrocytic defense mechanism, breakdown of the blood-spinal cord barrier, or both seemed to be involved in the development of delayed motor dysfunction.

Patient-focused goal planning process and outcome after spinal cord injury rehabilitation: quantitative and qualitative audit.

PubMed

Byrnes, Michelle; Beilby, Janet; Ray, Patricia; McLennan, Renee; Ker, John; Schug, Stephan

2012-12-01

To evaluate the process and outcome of a multidisciplinary inpatient goal planning rehabilitation programme on physical, social and psychological functioning for patients with spinal cord injury. Clinical audit: quantitative and qualitative analyses. Specialist spinal injury unit, Perth, Australia. Consecutive series of 100 newly injured spinal cord injury inpatients. MAIN MEASURE(S): The Needs Assessment Checklist (NAC), patient-focused goal planning questionnaire and goal planning progress form. The clinical audit of 100 spinal cord injured patients revealed that 547 goal planning meetings were held with 8531 goals stipulated in total. Seventy-five per cent of the goals set at the first goal planning meeting were achieved by the second meeting and the rate of goal achievements at subsequent goal planning meetings dropped to 56%. Based on quantitative analysis of physical, social and psychological functioning, the 100 spinal cord injury patients improved significantly from baseline to discharge. Furthermore, qualitative analysis revealed benefits consistently reported by spinal cord injury patients of the goal planning rehabilitation programme in improvements to their physical, social and psychological adjustment to injury. The findings of this clinical audit underpin the need for patient-focused goal planning rehabilitation programmes which are tailored to the individual's needs and involve a comprehensive multidisciplinary team.

Fertility and sexuality in the spinal cord injury patient.

PubMed

Stoffel, J T; Van der Aa, F; Wittmann, D; Yande, S; Elliott, S

2018-06-14

After a spinal cord injury, patients have different perceptions of sexuality, sexual function, and potential for fertility. These changes can greatly impact quality of life over a lifetime. The purpose of this workgroup was to identify common evidence based or expert opinion themes and recommendations regarding treatment of sexuality, sexual function and fertility in the spinal cord injury population. As part of the SIU-ICUD joint consultation of Urologic Management of the Spinal Cord Injury (SCI), a workgroup and comprehensive literature search of English language manuscripts regarding fertility and sexuality in the spinal cord injury patient were formed. Articles were compiled, and recommendations in the chapter are based on group discussion and follow the Oxford Centre for Evidence-based Medicine system for levels of evidence (LOEs) and grades of recommendation (GORs). Genital arousal, ejaculation, and orgasm are significantly impacted after spinal cord injury in both male and female SCI patients. This may have a more significant impact on potential for fertility in male spinal cord injury patients, particularly regarding ability of generate erection, semen quantity and quality. Female patients should be consulted that pregnancy is still possible after injury and a woman should expect resumption of normal reproductive function. As a result, sexual health teaching should be continued in women despite injury. Pregnancy in a SCI may cause complications such as autonomic dysreflexia, so this group should be carefully followed during pregnancy. By understanding physiologic changes after injury, patients and care teams can work together to achieve goals and maximize sexual quality of life after the injury.

Multimodal intraoperative monitoring: an overview and proposal of methodology based on 1,017 cases

PubMed Central

Eggspuehler, Andreas; Muller, Alfred; Dvorak, Jiri

2007-01-01

To describe different currently available tests of multimodal intraoperative monitoring (MIOM) used in spine and spinal cord surgery indicating the technical parameters, application and interpretation as an easy understanding systematic overview to help implementation of MIOM and improve communication between neurophysiologists and spine surgeons. This article aims to give an overview and proposal of the different MIOM-techniques as used daily in spine and spinal cord surgery at our institution. Intensive research in neurophysiology over the past decades has lead to a profound understanding of the spinal cord, nerve functions and their intraoperative functional evaluation in anaesthetised patients. At present, spine surgeons and neurophysiologist are faced with 1,883 publications in PubMed on spinal cord monitoring. The value and the limitations of single monitoring methods are well documented. The diagnostic power of the multimodal approach in a larger study population in spine surgery, as measured with sensitivity and specificity, is dealt with elsewhere in this supplement (Sutter et al. in Eur Spine J Suppl, 2007). This paper aims to give a detailed description of the different modalities used in this study. Description of monitoring techniques of the descending and ascending spinal cord and nerve root pathways by motor evoked potentials of the spinal cord and muscles elicited after transcranial electrical motor cortex, spinal cord, cauda equina and nerve root stimulation, continuous EMG, sensory cortical and spinal evoked potentials, as well as direct spinal cord evoked potentials applied on 1,017 patients. The method of MIOM, continuously adapted according to the site, stage of surgery and potential danger to nerve tissues, proved to be applicable with online results, reliable and furthermore teachable. PMID:17653777

Ex Vivo Diffusion Tensor Imaging of Spinal Cord Injury in Rats of Varying Degrees of Severity

PubMed Central

Jirjis, Michael B.; Kurpad, Shekar N.

2013-01-01

Abstract The aim of this study was to characterize magnetic resonance diffusion tensor imaging (DTI) in proximal regions of the spinal cord following a thoracic spinal cord injury (SCI). Sprague–Dawley rats (n=40) were administered a control, mild, moderate, or severe contusion injury at the T8 vertebral level. Six direction diffusion weighted images (DWIs) were collected ex vivo along the length of the spinal cord, with an echo/repetition time of 31.6 ms/14 sec and b=500 sec/mm2. Diffusion metrics were correlated to hindlimb motor function. Significant differences were found for whole cord region of interest (ROI) drawings for fractional anisotropy (FA), mean diffusivity (MD), longitudinal diffusion coefficient (LD), and radial diffusion coefficient (RD) at each of the cervical levels (p<0.01). Motor function correlated with MD in the cervical segments of the spinal cord (r2=0.80). The diffusivity of water significantly decreased throughout “uninjured” portions of the spinal cord following a contusion injury (p<0.05). Diffusivity metrics were found to be altered following SCI in both white and gray matter regions. Injury severity was associated with diffusion changes over the entire length of the cord. This study demonstrates that DTI is sensitive to SCI in regions remote from injury, suggesting that the diffusion metrics may be used as a biomarker for severity of injury. PMID:23782233

Improving Survival and Promoting Respiratory Motor Function after Cervical Spinal Cord Injury

DTIC Science & Technology

2016-09-01

AWARD NUMBER: W81XWH-15-1-0378 TITLE: Improving Survival and Promoting Respiratory Motor Function after Cervical Spinal Cord Injury PRINCIPAL...Aug 2015 - 14 Aug 2016 4. TITLE AND SUBTITLE CordCorInjury 5a. CONTRACT NUMBER Improvi g Survival and Promoting Respiratory Motor Function After... respiratory complications. This application proposes to help improve survival, decrease early dependence on mechanical ventilation, and restore breathing

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.

Towards a miniaturized brain-machine-spinal cord interface (BMSI) for restoration of function after spinal cord injury.

PubMed

Shahdoost, Shahab; Frost, Shawn; Van Acker, Gustaf; DeJong, Stacey; Dunham, Caleb; Barbay, Scott; Nudo, Randolph; Mohseni, Pedram

2014-01-01

Nearly 6 million people in the United States are currently living with paralysis in which 23% of the cases are related to spinal cord injury (SCI). Miniaturized closed-loop neural interfaces have the potential for restoring function and mobility lost to debilitating neural injuries such as SCI by leveraging recent advancements in bioelectronics and a better understanding of the processes that underlie functional and anatomical reorganization in an injured nervous system. This paper describes our current progress towards developing a miniaturized brain-machine-spinal cord interface (BMSI) that is envisioned to convert in real time the neural command signals recorded from the brain to electrical stimuli delivered to the spinal cord below the injury level. Specifically, the paper reports on a corticospinal interface integrated circuit (IC) as a core building block for such a BMSI that is capable of low-noise recording of extracellular neural spikes from the cerebral cortex as well as muscle activation using intraspinal microstimulation (ISMS) in a rat with contusion injury to the thoracic spinal cord. The paper further presents results from a neurobiological study conducted in both normal and SCI rats to investigate the effect of various ISMS parameters on movement thresholds in the rat hindlimb. Coupled with proper signal-processing algorithms in the future for the transformation between the cortically recorded data and ISMS parameters, such a BMSI has the potential to facilitate functional recovery after an SCI by re-establishing corticospinal communication channels lost due to the injury.

Muscle spindle feedback directs locomotor recovery and circuit reorganization after spinal cord injury.

PubMed

Takeoka, Aya; Vollenweider, Isabel; Courtine, Grégoire; Arber, Silvia

2014-12-18

Spinal cord injuries alter motor function by disconnecting neural circuits above and below the lesion, rendering sensory inputs a primary source of direct external drive to neuronal networks caudal to the injury. Here, we studied mice lacking functional muscle spindle feedback to determine the role of this sensory channel in gait control and locomotor recovery after spinal cord injury. High-resolution kinematic analysis of intact mutant mice revealed proficient execution in basic locomotor tasks but poor performance in a precision task. After injury, wild-type mice spontaneously recovered basic locomotor function, whereas mice with deficient muscle spindle feedback failed to regain control over the hindlimb on the lesioned side. Virus-mediated tracing demonstrated that mutant mice exhibit defective rearrangements of descending circuits projecting to deprived spinal segments during recovery. Our findings reveal an essential role for muscle spindle feedback in directing basic locomotor recovery and facilitating circuit reorganization after spinal cord injury. Copyright © 2014 Elsevier Inc. All rights reserved.

Ecto-domain phosphorylation promotes functional recovery from spinal cord injury

PubMed Central

Suehiro, Kenji; Nakamura, Yuka; Xu, Shuai; Uda, Youichi; Matsumura, Takafumi; Yamaguchi, Yoshiaki; Okamura, Hitoshi; Yamashita, Toshihide; Takei, Yoshinori

2014-01-01

Inhibition of Nogo-66 receptor (NgR) can promote recovery following spinal cord injury. The ecto-domain of NgR can be phosphorylated by protein kinase A (PKA), which blocks activation of the receptor. Here, we found that infusion of PKA plus ATP into the damaged spinal cord can promote recovery of locomotor function. While significant elongation of cortical-spinal axons was not detectable even in the rats showing enhanced recovery, neuronal precursor cells were observed in the region where PKA plus ATP were directly applied. NgR1 was expressed in neural stem/progenitor cells (NSPs) derived from the adult spinal cord. Both an NgR1 antagonist NEP1-40 and ecto-domain phosphorylation of NgR1 promote neuronal cell production of the NSPs, in vitro. Thus, inhibition of NgR1 in NSPs can promote neuronal cell production, which could contribute to the enhanced recovery of locomotor function following infusion of PKA and ATP. PMID:24826969

Discrimination of heterogenous mRNAs encoding strychnine-sensitive glycine receptors in Xenopus oocytes by antisense oligonucleotides.

PubMed Central

Akagi, H; Patton, D E; Miledi, R

1989-01-01

Three synthetic oligodeoxynucleotides complementary to different parts of an RNA encoding a glycine receptor subunit were used to discriminate heterogenous mRNAs coding for glycine receptors in adult and neonatal rat spinal cord. Injection of the three antisense oligonucleotides into Xenopus oocytes specifically inhibited the expression of glycine receptors by adult spinal cord mRNA. In contrast, the antisense oligonucleotides were much less potent in inhibiting the expression of glycine receptors encoded by neonatal spinal cord mRNA. Northern blot analysis revealed that the oligonucleotides hybridized mostly to an adult cord transcript of approximately 10 kilobases in size. This band was also present in neonatal spinal cord mRNA but its density was about one-fourth of the adult cord message. There was no intense band in the low molecular weight position (approximately 2 kilobases), the existence of which was expected from electrophysiological studies with size-fractionated mRNA of neonatal spinal cord. Our results suggest that in the rat spinal cord there are at least three different types of mRNAs encoding functional strychnine-sensitive glycine receptors. Images PMID:2479016

Motor Control of Human Spinal Cord Disconnected from the Brain and Under External Movement.

PubMed

Mayr, Winfried; Krenn, Matthias; Dimitrijevic, Milan R

2016-01-01

Motor control after spinal cord injury is strongly depending on residual ascending and descending pathways across the lesion. The individually altered neurophysiology is in general based on still intact sublesional control loops with afferent sensory inputs linked via interneuron networks to efferent motor outputs. Partial or total loss of translesional control inputs reduces and alters the ability to perform voluntary movements and results in motor incomplete (residual voluntary control of movement functions) or motor complete (no residual voluntary control) spinal cord injury classification. Of particular importance are intact functionally silent neural structures with residual brain influence but reduced state of excitability that inhibits execution of voluntary movements. The condition is described by the term discomplete spinal cord injury. There are strong evidences that artificial afferent input, e.g., by epidural or noninvasive electrical stimulation of the lumbar posterior roots, can elevate the state of excitability and thus re-enable or augment voluntary movement functions. This modality can serve as a powerful assessment technique for monitoring details of the residual function profile after spinal cord injury, as a therapeutic tool for support of restoration of movement programs and as a neuroprosthesis component augmenting and restoring movement functions, per se or in synergy with classical neuromuscular or muscular electrical stimulation.

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.

Neuromodulation of the neural circuits controlling the lower urinary tract

PubMed Central

Gad, Parag N.; Roy, Roland R.; Zhong, Hui; Gerasimenko, Yury P.; Taccola, Giuliano; Edgerton, V. Reggie

2017-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Herein we demonstrate that electrically evoked potentials in the hindlimb muscles and external urethral sphincter are modulated uniquely when the rat is stepping bipedally and not voiding, immediately pre-voiding, or when voiding. We also show that spinal cord stimulation can effectively neuromodulate the lower urinary tract via frequency-dependent stimulation patterns and that neural peripheral nerve stimulation can activate the external urethral sphincter both directly and via relays in the spinal cord. The data demonstrate that the sensorimotor networks controlling bladder and locomotion are highly integrated neurophysiologically and behaviorally and demonstrate how these two functions are modulated by sensory input from the tibial and pudental nerves. A more detailed understanding of the high level of interaction between these networks could lead to the integration of multiple neurophysiological strategies to improve bladder function. These data suggest that the development of strategies to improve bladder function should simultaneously engage these highly integrated networks in an activity-dependent manner. PMID:27381425

Transplantation of canine umbilical cord blood-derived mesenchymal stem cells in experimentally induced spinal cord injured dogs.

PubMed

Lim, Ji Hey; Byeon, Ye Eun; Ryu, Hak Hyun; Jeong, Yun Hyeok; Lee, Young Won; Kim, Wan Hee; Kang, Kyung Sun; Kweon, Oh Kyeong

2007-09-01

This study was to determine the effects of allogenic umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) and recombinant methionyl human granulocyte colony-stimulating factor (rmhGCSF) on a canine spinal cord injury model after balloon compression at the first lumbar vertebra. Twenty-five adult mongrel dogs were assigned to five groups according to treatment after a spinal cord injury: no treatment (CN); saline treatment (CP); rmhGCSF treatment (G); UCB-MSCs treatment (UCB-MSC); co-treatment (UCBG). The UCBMSCs isolated from cord blood of canine fetuses were prepared as 10(6) cells/150 microl saline. The UCB-MSCs were directly injected into the injured site of the spinal cord and rmhGCSF was administered subcutaneously 1 week after the induction of spinal cord injury. The Olby score, magnetic resonance imaging, somatosensory evoked potentials and histopathological examinations were used to evaluate the functional recovery after transplantation. The Olby scores of all groups were zero at the 0-week evaluation. At 2 week after the transplantation, the Olby scores in the groups with the UCB-MSC and UCBG were significantly higher than in the CN and CP groups. However, there were no significant differences between the UCB-MSC and UCBG groups, and between the CN and CP groups. These comparisons remained stable at 4 and 8 week after transplantation. There was significant improvement in the nerve conduction velocity based on the somatosensory evoked potentials. In addition, a distinct structural consistency of the nerve cell bodies was noted in the lesion of the spinal cord of the UCB-MSC and UCBG groups. These results suggest that transplantation of the UCB-MSCs resulted in recovery of nerve function in dogs with a spinal cord injury and may be considered as a therapeutic modality for spinal cord injury.

Transplantation of canine umbilical cord blood-derived mesenchymal stem cells in experimentally induced spinal cord injured dogs

PubMed Central

Lim, Ji-Hey; Byeon, Ye-Eun; Ryu, Hak-Hyun; Jeong, Yun-Hyeok; Lee, Young-Won; Kim, Wan Hee

2007-01-01

This study was to determine the effects of allogenic umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) and recombinant methionyl human granulocyte colony-stimulating factor (rmhGCSF) on a canine spinal cord injury model after balloon compression at the first lumbar vertebra. Twenty-five adult mongrel dogs were assigned to five groups according to treatment after a spinal cord injury: no treatment (CN); saline treatment (CP); rmhGCSF treatment (G); UCB-MSCs treatment (UCB-MSC); co-treatment (UCBG). The UCB-MSCs isolated from cord blood of canine fetuses were prepared as 106 cells/150 µl saline. The UCB-MSCs were directly injected into the injured site of the spinal cord and rmhGCSF was administered subcutaneously 1 week after the induction of spinal cord injury. The Olby score, magnetic resonance imaging, somatosensory evoked potentials and histopathological examinations were used to evaluate the functional recovery after transplantation. The Olby scores of all groups were zero at the 0-week evaluation. At 2 week after the transplantation, the Olby scores in the groups with the UCB-MSC and UCBG were significantly higher than in the CN and CP groups. However, there were no significant differences between the UCB-MSC and UCBG groups, and between the CN and CP groups. These comparisons remained stable at 4 and 8 week after transplantation. There was significant improvement in the nerve conduction velocity based on the somatosensory evoked potentials. In addition, a distinct structural consistency of the nerve cell bodies was noted in the lesion of the spinal cord of the UCB-MSC and UCBG groups. These results suggest that transplantation of the UCB-MSCs resulted in recovery of nerve function in dogs with a spinal cord injury and may be considered as a therapeutic modality for spinal cord injury. PMID:17679775

Making sense out of spinal cord somatosensory development

PubMed Central

Seal, Rebecca P.

2016-01-01

The spinal cord integrates and relays somatosensory input, leading to complex motor responses. Research over the past couple of decades has identified transcription factor networks that function during development to define and instruct the generation of diverse neuronal populations within the spinal cord. A number of studies have now started to connect these developmentally defined populations with their roles in somatosensory circuits. Here, we review our current understanding of how neuronal diversity in the dorsal spinal cord is generated and we discuss the logic underlying how these neurons form the basis of somatosensory circuits. PMID:27702783

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.

Altered spinal cord activity during sexual stimulation in women with SCI: a pilot fMRI study.

PubMed

Alexander, Marcalee; Kozyrev, Natalie; Figley, Chase R; Richards, J Scott

2017-01-01

The objective of this study was to assess the feasibility of the use of functional magnetic resonance imaging (fMRI) to evaluate the spinal activation during sexual response of the thoracic, lumbar and sacral spinal cord. This is a laboratory-based pilot study in human females at a University-based medical center in the United States. In three healthy spinal cord injury (SCI) females, spinal cord activations during sexual audiovisual stimulation (alone), genital self-stimulation (alone) and simultaneous audiovisual and genital self-stimulation (combined) were assessed and then compared with each subjects' remaining sensory and motor function. Spinal fMRI responses of the intermediolateral columns were found during audiovisual stimulation in both subjects with incomplete injuries, but they were not observed in the subject with a complete injury. Moreover, sacral responses to combined stimulation differed greatly between the subjects with complete and incomplete injuries. These results not only provide the first in vivo documentation of spinal fMRI responses associated with sexual arousal in women with SCIs, but also suggest that spinal cord fMRI is capable of distinguishing between injury subtypes. Therefore, although there are certain limitations associated with fMRI during sexual stimulation (for example, movement artifacts, an artificially controlled environment and so), these findings demonstrate the potential utility of incorporating spinal cord fMRI in future research to evaluate the impact of specific patterns of SCI on sexual responses and/or the effects of treatment.

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

Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury.

PubMed

Keirstead, Hans S; Nistor, Gabriel; Bernal, Giovanna; Totoiu, Minodora; Cloutier, Frank; Sharp, Kelly; Steward, Oswald

2005-05-11

Demyelination contributes to loss of function after spinal cord injury, and thus a potential therapeutic strategy involves replacing myelin-forming cells. Here, we show that transplantation of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function. OPCs were injected 7 d or 10 months after injury. In both cases, transplanted cells survived, redistributed over short distances, and differentiated into oligodendrocytes. Animals that received OPCs 7 d after injury exhibited enhanced remyelination and substantially improved locomotor ability. In contrast, when OPCs were transplanted 10 months after injury, there was no enhanced remyelination or locomotor recovery. These studies document the feasibility of predifferentiating hESCs into functional OPCs and demonstrate their therapeutic potential at early time points after spinal cord injury.

Management of subaxial cervical facet dislocation through anterior approach monitored by spinal cord evoked potential.

PubMed

Du, Wei; Wang, Cheng; Tan, Jiangwei; Shen, Binghua; Ni, Shuqin; Zheng, Yanping

2014-01-01

Retrospective case series. To discuss the clinical efficacy of anterior cervical surgery of decompression, reduction, stabilization, and fusion in treating subaxial cervical facet dislocation without spinal cord injury or with mild spinal cord injury monitored by spinal cord evoked potential. The optimal treatment of lower cervical facet dislocation has been controversial. Because of the risk of iatrogenic damage of neurological function, it is challenging for surgeons to manage the lower cervical facet dislocation without or with mild spinal cord injury. To avoid the risks, more secure strategy need to be designed. A retrospective study was performed on 17 cases of subaxial cervical facet dislocation without spinal cord injury or with mild spinal cord injury treated by anterior cervical surgery under spinal cord evoked potential monitor from January 2008 to June 2012. There were 12 males, 5 females, with a mean age of 40.1 years (from 21 to 73 yr). Dislocation sites: 1 in C3-C4, 2 in C4-C5, 6 in C5-C6, 8 in C6-C7; 10 cases with unilateral cervical facet dislocation, 7 cases with bilateral dislocation. Thirteen patients were preoperatively classified as grade D and 4 as E according to Frankel standard. All patients were followed up for average of 16 months. All operations were completed successfully. Postoperative radiographs showed that the sequence and curvature of the cervical spine were well recovered. And, evidence of intervertebral fusion was observed at 3 months in all cases. No redislocation or symptoms of spinal cord injury occurred. Thirteen cases with mild spinal cord injury recovered at 1 month after operation. Anterior cervical surgery of decompression, reduction, stabilization, and fusion monitored by spinal cord evoked potential is an effective and safe method for treatment of subaxial cervical facet dislocation without or with mild spinal cord injury. 4.

Transplantation of human immature dental pulp stem cell in dogs with chronic spinal cord injury.

PubMed

Feitosa, Matheus Levi Tajra; Sarmento, Carlos Alberto Palmeira; Bocabello, Renato Zonzini; Beltrão-Braga, Patrícia Cristina Baleeiro; Pignatari, Graciela Conceição; Giglio, Robson Fortes; Miglino, Maria Angelica; Orlandin, Jéssica Rodrigues; Ambrósio, Carlos Eduardo

2017-07-01

To investigate the therapeutic potential of human immature dental pulp stem cells in the treatment of chronic spinal cord injury in dogs. Three dogs of different breeds with chronic SCI were presented as animal clinical cases. Human immature dental pulp stem cells were injected at three points into the spinal cord, and the animals were evaluated by limb function and magnetic resonance imaging (MRI) pre and post-operative. There was significant improvement from the limb function evaluated by Olby Scale, though it was not supported by the imaging data provided by MRI and clinical sign and evaluation. Human dental pulp stem cell therapy presents promising clinical results in dogs with chronic spinal cord injuries, if used in association with physical therapy.

The Effectiveness and Safety of Exoskeletons as Assistive and Rehabilitation Devices in the Treatment of Neurologic Gait Disorders in Patients with Spinal Cord Injury: A Systematic Review

PubMed Central

Fisahn, Christian; Aach, Mirko; Jansen, Oliver; Moisi, Marc; Mayadev, Angeli; Pagarigan, Krystle T.; Dettori, Joseph R.; Schildhauer, Thomas A.

2016-01-01

Study Design Systematic review. Clinical Questions (1) When used as an assistive device, do wearable exoskeletons improve lower extremity function or gait compared with knee-ankle-foot orthoses (KAFOs) in patients with complete or incomplete spinal cord injury? (2) When used as a rehabilitation device, do wearable exoskeletons improve lower extremity function or gait compared with other rehabilitation strategies in patients with complete or incomplete spinal cord injury? (3) When used as an assistive or rehabilitation device, are wearable exoskeletons safe compared with KAFO for assistance or other rehabilitation strategies for rehabilitation in patients with complete or incomplete spinal cord injury? Methods PubMed, Cochrane, and Embase databases and reference lists of key articles were searched from database inception to May 2, 2016, to identify studies evaluating the effectiveness of wearable exoskeletons used as assistive or rehabilitative devices in patients with incomplete or complete spinal cord injury. Results No comparison studies were found evaluating exoskeletons as an assistive device. Nine comparison studies (11 publications) evaluated the use of exoskeletons as a rehabilitative device. The 10-meter walk test velocity and Spinal Cord Independence Measure scores showed no difference in change from baseline among patients undergoing exoskeleton training compared with various comparator therapies. The remaining primary outcome measures of 6-minute walk test distance and Walking Index for Spinal Cord Injury I and II and Functional Independence Measure–Locomotor scores showed mixed results, with some studies indicating no difference in change from baseline between exoskeleton training and comparator therapies, some indicating benefit of exoskeleton over comparator therapies, and some indicating benefit of comparator therapies over exoskeleton. Conclusion There is no data to compare locomotion assistance with exoskeleton versus conventional KAFOs. There is no consistent benefit from rehabilitation using an exoskeleton versus a variety of conventional methods in patients with chronic spinal cord injury. Trials comparing later-generation exoskeletons are needed. PMID:27853668

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.

Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal Cord Injury

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-14-2-0132 TITLE: Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal Cord Injury...per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and...COVERED 29 Sep 2015 - 28 Sep 2016 4. TITLE AND SUBTITLE Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal

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

Potential of human dental stem cells in repairing the complete transection of rat spinal cord

NASA Astrophysics Data System (ADS)

Yang, Chao; Li, Xinghan; Sun, Liang; Guo, Weihua; Tian, Weidong

2017-04-01

Objective. The adult spinal cord of mammals contains a certain amount of neural precursor cells, but these endogenous cells have a limited capacity for replacement of lost cells after spinal cord injury. The exogenous stem cells transplantation has become a therapeutic strategy for spinal cord repairing because of their immunomodulatory and differentiation capacity. In addition, dental stem cells originating from the cranial neural crest might be candidate cell sources for neural engineering. Approach. Human dental follicle stem cells (DFSCs), stem cells from apical papilla (SCAPs) and dental pulp stem cells (DPSCs) were isolated and identified in vitro, then green GFP-labeled stem cells with pellets were transplanted into completely transected spinal cord. The functional recovery of rats and multiple neuro-regenerative mechanisms were explored. Main results. The dental stem cells, especially DFSCs, demonstrated the potential in repairing the completely transected spinal cord and promote functional recovery after injury. The major involved mechanisms were speculated below: First, dental stem cells inhibited the expression of interleukin-1β to reduce the inflammatory response; second, they inhibited the expression of ras homolog gene family member A (RhoA) to promote neurite regeneration; third, they inhibited the sulfonylurea receptor1 (SUR-1) expression to reduce progressive hemorrhagic necrosis; lastly, parts of the transplanted cells survived and differentiated into mature neurons and oligodendrocytes but not astrocyte, which is beneficial for promoting axons growth. Significance. Dental stem cells presented remarkable tissue regenerative capability after spinal cord injury through immunomodulatory, differentiation and protection capacity.

Effect of DSPE-PEG on compound action potential, injury potential and ion concentration following compression in ex vivo spinal cord.

PubMed

Wang, Aihua; Huo, Xiaolin; Zhang, Guanghao; Wang, Xiaochen; Zhang, Cheng; Wu, Changzhe; Rong, Wei; Xu, Jing; Song, Tao

2016-05-04

It has been shown that polyethylene glycol (PEG) can reseal membrane disruption on the spinal cord, but only high concentrations of PEG have been shown to have this effect. Therefore, the effect of PEG is somewhat limited, and it is necessary to investigate a new approach to repair spinal cord injury. This study assesses the ability of 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly (ethylene glycol)) 2000] (DSPE-PEG) to recover physiological function and attenuate the injury-induced influx of extracellular ions in ex vivo spinal cord injury. Isolated spinal cords were subjected to compression injury and treated with PEG or DSPE-PEG immediately after injury. The compound action potential (CAP) was recorded before and after injury to assess the functional recovery. Furthermore, injury potential, the difference in gap potentials before and after compression, and the concentration of intracellular ions were used to evaluate the effect of DSPE-PEG on reducing ion influx. Data showed that the injury potential and ion concentration of the untreated, PEG and DSPE-PEG group, without significant difference among them, are remarkably higher than those of the intact group. Moreover, the CAP recovery of the DSPE-PEG and PEG treated spinal cords was significantly greater than that of the untreated spinal cords. The level of CAP recovery in the DSPE-PEG and PEG treated groups was the same, but the concentration of DSPE-PEG used was much lower than the concentration of PEG. These results suggest that instant application of DSPE-PEG could effectively repair functional disturbance in SCI at a much lower concentration than PEG. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Early gene expression during natural spinal cord regeneration in the salamander Ambystoma mexicanum.

PubMed

Monaghan, James R; Walker, John A; Page, Robert B; Putta, Srikrishna; Beachy, Christopher K; Voss, S Randal

2007-04-01

In contrast to mammals, salamanders have a remarkable ability to regenerate their spinal cord and recover full movement and function after tail amputation. To identify genes that may be associated with this greater regenerative ability, we designed an oligonucleotide microarray and profiled early gene expression during natural spinal cord regeneration in Ambystoma mexicanum. We sampled tissue at five early time points after tail amputation and identified genes that registered significant changes in mRNA abundance during the first 7 days of regeneration. A list of 1036 statistically significant genes was identified. Additional statistical and fold change criteria were applied to identify a smaller list of 360 genes that were used to describe predominant expression patterns and gene functions. Our results show that a diverse injury response is activated in concert with extracellular matrix remodeling mechanisms during the early acute phase of natural spinal cord regeneration. We also report gene expression similarities and differences between our study and studies that have profiled gene expression after spinal cord injury in rat. Our study illustrates the utility of a salamander model for identifying genes and gene functions that may enhance regenerative ability in mammals.

Electronic bypass of spinal lesions: activation of lower motor neurons directly driven by cortical neural signals.

PubMed

Li, Yan; Alam, Monzurul; Guo, Shanshan; Ting, K H; He, Jufang

2014-07-03

Lower motor neurons in the spinal cord lose supraspinal inputs after complete spinal cord injury, leading to a loss of volitional control below the injury site. Extensive locomotor training with spinal cord stimulation can restore locomotion function after spinal cord injury in humans and animals. However, this locomotion is non-voluntary, meaning that subjects cannot control stimulation via their natural "intent". A recent study demonstrated an advanced system that triggers a stimulator using forelimb stepping electromyographic patterns to restore quadrupedal walking in rats with spinal cord transection. However, this indirect source of "intent" may mean that other non-stepping forelimb activities may false-trigger the spinal stimulator and thus produce unwanted hindlimb movements. We hypothesized that there are distinguishable neural activities in the primary motor cortex during treadmill walking, even after low-thoracic spinal transection in adult guinea pigs. We developed an electronic spinal bridge, called "Motolink", which detects these neural patterns and triggers a "spinal" stimulator for hindlimb movement. This hardware can be head-mounted or carried in a backpack. Neural data were processed in real-time and transmitted to a computer for analysis by an embedded processor. Off-line neural spike analysis was conducted to calculate and preset the spike threshold for "Motolink" hardware. We identified correlated activities of primary motor cortex neurons during treadmill walking of guinea pigs with spinal cord transection. These neural activities were used to predict the kinematic states of the animals. The appropriate selection of spike threshold value enabled the "Motolink" system to detect the neural "intent" of walking, which triggered electrical stimulation of the spinal cord and induced stepping-like hindlimb movements. We present a direct cortical "intent"-driven electronic spinal bridge to restore hindlimb locomotion after complete spinal cord injury.

NT3-chitosan enables de novo regeneration and functional recovery in monkeys after spinal cord injury.

PubMed

Rao, Jia-Sheng; Zhao, Can; Zhang, Aifeng; Duan, Hongmei; Hao, Peng; Wei, Rui-Han; Shang, Junkui; Zhao, Wen; Liu, Zuxiang; Yu, Juehua; Fan, Kevin S; Tian, Zhaolong; He, Qihua; Song, Wei; Yang, Zhaoyang; Sun, Yi Eve; Li, Xiaoguang

2018-06-12

Spinal cord injury (SCI) often leads to permanent loss of motor, sensory, and autonomic functions. We have previously shown that neurotrophin3 (NT3)-loaded chitosan biodegradable material allowed for prolonged slow release of NT3 for 14 weeks under physiological conditions. Here we report that NT3-loaded chitosan, when inserted into a 1-cm gap of hemisectioned and excised adult rhesus monkey thoracic spinal cord, elicited robust axonal regeneration. Labeling of cortical motor neurons indicated motor axons in the corticospinal tract not only entered the injury site within the biomaterial but also grew across the 1-cm-long lesion area and into the distal spinal cord. Through a combination of magnetic resonance diffusion tensor imaging, functional MRI, electrophysiology, and kinematics-based quantitative walking behavioral analyses, we demonstrated that NT3-chitosan enabled robust neural regeneration accompanied by motor and sensory functional recovery. Given that monkeys and humans share similar genetics and physiology, our method is likely translatable to human SCI repair.

International spinal cord injury pulmonary function basic data set.

PubMed

Biering-Sørensen, F; Krassioukov, A; Alexander, M S; Donovan, W; Karlsson, A-K; Mueller, G; Perkash, I; Sheel, A William; Wecht, J; Schilero, G J

2012-06-01

To develop the International Spinal Cord Injury (SCI) Pulmonary Function Basic Data Set within the framework of the International SCI Data Sets in order to facilitate consistent collection and reporting of basic bronchopulmonary findings in the SCI population. International. The SCI Pulmonary Function Data Set was developed by an international working group. The initial data set document was revised on the basis of suggestions from members of the Executive Committee of the International SCI Standards and Data Sets, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, American Spinal Injury Association (ASIA) Board, other interested organizations and societies and individual reviewers. In addition, the data set was posted for 2 months on ISCoS and ASIA websites for comments. The final International SCI Pulmonary Function Data Set contains questions on the pulmonary conditions diagnosed before spinal cord lesion,if available, to be obtained only once; smoking history; pulmonary complications and conditions after the spinal cord lesion, which may be collected at any time. These data include information on pneumonia, asthma, chronic obstructive pulmonary disease and sleep apnea. Current utilization of ventilator assistance including mechanical ventilation, diaphragmatic pacing, phrenic nerve stimulation and Bi-level positive airway pressure can be reported, as well as results from pulmonary function testing includes: forced vital capacity, forced expiratory volume in one second and peak expiratory flow. The complete instructions for data collection and the data sheet itself are freely available on the website of ISCoS (http://www.iscos.org.uk).

Sustained delivery of bioactive neurotrophin-3 to the injured spinal cord.

PubMed

Elliott Donaghue, Irja; Tator, Charles H; Shoichet, Molly S

2015-01-01

Spinal cord injury is a debilitating condition that currently lacks effective clinical treatment. Neurotrophin-3 (NT-3) has been demonstrated in experimental animal models to induce axonal regeneration and functional improvements, yet its local delivery remains challenging. For ultimate clinical translation, a drug delivery system is required for localized, sustained, and minimally invasive release. Here, an injectable composite drug delivery system (DDS) composed of biodegradable polymeric nanoparticles dispersed in a hyaluronan/methyl cellulose hydrogel was injected into the intrathecal space to achieve acute local delivery to the spinal cord after a thoracic clip compression injury. NT-3 was encapsulated in the DDS and released in vitro for up to 50 d. With a single injection of the DDS into the intrathecal space of the injured spinal cord, NT-3 diffused ventrally through the cord and was detectable in the spinal cord for at least 28 d therein. Delivery of NT-3 resulted in significant axon growth with no effect on the astroglial response to injury in comparison with vehicle and injury controls. NT-3 treatment promoted functional improvements at 21 d according to the Basso Beattie Bresnahan locomotor scale in comparison with the DDS alone. The sustained delivery of bioactive NT-3 to the injured spinal cord achieved in this study demonstrates the promise of this DDS for central nervous system repair.

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.

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.

More preoperative flexibility implies adequate neural pliability for curve correction without prophylactic untethering in scoliosis patients with asymptomatic tethered spinal cord, a retrospective study.

PubMed

Zhou, Zhenhai; Zhang, Hongqi; Guo, Chaofeng; Yu, Honggui; Wang, Longjie; Guo, Qiang

2017-06-15

Tethered spinal cord is frequently associated with scoliosis. It is still controversial whether a prophylactic untethering is necessary before correction procedure in scoliosis patients with tethered spinal cord. In this study we determined the clinical outcome of a one-stage posterior scoliosis correction without a prophylactic untethering for treating scoliosis with an asymptomatic tethered spinal cord. Seventeen (5 males and 12 females) scoliosis patients with tethered spinal cords were retrospectively reviewed. All patients underwent a one-stage posterior scoliosis correction without preventive untethering. Parameters of radiograph were used to assess correction result. The Scoliosis Research Society (SRS)-22 questionnaire was analyzed pre- and post-operatively to evaluate the clinical outcomes. The modified Japanese Orthopaedic Association (mJOA) score was used to assess the pre- and post-operative spinal cord function. The post-operative coronal Cobb angle was significantly decreased compared with preoperative. (23.8 ± 6.4° vs. 58.4 ± 12.6°, P < 0.01). The coronal Cobb angle was 22.4 ± 6.8° at the final follow-up evaluation. The apical vertebral translation (AVT) was also decreased significantly. (27.5 mm vs. 60.9 mm, P < 0.01). The SRS-22 total score was improved at the 1-year follow-up evaluation compared with the pre-operative SRS-22 total score (87 ± 4 vs. 70 ± 5, p < 0.05). The functional activities, pain, self-image, mental health, and surgery satisfactory scores at the final follow-up evaluation were all improved compared with the corresponding pre-operative scores, especially the self-image and mental health scores (p < 0.05). The spinal cord function was stable and there was no new neurological symptoms after scoliosis correction. No difference existed between the pre- and post-operative total mJOA score (26 ± 2 vs. 27 ± 2, p = 0.39), which including subjective symptom (p = 0.07), clinical symptom (p = 0.33), daily activities (p = 0.44) and bladder function (p = 0.67). One-stage posterior scoliosis correction is a safe and effective surgical procedure for scoliosis patients combined with asymptomatic tethered spinal cord who have adequate spinal cord function reserve.

Nestin- and Doublecortin-Positive Cells Reside in Adult Spinal Cord Meninges and Participate in Injury-Induced Parenchymal Reaction

PubMed Central

Decimo, Ilaria; Bifari, Francesco; Rodriguez, Francisco Javier; Malpeli, Giorgio; Dolci, Sissi; Lavarini, Valentina; Pretto, Silvia; Vasquez, Sandra; Sciancalepore, Marina; Montalbano, Alberto; Berton, Valeria; Krampera, Mauro; Fumagalli, Guido

2011-01-01

Adult spinal cord has little regenerative potential, thus limiting patient recovery following injury. In this study, we describe a new population of cells resident in the adult rat spinal cord meninges that express the neural stem/precursor markers nestin and doublecortin. Furthermore, from dissociated meningeal tissue a neural stem cell population was cultured in vitro and subsequently shown to differentiate into functional neurons or mature oligodendrocytes. Proliferation rate and number of nestin- and doublecortin-positive cells increased in vivo in meninges following spinal cord injury. By using a lentivirus-labeling approach, we show that meningeal cells, including nestin- and doublecortin-positive cells, migrate in the spinal cord parenchyma and contribute to the glial scar formation. Our data emphasize the multiple roles of meninges in the reaction of the parenchyma to trauma and indicate for the first time that spinal cord meninges are potential niches harboring stem/precursor cells that can be activated by injury. Meninges may be considered as a new source of adult stem/precursor cells to be further tested for use in regenerative medicine applied to neurological disorders, including repair from spinal cord injury. Stem Cells 2011;29:2062–2076. PMID:22038821

Nestin- and doublecortin-positive cells reside in adult spinal cord meninges and participate in injury-induced parenchymal reaction.

PubMed

Decimo, Ilaria; Bifari, Francesco; Rodriguez, Francisco Javier; Malpeli, Giorgio; Dolci, Sissi; Lavarini, Valentina; Pretto, Silvia; Vasquez, Sandra; Sciancalepore, Marina; Montalbano, Alberto; Berton, Valeria; Krampera, Mauro; Fumagalli, Guido

2011-12-01

Adult spinal cord has little regenerative potential, thus limiting patient recovery following injury. In this study, we describe a new population of cells resident in the adult rat spinal cord meninges that express the neural stem/precursor markers nestin and doublecortin. Furthermore, from dissociated meningeal tissue a neural stem cell population was cultured in vitro and subsequently shown to differentiate into functional neurons or mature oligodendrocytes. Proliferation rate and number of nestin- and doublecortin-positive cells increased in vivo in meninges following spinal cord injury. By using a lentivirus-labeling approach, we show that meningeal cells, including nestin- and doublecortin-positive cells, migrate in the spinal cord parenchyma and contribute to the glial scar formation. Our data emphasize the multiple roles of meninges in the reaction of the parenchyma to trauma and indicate for the first time that spinal cord meninges are potential niches harboring stem/precursor cells that can be activated by injury. Meninges may be considered as a new source of adult stem/precursor cells to be further tested for use in regenerative medicine applied to neurological disorders, including repair from spinal cord injury. Copyright © 2011 AlphaMed Press.

NORADRENERGIC INNERVATION OF THE RAT SPINAL CORD CAUDAL TO A COMPLETE SPINAL CORD TRANSECTION: EFFECTS OF OLFACTORY ENSHEATHING GLIA

PubMed Central

Takeoka, Aya; Kubasak, Marc D.; Zhong, Hui; Kaplan, Jennifer; Roy, Roland R.; Phelps, Patricia E.

2010-01-01

Transplantation of olfactory bulb-derived olfactory ensheathing glia (OEG) combined with step training improves hindlimb locomotion in adult rats with a complete spinal cord transection. Spinal cord injury studies use the presence of noradrenergic (NA) axons caudal to the injury site as evidence of axonal regeneration and we previously found more NA axons just caudal to the transection in OEG- than media-injected spinal rats. We therefore hypothesized that OEG transplantation promotes descending coeruleospinal regeneration that contributes to the recovery of hindlimb locomotion. Now we report that NA axons are present throughout the caudal stump of both media- and OEG-injected spinal rats and they enter the spinal cord from the periphery via dorsal and ventral roots and along large penetrating blood vessels. These results indicate that the presence of NA fibers in the caudal spinal cord is not a reliable indicator of coeruleospinal regeneration. We then asked if NA axons appose cholinergic neurons associated with motor functions, i.e., central canal cluster and partition cells (active during fictive locomotion) and somatic motor neurons (SMNs). We found more NA varicosities adjacent to central canal cluster cells, partition cells, and SMNs in the lumbar enlargement of OEG- than media-injected rats. As non-synaptic release of NA is common in the spinal cord, more associations between NA varicosities and motor-associated cholinergic neurons in the lumbar spinal cord may contribute to the improved treadmill stepping observed in OEG-injected spinal rats. This effect could be mediated through direct association with SMNs and/or indirectly via cholinergic interneurons. PMID:20025875

SU-F-T-113: Inherent Functional Dependence of Spinal Cord Doses of Variable Irradiated Volumes in Spine SBRT

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

Ma, L; Braunstein, S; Chiu, J

2016-06-15

Purpose: Spinal cord tolerance for SBRT has been recommended for the maximum point dose level or at irradiated volumes such as 0.35 mL or 10% of contoured volumes. In this study, we investigated an inherent functional relationship that associates these dose surrogates for irradiated spinal cord volumes of up to 3.0 mL. Methods: A hidden variable termed as Effective Dose Radius (EDR) was formulated based on a dose fall-off model to correlate dose at irradiated spinal cord volumes ranging from 0 mL (point maximum) to 3.0 mL. A cohort of 15 spine SBRT cases was randomly selected to derive anmore » EDR-parameterized formula. The mean prescription dose for the studied cases was 21.0±8.0 Gy (range, 10–40Gy) delivered in 3±1 fractions with target volumes of 39.1 ± 70.6 mL. Linear regression and variance analysis were performed for the fitting parameters of variable EDR values. Results: No direct correlation was found between the dose at maximum point and doses at variable spinal cord volumes. For example, Pearson R{sup 2} = 0.643 and R{sup 2}= 0.491 were obtained when correlating the point maximum dose with the spinal cord dose at 1 mL and 3 mL, respectively. However, near perfect correlation (R{sup 2} ≥0.99) was obtained when corresponding parameterized EDRs. Specifically, Pearson R{sup 2}= 0.996 and R{sup 2} = 0.990 were obtained when correlating EDR (maximum point dose) with EDR (dose at 1 mL) and EDR(dose at 3 mL), respectively. As a result, high confidence level look-up tables were established to correlate spinal cord doses at the maximum point to any finite irradiated volumes. Conclusion: An inherent functional relationship was demonstrated for spine SBRT. Such a relationship unifies dose surrogates at variable cord volumes and proves that a single dose surrogate (e.g. point maximum dose) is mathematically sufficient in constraining the overall spinal cord dose tolerance for SBRT.« less

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.

Neuromodulation of the neural circuits controlling the lower urinary tract.

PubMed

Gad, Parag N; Roy, Roland R; Zhong, Hui; Gerasimenko, Yury P; Taccola, Giuliano; Edgerton, V Reggie

2016-11-01

The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Herein we demonstrate that electrically evoked potentials in the hindlimb muscles and external urethral sphincter are modulated uniquely when the rat is stepping bipedally and not voiding, immediately pre-voiding, or when voiding. We also show that spinal cord stimulation can effectively neuromodulate the lower urinary tract via frequency-dependent stimulation patterns and that neural peripheral nerve stimulation can activate the external urethral sphincter both directly and via relays in the spinal cord. The data demonstrate that the sensorimotor networks controlling bladder and locomotion are highly integrated neurophysiologically and behaviorally and demonstrate how these two functions are modulated by sensory input from the tibial and pudental nerves. A more detailed understanding of the high level of interaction between these networks could lead to the integration of multiple neurophysiological strategies to improve bladder function. These data suggest that the development of strategies to improve bladder function should simultaneously engage these highly integrated networks in an activity-dependent manner. Copyright © 2016. Published by Elsevier Inc.

A cellular spinal cord scaffold seeded with rat adipose-derived stem cells facilitates functional recovery via enhancing axon regeneration in spinal cord injured rats

PubMed Central

Yin, Hong; Jiang, Tao; Deng, Xi; Yu, Miao; Xing, Hui; Ren, Xianjun

2018-01-01

Spinal cord injury (SCI), usually resulting in severe sensory and motor deficits, is a major public health concern. Adipose-derived stem cells (ADSCs), one type of adult stem cell, are free from ethical restriction, easily isolated and enriched. Therefore, ADSCs may provide a feasible cell source for cell-based therapies in treatment of SCI. The present study successfully isolated rat ADSCs (rADSCs) from Sprague-Dawley male rats and co-cultured them with acellular spinal cord scaffolds (ASCs). Then, a rat spinal cord hemisection model was built and rats were randomly divided into 3 groups: SCI only, ASC only, and ASC + ADSCs. Furthermore, behavioral tests were conducted to evaluate functional recovery. Hematoxylin & Eosin staining and immunofluorence were carried out to assess histopathological remodeling. In addition, biotinylated dextran amines anterograde tracing was employed to visualize axon regeneration. The data demonstrated that harvested cells, which were positive for cell surface antigen cluster of differentiation (CD) 29, CD44 and CD90 and negative for CD4, detected by flow cytometry analysis, held the potential to differentiate into osteocytes and adipocytes. Rats that received transplantation of ASCs seeded with rADSCs benefited greatly in functional recovery through facilitation of histopathological rehabilitation, axon regeneration and reduction of reactive gliosis. rADSCs co-cultured with ASCs may survive and integrate into the host spinal cord on day 14 post-SCI. PMID:29257299

Clinical Response of 277 Patients with Spinal Cord Injury to Stem Cell Therapy in Iraq

PubMed Central

Hammadi, Abdulmajeed Alwan; Marino, Andolina; Farhan, Saad

2012-01-01

Background and Objectives: Spinal cord injury is a common neurological problem secondary to car accidents, war injuries and other causes, it may lead to varying degrees of neurological disablement, and apart from physiotherapy there is no available treatment to regain neurological function loss. Our aim is to find a new method using autologous hematopoietic stem cells to gain some of the neurologic functions lost after spinal cord injury. Methods and Results: 277 patients suffering from spinal cord injury were submitted to an intrathecally treatment with peripheral stem cells. The cells were harvested from the peripheral blood after a treatment with G-CSF and then concentrated to 4∼ 6 ml. 43% of the patients improved; ASIA score shifted from A to B in 88 and from A to C in 32. The best results were achieved in patients treated within one year from the injury. Conclusions: Since mesenchymal cells increase in the peripheral blood after G-CSF stimulation, a peripheral blood harvest seems easier and cheaper than mesenchymal cell cultivation prior to injection. It seems reasonable treatment for spinal cord injury. PMID:24298358

Opioid administration following spinal cord injury: Implications for pain and locomotor recovery

PubMed Central

Woller, Sarah A.; Hook, Michelle A.

2013-01-01

Approximately one-third of people with a spinal cord injury (SCI) will experience persistent neuropathic pain following injury. This pain negatively affects quality of life and is difficult to treat. Opioids are among the most effective drug treatments, and are commonly prescribed, but experimental evidence suggests that opioid treatment in the acute phase of injury can attenuate recovery of locomotor function. In fact, spinal cord injury and opioid administration share several common features (e.g. central sensitization, excitotoxicity, aberrant glial activation) that have been linked to impaired recovery of function, as well as the development of pain. Despite these effects, the interactions between opioid use and spinal cord injury have not been fully explored. A review of the literature, described here, suggests that caution is warranted when administering opioids after SCI. Opioid administration may synergistically contribute to the pathology of SCI to increase the development of pain, decrease locomotor recovery, and leave individuals at risk for infection. Considering these negative implications, it is important that guidelines are established for the use of opioids following spinal cord and other central nervous system injuries. PMID:23501709

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.

Use of quadrupedal step training to re-engage spinal interneuronal networks and improve locomotor function after spinal cord injury.

PubMed

Shah, Prithvi K; Garcia-Alias, Guillermo; Choe, Jaehoon; Gad, Parag; Gerasimenko, Yury; Tillakaratne, Niranjala; Zhong, Hui; Roy, Roland R; Edgerton, V Reggie

2013-11-01

Can lower limb motor function be improved after a spinal cord lesion by re-engaging functional activity of the upper limbs? We addressed this issue by training the forelimbs in conjunction with the hindlimbs after a thoracic spinal cord hemisection in adult rats. The spinal circuitries were more excitable, and behavioural and electrophysiological analyses showed improved hindlimb function when the forelimbs were engaged simultaneously with the hindlimbs during treadmill step-training as opposed to training only the hindlimbs. Neuronal retrograde labelling demonstrated a greater number of propriospinal labelled neurons above and below the thoracic lesion site in quadrupedally versus bipedally trained rats. The results provide strong evidence that actively engaging the forelimbs improves hindlimb function and that one likely mechanism underlying these effects is the reorganization and re-engagement of rostrocaudal spinal interneuronal networks. For the first time, we provide evidence that the spinal interneuronal networks linking the forelimbs and hindlimbs are amenable to a rehabilitation training paradigm. Identification of this phenomenon provides a strong rationale for proceeding toward preclinical studies for determining whether training paradigms involving upper arm training in concert with lower extremity training can enhance locomotor recovery after neurological damage.

Therapeutic intraspinal stimulation to generate activity and promote long-term recovery.

PubMed

Mondello, Sarah E; Kasten, Michael R; Horner, Philip J; Moritz, Chet T

2014-01-01

Neuroprosthetic approaches have tremendous potential for the treatment of injuries to the brain and spinal cord by inducing appropriate neural activity in otherwise disordered circuits. Substantial work has demonstrated that stimulation applied to both the central and peripheral nervous system leads to immediate and in some cases sustained benefits after injury. Here we focus on cervical intraspinal microstimulation (ISMS) as a promising method of activating the spinal cord distal to an injury site, either to directly produce movements or more intriguingly to improve subsequent volitional control of the paretic extremities. Incomplete injuries to the spinal cord are the most commonly observed in human patients, and these injuries spare neural tissue bypassing the lesion that could be influenced by neural devices to promote recovery of function. In fact, recent results have demonstrated that therapeutic ISMS leads to modest but sustained improvements in forelimb function after an incomplete spinal cord injury (SCI). This therapeutic spinal stimulation may promote long-term recovery of function by providing the necessary electrical activity needed for neuron survival, axon growth, and synaptic stability.

The development of spinal cord anatomy.

PubMed

Pearce, J M S

2008-01-01

A panel illustrating spinal cord injury in The Dying Lioness in the British Museum dates to 650 BC. This paper outlines the subsequent progression of knowledge of the anatomy of the spinal cord. The animal dissections of Galen are considered because his deductions persisted through the Dark Ages until the late 18th century. Anatomy advanced gradually to yield discoveries of the complex tracts and grey matter elements of the cord and their functions. Amongst many distinguished exponents, the works of Blasius, Huber, Vicq d'Azyr and Stilling are emphasised. (c) 2008 S. Karger AG, Basel

Sexual counseling with spinal cord-injured clients.

PubMed

Miller, D K

1975-01-01

Spinal cord-injured clients have many fears and misapprehension about their sexual functioning. Common beliefs include: (a) disabled men cannot sexually satisfy able-bodied women; and (b) cord-injured persons cannot have sexual intercourse. Such misapprehensions can be helped by the counselor's willingness to discuss sexual issues openly. Clients need a clear and accurate picture of the facts, as well as encouragement and support to help them rediscover their sexuality. Spinal cord injury does not mean sexual incapacity. Given a knowing and patient partner, most clients can enjoy a satisfying sex life.

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

Can the mammalian lumbar spinal cord learn a motor task?

PubMed

Hodgson, J A; Roy, R R; de Leon, R; Dobkin, B; Edgerton, V R

1994-12-01

Progress toward restoring locomotor function in low thoracic spinal transected cats and the application of similar techniques to patients with spinal cord injury is reviewed. Complete spinal cord transection (T12-T13) in adult cats results in an immediate loss of locomotor function in the hindlimbs. Limited locomotor function returns after several months in cats that have not received specific therapies designed to restore hindlimb stepping. Training transected cats to step on a treadmill for 30 min.d-1 and 5 d.wk-1 greatly improves their stepping ability. The most successful outcome was in cats where training began early, i.e., 1 wk after spinal transection. Cats trained to stand instead of stepping had great difficulty using the hindlimbs for locomotion. These effects were reversible over a 20-month period such that cats unable to step as a result of standing training could be trained to step and, conversely, locomotion in stepping-trained cats could be abolished by standing training. These results indicate that the spinal cord is capable of learning specific motor tasks. It has not been possible to elicit locomotion in patients with clinically complete spinal injuries, but appropriately coordinated EMG activity has been demonstrated in musculature of the legs during assisted locomotion on a treadmill.

Brain and cord myelin water imaging: a progressive multiple sclerosis biomarker

PubMed Central

Kolind, Shannon; Seddigh, Arshia; Combes, Anna; Russell-Schulz, Bretta; Tam, Roger; Yogendrakumar, Vignan; Deoni, Sean; Sibtain, Naomi A.; Traboulsee, Anthony; Williams, Steven C.R.; Barker, Gareth J.; Brex, Peter A.

2015-01-01

Objectives Conventional magnetic resonance imaging (MRI) is used to diagnose and monitor inflammatory disease in relapsing remitting (RR) multiple sclerosis (MS). In the less common primary progressive (PP) form of MS, in which focal inflammation is less evident, biomarkers are still needed to enable evaluation of novel therapies in clinical trials. Our objective was to characterize the association — across the brain and cervical spinal cord — between clinical disability measures in PPMS and two potential biomarkers (one for myelin, and one for atrophy, both resulting from the same imaging technique). Methods Multi-component driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) MRI of the brain and cervical spinal cord were obtained for 15 PPMS patients and 11 matched controls. Data were analysed to estimate the signal related to myelin water (VFM), as well as volume measurements. MS disability was assessed using the Multiple Sclerosis Functional Composite score, which includes measures of cognitive processing (Paced Auditory Serial Addition Test), manual dexterity (9-Hole Peg Test) and ambulatory function (Timed 25-Foot Walk); and the Expanded Disability Status Scale. Results Brain and spinal cord volumes were different in PPMS compared to controls, particularly ventricular (+ 46%, p = 0.0006) and cervical spinal cord volume (− 16%, p = 0.0001). Brain and spinal cord myelin (VFM) were also reduced in PPMS (brain: − 11%, p = 0.01; spine: − 19%, p = 0.000004). Cognitive processing correlated with brain ventricular volume (p = 0.009). Manual dexterity correlated with brain ventricular volume (p = 0.007), and both brain and spinal cord VFM (p = 0.01 and 0.06, respectively). Ambulation correlated with spinal cord volume (p = 0.04) and spinal cord VFM (p = 0.04). Interpretation In this study we demonstrated that mcDESPOT can be used to measure myelin and atrophy in the brain and spinal cord. Results correlate well with clinical disability scores in PPMS representing cognitive, fine motor and ambulatory disability. PMID:26594633

Partial cure achieved in a patient with near-complete cervical spinal cord injury (95% injury) after 3 years of coordination dynamics therapy.

PubMed

Schalow, G

2009-01-01

This report describes a case of a now 20-year-old young lady with a severe spinal cord injury (SCI) at cervical 5/6 levels (ASIA A), in whom a repair of some spinal cord functions could be achieved within 3 years of optimal coordination dynamics therapy (CDT). Magnetic Resonance Imaging (MRI) showed a destruction of almost 95% of the cross-sectional area at the injury levels. The 5% (if at all) spared cord tissue most likely consisted of only sensory tracts, since no motor functions were preserved below the level of injury. A near-complete recovery of the important vegetative functions urinary bladder control, respiration, and vasomotor tone could be achieved. Her motor and sensory functions also improved to some extent, and she is off all medications. However, her motor recovery was limited and she is still wheel-chair-dependent. There is functional and structural (MRI) evidence that the human spinal cord regenerates upon CDT. The movement-based learning therapy included the training of supported crawling, up-righting, walking, running, jumping, balance training, and exercising on special CDT devices. The regeneration of the spinal cord started after more than one year of CDT, it was very limited but continuous, and gave rise to substantial functional recovery. The recovery induced by regeneration upon CDT was quantified in terms of transient increases of coordination dynamics values, the improvement of motor programs as assessed by surface electromyography (sEMG), the improvement of movement performances, and the increase of the spinal cord matter at the injury site, quantified by MRI. The similarity between the improvement at cellular and integrative (network) level during this regeneration and development is analyzed with respect to 'walking'. Comparing the effort, required to achieve substantial improvement in this case of severe cervical SCI (with 95% cord destruction; 5% spared tissue) with the effort required in the case of partial cervical SCI (50% destruction; 50% spared tissue), IT is noted that the 95% injury is 10 times more intractable. It is inferred that in severe SCI, the repair crucially depends on the percentage of the spared tissue (tracts fibres and neuronal networks) at the injury site. Improper handling of the patient therefore, as false transport or too late relief of spinal cord compression, may give rise to further mechanical damage of the cord tissue for which a later administered intensive cCDT cannot compensate for.

Plasticity in reflex pathways to the lower urinary tract following spinal cord injury

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2013-01-01

The lower urinary tract has two main functions, storage and periodic expulsion of urine, that are regulated by a complex neural control system in the brain and lumbosacral spinal cord. This neural system coordinates the activity of two functional units in the lower urinary tract: (1) a reservoir (the urinary bladder) and (2) an outlet (consisting of bladder neck, urethra and striated muscles of the external urethra sphincter). During urine storage the outlet is closed and the bladder is quiescent to maintain a low intravesical pressure. During micturition the outlet relaxes and the bladder contracts to promote efficient release of urine. This reciprocal relationship between bladder and outlet is generated by reflex circuits some of which are under voluntary control. Experimental studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through a coordination center (the pontine micturition center) located in the rostral brainstem. This reflex pathway is in turn modulated by higher centers in the cerebral cortex that are involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary control of voiding as well as the normal reflex pathways that coordinate bladder and sphincter function. Following spinal cord injury the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. However the bladder does not empty efficiently because coordination between the bladder and urethral outlet is lost. Studies in animals indicate that dysfunction of the lower urinary tract after spinal cord injury is dependent in part on plasticity of bladder afferent pathways as well as reorganization of synaptic connections in the spinal cord. Reflex plasticity is associated with changes in the properties of ion channels and electrical excitability of afferent neurons and appears to be mediated in part by neurotrophic factors released in the spinal cord and/or the peripheral target organs. PMID:21596038

Spontaneous recovery of locomotion induced by remaining fibers after spinal cord transection in adult rats.

PubMed

You, Si-Wei; Chen, Bing-Yao; Liu, Hui-Ling; Lang, Bing; Xia, Jie-Lai; Jiao, Xi-Ying; Ju, Gong

2003-01-01

A major issue in analysis of experimental results after spinal cord injury is spontaneous functional recovery induced by remaining nerve fibers. The authors investigated the relationship between the degree of locomotor recovery and the percentage and location of the fibers that spared spinal cord transection. The spinal cords of 12 adult rats were transected at T9 with a razor blade, which often resulted in sparing of nerve fibers in the ventral spinal cord. The incompletely-transected animals were used to study the degree of spontaneous recovery of hindlimb locomotion, evaluated with the BBB rating scale, in correlation to the extent and location of the remaining fibers. Incomplete transection was found in the ventral spinal cord in 42% of the animals. The degree of locomotor recovery was highly correlated with the percentage of the remaining fibers in the ventral and ventrolateral funiculi. In one of the rats, 4.82% of remaining fibers in unilateral ventrolateral funiculus were able to sustain a certain recovery of locomotion. Less than 5% of remaining ventrolateral white matter is sufficient for an unequivocal motor recovery after incomplete spinal cord injury. Therefore, for studies with spinal cord transection, the completeness of sectioning should be carefully checked before any conclusion can be reached. The fact that the degree of locomotor recovery is correlated with the percentage of remaining fibers in the ventrolateral spinal cord, exclusive of most of the descending motor tracts, may imply an essential role of propriospinal connections in the initiation of spontaneous locomotor recovery.

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.

Ethyl pyruvate attenuates spinal cord ischemic injury with a wide therapeutic window through inhibiting high-mobility group box 1 release in rabbits.

PubMed

Wang, Qiang; Ding, Qian; Zhou, Yiming; Gou, Xingchun; Hou, Lichao; Chen, Shaoyang; Zhu, Zhenghua; Xiong, Lize

2009-06-01

Ethyl pyruvate (EP) has been reported to offer a protective effect against ischemic injury through its antiinflammatory action. The nuclear protein high-mobility group box 1 (HMGB1) can activate inflammatory pathways when released from ischemic cells. This study was designed to investigate the neuroprotective effect of EP against spinal cord ischemic injury and the potential role of HMGB1 in this process. EP was administered at various time points before or after 20 min of spinal cord ischemia in male New Zealand rabbits. All animals were sacrificed at 72 h after reperfusion with modified Tarlov criteria, and the spinal cord segment (L4) was harvested for histopathological examination and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining. The HMGB1 levels in serum and spinal cord tissue were analyzed by enzyme-linked immunosorbent assay. The treatment of EP at 30 min before ischemia or at 6 h after reperfusion significantly improved the hind-limb motor function scores and increased the numbers of normal motor neurons, which was accompanied with reduction of the number of apoptotic neurons and levels of HMGB1 in serum and spinal cord tissue. The HMGB1 contents of spinal cord tissue correlated well with the numbers of apoptotic motor neurons in the anterior spinal cord at 72 h after reperfusion. These results suggest that EP affords a strong protection against the transient spinal cord ischemic injury with a wide therapeutic window through inhibition of HMGB1 release.

Spinal cord blood flow and ischemic injury after experimental sacrifice of thoracic and abdominal segmental arteries.

PubMed

Etz, Christian D; Homann, Tobias M; Luehr, Maximilian; Kari, Fabian A; Weisz, Donald J; Kleinman, George; Plestis, Konstadinos A; Griepp, Randall B

2008-06-01

Spinal cord blood flow (SCBF) after sacrifice of thoracoabdominal aortic segmental arteries (TAASA) during thoracoabdominal aortic aneurysm (TAAA) repair remains poorly understood. This study explored SCBF for 72 h after sacrifice of all TAASA. Fourteen juvenile Yorkshire pigs underwent complete serial TAASA sacrifice (T4-L5). Six control pigs underwent anesthesia and cooling to 32 degrees C with no TAASA sacrifice. In the experimental animals, spinal cord function was continuously monitored using motor evoked potentials (MEPs) until 1h after clamping the last TAASA. Fluorescent microspheres enabled segmental measurement of SCBF along the entire spinal cord before, and 5 min, 1 h, 5 h, 24 h and 72 h after complete TAASA sacrifice. A modified Tarlov score was obtained for 3 days after surgery. All the pigs with complete TAASA sacrifice retained normal cord function (MEP) until 1h after TAASA ligation. Seven pigs (50%) with complete TAASA sacrifice recovered after 72 h; seven pigs suffered paraparesis or paraplegia. Intraoperatively, and until 1h postoperatively, SCBF was similar among the three groups along the entire cord. Postoperatively, SCBF did not decrease in any group, but significant hyperemia occurred at 5h in controls and recovery animals, but did not occur in pigs that developed paraparesis or paraplegia in the T8-L2 segments (p=0.0002) and L3-S segments (p=0.0007). At 24h, SCBF remained marginally lower from T8 caudally; at 72h, SCBF was similar among all groups along the entire cord. SCBF in the segments T8-L2 at 5h predicted functional recovery (p=0.003). This study suggests that critical spinal cord ischemia after complete TAASA sacrifice does not occur immediately (intraoperatively), but is delayed 1-5h or longer after clamping, and represents failure to mount a hyperemic response to rewarming and awakening. The short duration of low SCBF associated with spinal cord injury suggests that hemodynamic and metabolic manipulation lasting only 24-72 h may allow routine preservation of normal cord function despite sacrifice of all TAASA secondary to surgical or endovascular repair of large TAAA.

Electrical stimulation and motor recovery.

PubMed

Young, Wise

2015-01-01

In recent years, several investigators have successfully regenerated axons in animal spinal cords without locomotor recovery. One explanation is that the animals were not trained to use the regenerated connections. Intensive locomotor training improves walking recovery after spinal cord injury (SCI) in people, and >90% of people with incomplete SCI recover walking with training. Although the optimal timing, duration, intensity, and type of locomotor training are still controversial, many investigators have reported beneficial effects of training on locomotor function. The mechanisms by which training improves recovery are not clear, but an attractive theory is available. In 1949, Donald Hebb proposed a famous rule that has been paraphrased as "neurons that fire together, wire together." This rule provided a theoretical basis for a widely accepted theory that homosynaptic and heterosynaptic activity facilitate synaptic formation and consolidation. In addition, the lumbar spinal cord has a locomotor center, called the central pattern generator (CPG), which can be activated nonspecifically with electrical stimulation or neurotransmitters to produce walking. The CPG is an obvious target to reconnect after SCI. Stimulating motor cortex, spinal cord, or peripheral nerves can modulate lumbar spinal cord excitability. Motor cortex stimulation causes long-term changes in spinal reflexes and synapses, increases sprouting of the corticospinal tract, and restores skilled forelimb function in rats. Long used to treat chronic pain, motor cortex stimuli modify lumbar spinal network excitability and improve lower extremity motor scores in humans. Similarly, epidural spinal cord stimulation has long been used to treat pain and spasticity. Subthreshold epidural stimulation reduces the threshold for locomotor activity. In 2011, Harkema et al. reported lumbosacral epidural stimulation restores motor control in chronic motor complete patients. Peripheral nerve or functional electrical stimulation (FES) has long been used to activate sacral nerves to treat bladder and pelvic dysfunction and to augment motor function. In theory, FES should facilitate synaptic formation and motor recovery after regenerative therapies. Upcoming clinical trials provide unique opportunities to test the theory.

Tonic and Rhythmic Spinal Activity Underlying Locomotion.

PubMed

Ivanenko, Yury P; Gurfinkel, Victor S; Selionov, Victor A; Solopova, Irina A; Sylos-Labini, Francesca; Guertin, Pierre A; Lacquaniti, Francesco

2017-05-12

In recent years, many researches put significant efforts into understanding and assessing the functional state of the spinal locomotor circuits in humans. Various techniques have been developed to stimulate the spinal cord circuitries, which may include both diffuse and quite specific tuning effects. Overall, the findings indicate that tonic and rhythmic spinal activity control are not separate phenomena but are closely integrated to properly initiate and sustain stepping. The spinal cord does not simply transmit information to and from the brain. Its physiologic state determines reflex, postural and locomotor control and, therefore, may affect the recovery of the locomotor function in individuals with spinal cord and brain injuries. This review summarizes studies that examine the rhythmogenesis capacity of cervical and lumbosacral neuronal circuitries in humans and its importance in developing central pattern generator-modulating therapies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effect of lycopene on the blood-spinal cord barrier after spinal cord injury in mice.

PubMed

Zhang, Qian; Wang, Jianbo; Gu, Zhengsong; Zhang, Qing; Zheng, Hong

2016-09-05

The current study aimed to investigate the effect of lycopene on the blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) in a mouse model. Lycopene inhibited lipid peroxidation and oxidative DNA damage as a highly efficient antioxidant and free radical scavenger. Lycopene (4 mg/kg/d) was administrated immediately following SCI. The permeability of the BSCB and water content in the spinal cord tissue were evaluated. Additionally, levels of expression of tight junction proteins and heme oxygenase-1 (HO-1) were determined with Western blotting. An enzyme-linked immunosorbent assay analysis of spinal cord tissue homogenates was performed 48 h after SCI to evaluate the expression of inflammation-related cytokines. In addition, recovery of motor function was assessed 1 d, 2 d, 5 d, 10 d, and 15 d after SCI using the Basso Mouse Scale to score locomotion. Compared to the group with an untreated SCI, mice with an SCI treated with lycopene had significantly reduced spinal cord tissue water content and BSCB permeability. Furthermore, motor function of mice with an SCI was also greatly improved by lycopene administration. The expression of the proinflammatory factors TNF-α and NF-kB increased markedly 48 h after SCI, and their upregulation was significantly attenuated by lycopene treatment. The expression of molecules that protect tight junctions, zonula occluden-1 and claudin-5, was upregulated by lycopene treatment after SCI. Taken together, these results clearly indicate that lycopene attenuated SCI by promoting repair of the damaged BSCB, so lycopene is a novel and promising treatment for SCI in humans.

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.

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.

Cortical control of intraspinal microstimulation: Toward a new approach for restoration of function after spinal cord injury.

PubMed

Shahdoost, Shahab; Frost, Shawn; Dunham, Caleb; DeJong, Stacey; Barbay, Scott; Nudo, Randolph; Mohseni, Pedram

2015-08-01

Approximately 6 million people in the United States are currently living with paralysis in which 23% of the cases are related to spinal cord injury (SCI). Miniaturized closed-loop neural interfaces have the potential for restoring function and mobility lost to debilitating neural injuries such as SCI by leveraging recent advancements in bioelectronics and a better understanding of the processes that underlie functional and anatomical reorganization in an injured nervous system. This paper describes our current progress toward developing a miniaturized brain-machine-spinal cord interface (BMSI) that converts in real time the neural command signals recorded from the cortical motor regions to electrical stimuli delivered to the spinal cord below the injury level. Using a combination of custom integrated circuit (IC) technology for corticospinal interfacing and field-programmable gate array (FPGA)-based technology for embedded signal processing, we demonstrate proof-of-concept of distinct muscle pattern activation via intraspinal microstimulation (ISMS) controlled in real time by intracortical neural spikes in an anesthetized laboratory rat.

NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury

PubMed Central

Yang, Zhaoyang; Zhang, Aifeng; Duan, Hongmei; Zhang, Sa; Hao, Peng; Ye, Keqiang; Sun, Yi E.; Li, Xiaoguang

2015-01-01

Neural stem cells (NSCs) in the adult mammalian central nervous system (CNS) hold the key to neural regeneration through proper activation, differentiation, and maturation, to establish nascent neural networks, which can be integrated into damaged neural circuits to repair function. However, the CNS injury microenvironment is often inhibitory and inflammatory, limiting the ability of activated NSCs to differentiate into neurons and form nascent circuits. Here we report that neurotrophin-3 (NT3)-coupled chitosan biomaterial, when inserted into a 5-mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous NSCs in the injured spinal cord. Through slow release of NT3, the biomaterial attracted NSCs to migrate into the lesion area, differentiate into neurons, and form functional neural networks, which interconnected severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis could be a novel strategy for treatment of spinal cord injury. PMID:26460015

Effects of glycine on motor performance in rats after traumatic spinal cord injury.

PubMed

Gonzalez-Piña, Rigoberto; Nuño-Licona, Alberto

2007-01-01

It has been reported that glycine improves some functions lost after spinal cord injury (SCI). In order to assess the effects of glycine administration on motor performance after SCI, we used fifteen male Wistar rats distributed into three groups: sham (n = 3), spinal-cord injury (n = 6,) and spinal cord injury + glycine (n = 6). Motor performance was assessed using the beam-walking paradigm and footprint analysis. Results showed that for all animals with spinal-cord injury, scores in the beam-walking increased, which is an indication of increased motor deficit. In addition, footprint analysis showed a decrease in stride length and an increase in stride angle, additional indicators of motor deficit. These effects trended towards recovery after 8 weeks of recording and trended toward improvement by glycine administration; the effect was not significant. These results suggest that glycine replacement alone is not sufficient to improve the motor deficits that occur after SCI.

Spinal microcircuits comprising dI3 interneurons are necessary for motor functional recovery following spinal cord transection

PubMed Central

Bui, Tuan V; Stifani, Nicolas; Akay, Turgay; Brownstone, Robert M

2016-01-01

The spinal cord has the capacity to coordinate motor activities such as locomotion. Following spinal transection, functional activity can be regained, to a degree, following motor training. To identify microcircuits involved in this recovery, we studied a population of mouse spinal interneurons known to receive direct afferent inputs and project to intermediate and ventral regions of the spinal cord. We demonstrate that while dI3 interneurons are not necessary for normal locomotor activity, locomotor circuits rhythmically inhibit them and dI3 interneurons can activate these circuits. Removing dI3 interneurons from spinal microcircuits by eliminating their synaptic transmission left locomotion more or less unchanged, but abolished functional recovery, indicating that dI3 interneurons are a necessary cellular substrate for motor system plasticity following transection. We suggest that dI3 interneurons compare inputs from locomotor circuits with sensory afferent inputs to compute sensory prediction errors that then modify locomotor circuits to effect motor recovery. DOI: http://dx.doi.org/10.7554/eLife.21715.001 PMID:27977000

'Full dose' reirradiation of human cervical spinal cord.

PubMed

Ryu, S; Gorty, S; Kazee, A M; Bogart, J; Hahn, S S; Dalal, P S; Chung, C T; Sagerman, R H

2000-02-01

With the progress of modern multimodality cancer treatment, retreatment of late recurrences or second tumors became more commonly encountered in management of patients with cancer. Spinal cord retreatment with radiation is a common problem in this regard. Because radiation myelopathy may result in functional deficits, many oncologists are concerned about radiation-induced myelopathy when retreating tumors located within or immediately adjacent to the previous radiation portal. The treatment decision is complicated because it requires a pertinent assessment of prognostic factors with and without reirradiation, radiobiologic estimation of recovery of occult spinal cord damage from the previous treatment, as well as interactions because of multimodality treatment. Recent studies regarding reirradiation of spinal cord in animals using limb paralysis as an endpoint have shown substantial and almost complete recovery of spinal cord injury after a sufficient time after the initial radiotherapy. We report a case of "full" dose reirradiation of the entire cervical spinal cord in a patient who has not developed clinically detectable radiation-induced myelopathy on long-term follow-up of 17 years after the first radiotherapy and 5 years after the second radiotherapy.

The mechanism of Naringin-enhanced remyelination after spinal cord injury

PubMed Central

Rong, Wei; Pan, Yong-wei; Cai, Xu; Song, Fei; Zhao, Zhe; Xiao, Song-hua; Zhang, Cheng

2017-01-01

Our previous study revealed that intragastric administration of naringin improved remyelination in rats with spinal cord injury and promoted the recovery of neurological function of the injured spinal cord. This study sought to reveal the mechanisms by which naringin improves oligodendrocyte precursor cell differentiation and maturation, and promotes remyelination. Spinal cord injury was induced in rats by the weight-drop method. Naringin was intragastrically administered daily (20, 40 mg/kg) for 4 weeks after spinal cord injury induction. Behavioral assessment, histopathological staining, immunofluorescence spectroscopy, ultrastructural analysis and biochemical assays were employed. Naringin treatment remarkably mitigated demyelination in the white matter, increased the quality of myelinated nerve fibers and myelin sheath thickness, promoted oligodendrocyte precursor cell differentiation by upregulating the expression of NKx2.2 and 2′3′-cyclic nucleotide 3′-phosphodiesterase, and inhibited β-catenin expression and glycogen synthase kinase-3β (GSK-3β) phosphorylation. These findings indicate that naringin treatment regulates oligodendrocyte precursor cell differentiation and promotes remyelination after spinal cord injury through the β-catenin/GSK-3β signaling pathway. PMID:28469664

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.

[The influence of non-invasive electrical stimulation of the spinal cord on the locomotor function of patients presenting with movement disorders of central genesis].

PubMed

Balykin, M V; Yakupov, R N; Mashin, V V; Kotova, E Yu; Balykin, Yu M; Gerasimenko, Yu P

The objective of the present study was to evaluate the influence of non-invasive (transcutaneous) electrical spinal cord stimulation on the locomotor function of the patients suffering from movement disorders. The study involved 10 patients of both sexes at the age from 32 to 70 years (including 40% of men and 60% of women) presenting with the compromised locomotor function of varying severity associated with the disturbances of cerebral blood circulation caused either by an injury to the brain and spinal cord or by stroke. The transcutaneous electrical spinal cord stimulation was applied using different frequency regimes with the placement of the electrodes in the projection onto the region of TXI-TXII vertebrae. The active factors were bipolar electrical stimuli 0.5 ms in duration; the current strength was chosen for each patient on an individual basis taking into consideration its threshold level. Electromyograms and evoked motor responses of selected muscles, viz. m. rectus femoris, m.biceps femoris, m. tibialis anterior, and m.gastrocnemius were recorded with the use of the 'Neuro-MVP-8 eight-channel electromyography' ('Neurosoft', Russia). The data obtained give evidence that the stimulation of the spinal cord with a frequency of 1 Hz induces reflectory responses with monosynaptic and polysynaptic components in the muscles of the lower extremities, with the thresholds of these responses being significantly higher in the patients presenting with serious neurological problems. Stimulation with the frequencies of 5 and 30 Hz caused in the patients with paresis the involuntary movement of the legs the characteristics of which were similar to those of the locomotor movements. It has been demonstrated that the application of transcutaneous electrical spinal cord stimulation leads to increased excitability of the lumbar spinal neural structures of the patients. The study has shown the possibility of regulation of the locomotor functions in the patients presenting with movement disorders of central genesis by means of non-invasive electrical stimulation of the spinal cord.

Design and criteria of electrospun fibrous scaffolds for the treatment of spinal cord injury

PubMed Central

Vigani, Barbara; Rossi, Silvia; Sandri, Giuseppina; Bonferoni, Maria Cristina; Ferrari, Franca

2017-01-01

The complex pathophysiology of spinal cord injury may explain the current lack of an effective therapeutic approach for the regeneration of damaged neuronal cells and the recovery of motor functions. Many efforts have been performed to design and develop suitable scaffolds for spinal cord regeneration, keeping in mind that the reconstruction of a pro-regenerative environment is the key challenge for an effective neurogenesis. The aim of this review is to outline the main features of an ideal scaffold, based on biomaterials, produced by the electrospinning technique and intended for the spinal cord regeneration. An overview of the polymers more investigated in the production of neural fibrous scaffolds is also provided. PMID:29239316

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.

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

Noradrenergic innervation of the rat spinal cord caudal to a complete spinal cord transection: effects of olfactory ensheathing glia.

PubMed

Takeoka, Aya; Kubasak, Marc D; Zhong, Hui; Kaplan, Jennifer; Roy, Roland R; Phelps, Patricia E

2010-03-01

Transplantation of olfactory bulb-derived olfactory ensheathing glia (OEG) combined with step training improves hindlimb locomotion in adult rats with a complete spinal cord transection. Spinal cord injury studies use the presence of noradrenergic (NA) axons caudal to the injury site as evidence of axonal regeneration and we previously found more NA axons just caudal to the transection in OEG- than media-injected spinal rats. We therefore hypothesized that OEG transplantation promotes descending coeruleospinal regeneration that contributes to the recovery of hindlimb locomotion. Now we report that NA axons are present throughout the caudal stump of both media- and OEG-injected spinal rats and they enter the spinal cord from the periphery via dorsal and ventral roots and along large penetrating blood vessels. These results indicate that the presence of NA fibers in the caudal spinal cord is not a reliable indicator of coeruleospinal regeneration. We then asked if NA axons appose cholinergic neurons associated with motor functions, i.e., central canal cluster and partition cells (active during fictive locomotion) and somatic motor neurons (SMNs). We found more NA varicosities adjacent to central canal cluster cells, partition cells, and SMNs in the lumbar enlargement of OEG- than media-injected rats. As non-synaptic release of NA is common in the spinal cord, more associations between NA varicosities and motor-associated cholinergic neurons in the lumbar spinal cord may contribute to the improved treadmill stepping observed in OEG-injected spinal rats. This effect could be mediated through direct association with SMNs and/or indirectly via cholinergic interneurons. Copyright 2009 Elsevier Inc. All rights reserved.

Functional and clinical outcomes of telemedicine in patients with spinal cord injury.

PubMed

Dallolio, Laura; Menarini, Mauro; China, Sandra; Ventura, Manfredi; Stainthorpe, Andy; Soopramanien, Anba; Rucci, Paola; Fantini, Maria Pia

2008-12-01

To compare the 6-month outcomes of telerehabilitation intervention with those of standard care for spinal cord injury (SCI). Multicenter randomized controlled trial. Home, nursing, or unspecialized hospital care provided after discharge from a spinal cord unit. Adult patients with nonprogressive, complete, or incomplete SCI discharged for the first time from the spinal cord unit to their homes (Belgium and Italy) or to their homes or another facility (England). All patients received the standard care they would have normally received after discharge from the spinal cord unit. In addition, patients in the telemedicine group received 8 telemedicine weekly sessions in the first 2 months, followed by biweekly telemedicine sessions for 4 months. Functional status at 6 months, clinical complications during the postdischarge period, and patient satisfaction. No significant differences in the occurrence of clinical complications were found between the study groups. A higher improvement of functional scores in the telemedicine group was found only at the Italian site: FIM total score 3.38+/-4.43 (controls) versus 7.69+/-6.88 (telemedicine group), FIM motor score 3.24+/-4.38 (controls) versus 7.55+/-7.00 (telemedicine group; P<.05). Items contributing to this difference were grooming, dressing upper body, dressing lower body, and bed/chair/wheelchair transfer. Higher satisfaction with care was reported by patients in the telemedicine group across all sites. Our study provides some of the first quantitative evidence, based on results from 1 site, that telerehabilitation may offer benefits to patients discharged from a spinal cord unit compared with standard care in terms of functional improvement. Further research is warranted to confirm or disprove this finding.

Robot-Assisted Training of Arm and Hand Movement Shows Functional Improvements for Incomplete Cervical Spinal Cord Injury.

PubMed

Francisco, Gerard E; Yozbatiran, Nuray; Berliner, Jeffrey; OʼMalley, Marcia K; Pehlivan, Ali Utku; Kadivar, Zahra; Fitle, Kyle; Boake, Corwin

2017-10-01

The aim of the study was to demonstrate the feasibility, tolerability, and effectiveness of robotic-assisted arm training in incomplete chronic tetraplegia. Pretest/posttest/follow-up was conducted. Ten individuals with chronic cervical spinal cord injury were enrolled. Participants performed single degree-of-freedom exercise of upper limbs at an intensity of 3-hr per session for 3 times a week for 4 wks with MAHI Exo-II. Arm and hand function tests (Jebsen-Taylor Hand Function Test, Action Research Arm Test), strength of upper limb (upper limb motor score, grip, and pinch strength), and independence in daily living activities (Spinal Cord Independence Measure II) were performed at baseline, end of training, and 6 mos later. After 12 sessions of training, improvements in arm and hand functions were observed. Jebsen-Taylor Hand Function Test (0.14[0.04]-0.21[0.07] items/sec, P = 0.04), Action Research Arm Test (30.7[3.8]-34.3[4], P = 0.02), American Spinal Injury Association upper limb motor score (31.5[2.3]-34[2.3], P = 0.04) grip (9.7[3.8]-12[4.3] lb, P = 0.02), and pinch strength (4.5[1.1]-5.7[1.2] lb, P = 0.01) resulted in significant increases. Some gains were maintained at 6 mos. No change in Spinal Cord Independence Measure II scores and no adverse events were observed. Results from this pilot study suggest that repetitive training of arm movements with MAHI Exo-II exoskeleton is safe and has potential to be an adjunct treatment modality in rehabilitation of persons with spinal cord injury with mild to moderate impaired arm functions.

Engaging Cervical Spinal Cord Networks to Reenable Volitional Control of Hand Function in Tetraplegic Patients.

PubMed

Lu, Daniel C; Edgerton, V Reggie; Modaber, Morteza; AuYong, Nicholas; Morikawa, Erika; Zdunowski, Sharon; Sarino, Melanie E; Sarrafzadeh, Majid; Nuwer, Marc R; Roy, Roland R; Gerasimenko, Yury

2016-11-01

Paralysis of the upper limbs from spinal cord injury results in an enormous loss of independence in an individual's daily life. Meaningful improvement in hand function is rare after 1 year of tetraparesis. Therapeutic developments that result in even modest gains in hand volitional function will significantly affect the quality of life for patients afflicted with high cervical injury. The ability to neuromodulate the lumbosacral spinal circuitry via epidural stimulation in regaining postural function and volitional control of the legs has been recently shown. A key question is whether a similar neuromodulatory strategy can be used to improve volitional motor control of the upper limbs, that is, performance of motor tasks considered to be less "automatic" than posture and locomotion. In this study, the effects of cervical epidural stimulation on hand function are characterized in subjects with chronic cervical cord injury. Herein we show that epidural stimulation can be applied to the chronic injured human cervical spinal cord to promote volitional hand function. Two subjects implanted with a cervical epidural electrode array demonstrated improved hand strength (approximately 3-fold) and volitional hand control in the presence of epidural stimulation. The present data are sufficient to suggest that hand motor function in individuals with chronic tetraplegia can be improved with cervical cord neuromodulation and thus should be comprehensively explored as a possible clinical intervention. © The Author(s) 2016.

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.

Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia

NASA Technical Reports Server (NTRS)

Zeitzer, J. M.; Ayas, N. T.; Shea, S. A.; Brown, R.; Czeisler, C. A.

2000-01-01

The human circadian timing system regulates the temporal organization of several endocrine functions, including the production of melatonin (via a neural pathway that includes the spinal cord), TSH, and cortisol. In traumatic spinal cord injury, afferent and efferent circuits that influence the basal production of these hormones may be disrupted. We studied five subjects with chronic spinal cord injury (three tetraplegic and two paraplegic, all neurologically complete injuries) under stringent conditions in which the underlying circadian rhythmicity of these hormones could be examined. Melatonin production was absent in the three tetraplegic subjects with injury to their lower cervical spinal cord and was of normal amplitude and timing in the two paraplegic subjects with injury to their upper thoracic spinal cord. The amplitude and the timing of TSH and cortisol rhythms were robust in the paraplegics and in the tetraplegics. Our results indicate that neurologically complete cervical spinal injury results in the complete loss of pineal melatonin production and that neither the loss of melatonin nor the loss of spinal afferent information disrupts the rhythmicity of cortisol or TSH secretion.

The recovery of 5-HT transporter and 5-HT immunoreactivity in injured rat spinal cord.

PubMed

Saruhashi, Yasuo; Matsusue, Yoshitaka; Fujimiya, Mineko

2009-09-01

Experimental spinal cord injury. To determine the role of serotonin (5-HT) and 5-HT transporter in recovery from spinal cord injury. We examined 5-HT and 5-HT transporter of spinal cord immunohistologically and assessed locomotor recovery after extradural compression at the thoracic (T8) spinal cord in 21 rats. Eighteen rats had laminectomy and spinal cord injury, while the remaining three rats received laminectomy only. All rats were evaluated every other day for 4 weeks, using a 0-14 point scale open field test. Extradural compression markedly reduced mean hindlimbs scores from 14 to 1.5 +/- 2.0 (mean +/- standard error of mean). The rats recovered apparently normal walking by 4 weeks. The animals were perfused with fixative 1-3 days, 1, 2 and 4 weeks (three rats in each) after a spinal cord injury. The 5-HT transporter immunohistological study revealed a marked reduction of 5-HT transporter-containing terminals by 1 day after injury. By 4 weeks after injury, 5-HT transporter immunoreactive terminals returned to the control level. The 5-HT immunohistological study revealed a reduction of 5-HT-containing terminals by 1 week after injury. By 4 weeks after injury, 5-HT immunoreactive fibers and terminals returned to the control level. We estimated the recovery of 5-HT transporter and 5-HT neural elements in lumbosacral ventral horn by ranking 5-HT transporter and 5-HT staining intensity and counting 5-HT and 5-HT transporter terminals. The return of 5-HT transporter and 5-HT immunoreactivity of the lumbosacral ventral horn correlated with locomotor recovery, while 5-HT transporter showed closer relationship with locomotor recovery than 5-HT. The presence of 5-HT transporter indicates that the 5-HT fibers certainly function. This study shows that return of the function of 5-HT fibers predict the time course and extent of locomotory recovery after thoracic spinal cord injury.

Retained differentiation capacity of human skeletal muscle satellite cells from spinal cord-injured individuals.

PubMed

Savikj, Mladen; Ruby, Maxwell A; Kostovski, Emil; Iversen, Per O; Zierath, Juleen R; Krook, Anna; Widegren, Ulrika

2018-06-01

Despite the well-known role of satellite cells in skeletal muscle plasticity, the effect of spinal cord injury on their function in humans remains unknown. We determined whether spinal cord injury affects the intrinsic ability of satellite cells to differentiate and produce metabolically healthy myotubes. We obtained vastus lateralis biopsies from eight spinal cord-injured and six able-bodied individuals. Satellite cells were isolated, grown and differentiated in vitro. Gene expression was measured by quantitative PCR. Abundance of differentiation markers and regulatory proteins was determined by Western blotting. Protein synthesis and fatty acid oxidation were measured by radioactive tracer-based assays. Activated satellite cells (myoblasts) and differentiated myotubes derived from skeletal muscle of able-bodied and spinal cord-injured individuals expressed similar (P > 0.05) mRNA levels of myogenic regulatory factors. Myogenic differentiation factor 1 expression was higher in myoblasts from spinal cord-injured individuals. Desmin and myogenin protein content was increased upon differentiation in both groups, while myotubes from spinal cord-injured individuals contained more type I and II myosin heavy chain. Phosphorylated and total protein levels of Akt-mechanistic target of rapamycin and forkhead box protein O signalling axes and protein synthesis rate in myotubes were similar (P > 0.05) between groups. Additionally, fatty acid oxidation of myotubes from spinal cord-injured individuals was unchanged (P > 0.05) compared to able-bodied controls. Our results indicate that the intrinsic differentiation capacity of satellite cells and metabolic characteristics of myotubes are preserved following spinal cord injury. This may inform potential interventions targeting satellite cell activation to alleviate skeletal muscle atrophy. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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

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.

Targeting L-Selectin to Improve Neurologic and Urologic Function After Spinal Cord Injury

DTIC Science & Technology

2014-10-01

doses of DFA, male C57BL/6 mice were subjected to a 2g weight dropped 7.5 cm onto the exposed spinal cord at the thoracic 9 vertebral level (mild...detect the absence of L-selectin on leukocytes 1 day post-SCI. Male C57BL/6 mice were subjected to a 2g weight dropped 7.5 cm onto the exposed spinal...subjected to a 2g weight dropped 7.5 cm onto the exposed spinal cord at the thoracic 9 vertebral level. DFA (40mg/kg) or vehicle was administered

Targeting Lumbar Spinal Neural Circuitry by Epidural Stimulation to Restore Motor Function After Spinal Cord Injury.

PubMed

Minassian, Karen; McKay, W Barry; Binder, Heinrich; Hofstoetter, Ursula S

2016-04-01

Epidural spinal cord stimulation has a long history of application for improving motor control in spinal cord injury. This review focuses on its resurgence following the progress made in understanding the underlying neurophysiological mechanisms and on recent reports of its augmentative effects upon otherwise subfunctional volitional motor control. Early work revealed that the spinal circuitry involved in lower-limb motor control can be accessed by stimulating through electrodes placed epidurally over the posterior aspect of the lumbar spinal cord below a paralyzing injury. Current understanding is that such stimulation activates large-to-medium-diameter sensory fibers within the posterior roots. Those fibers then trans-synaptically activate various spinal reflex circuits and plurisegmentally organized interneuronal networks that control more complex contraction and relaxation patterns involving multiple muscles. The induced change in responsiveness of this spinal motor circuitry to any residual supraspinal input via clinically silent translesional neural connections that have survived the injury may be a likely explanation for rudimentary volitional control enabled by epidural stimulation in otherwise paralyzed muscles. Technological developments that allow dynamic control of stimulation parameters and the potential for activity-dependent beneficial plasticity may further unveil the remarkable capacity of spinal motor processing that remains even after severe spinal cord injuries.

Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats.

PubMed

Sabino, Luzzi; Maria, Crovace Alberto; Luca, Lacitignola; Valerio, Valentini; Edda, Francioso; Giacomo, Rossi; Gloria, Invernici; Juan, Galzio Renato; Antonio, Crovace

2018-01-01

Proof of the efficacy and safety of a xenogeneic mesenchymal stem cell (MSCs) transplant for spinal cord injury (SCI) may theoretically widen the spectrum of possible grafts for neuroregeneration. Twenty rats were submitted to complete spinal cord transection. Ovine bone marrow MSCs, retrovirally transfected with red fluorescent protein and not previously induced for neuroglial differentiation, were applied in 10 study rats (MSCG). Fibrin glue was injected in 10 control rats (FGG). All rats were evaluated on a weekly basis and scored using the Basso-Beattie-Bresnahan (BBB) locomotor scale for 10 weeks, when the collected data were statistically analyzed. The spinal cords were then harvested and analyzed with light microscopy, immunohistochemistry, and immunofluorescence. Ovine MSCs culture showed positivity for Nestin. MSCG had a significant and durable recovery of motor functions ( P <.001). Red fluorescence was found at the injury sites in MSCG. Positivity for Nestin, tubulin βIII, NG2 glia, neuron-specific enolase, vimentin, and 200 kD neurofilament were also found at the same sites. Xenogeneic ovine bone marrow MSCs proved capable of engrafting into the injured rat spinal cord. Transdifferentiation into a neuroglial phenotype was able to support partial functional recovery.

Engraftment, neuroglial transdifferentiation and behavioral recovery after complete spinal cord transection in rats

PubMed Central

Sabino, Luzzi; Maria, Crovace Alberto; Luca, Lacitignola; Valerio, Valentini; Edda, Francioso; Giacomo, Rossi; Gloria, Invernici; Juan, Galzio Renato; Antonio, Crovace

2018-01-01

Background: Proof of the efficacy and safety of a xenogeneic mesenchymal stem cell (MSCs) transplant for spinal cord injury (SCI) may theoretically widen the spectrum of possible grafts for neuroregeneration. Methods: Twenty rats were submitted to complete spinal cord transection. Ovine bone marrow MSCs, retrovirally transfected with red fluorescent protein and not previously induced for neuroglial differentiation, were applied in 10 study rats (MSCG). Fibrin glue was injected in 10 control rats (FGG). All rats were evaluated on a weekly basis and scored using the Basso–Beattie–Bresnahan (BBB) locomotor scale for 10 weeks, when the collected data were statistically analyzed. The spinal cords were then harvested and analyzed with light microscopy, immunohistochemistry, and immunofluorescence. Results: Ovine MSCs culture showed positivity for Nestin. MSCG had a significant and durable recovery of motor functions (P <.001). Red fluorescence was found at the injury sites in MSCG. Positivity for Nestin, tubulin βIII, NG2 glia, neuron-specific enolase, vimentin, and 200 kD neurofilament were also found at the same sites. Conclusions: Xenogeneic ovine bone marrow MSCs proved capable of engrafting into the injured rat spinal cord. Transdifferentiation into a neuroglial phenotype was able to support partial functional recovery. PMID:29497572

Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses

PubMed Central

Mishra, Asht M.; Pal, Ajay; Gupta, Disha

2017-01-01

Key points Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord.The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone.Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal.Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord. Abstract Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for protocols that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested the effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology experiments support the hypothesis that paired stimulation is mediated by convergence of descending motor circuits and large diameter afferents in the spinal cord. The large effect size of this protocol and the conservation of the circuits being manipulated between rats and humans makes it worth pursuing for recovery of sensorimotor function after injury to the central nervous system. PMID:28752624

Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses.

PubMed

Mishra, Asht M; Pal, Ajay; Gupta, Disha; Carmel, Jason B

2017-11-15

Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord. The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone. Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal. Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord. Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for protocols that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested the effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology experiments support the hypothesis that paired stimulation is mediated by convergence of descending motor circuits and large diameter afferents in the spinal cord. The large effect size of this protocol and the conservation of the circuits being manipulated between rats and humans makes it worth pursuing for recovery of sensorimotor function after injury to the central nervous system. © 2017 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Contributions of identifiable neurons and neuron classes to lamprey vertebrate neurobiology.

PubMed

Buchanan, J T

2001-03-01

Among the advantages offered by the lamprey brainstem and spinal cord for studies of the structure and function of the nervous system is the unique identifiability of several pairs of reticulospinal neurons in the brainstem. These neurons have been exploited in investigations of the patterns of sensory input to these cells and the patterns of their outputs to spinal neurons, but no doubt these cells could be used much more effectively in exploring their roles in descending control of the spinal cord. The variability of cell positions of neurons in the spinal cord has precluded the recognition of unique spinal neurons. However, classes of nerve cells can be readily defined and characterized within the lamprey spinal cord and this has led to progress in understanding the cellular and synaptic mechanisms of locomotor activity. In addition, both the identifiable reticulospinal cells and the various spinal nerve cell classes and their known synaptic interactions have been used to demonstrate the degree and specificity of regeneration within the lamprey nervous system. The lack of uniquely identifiable cells within the lamprey spinal cord has hampered progress in these areas, especially in gaining a full understanding of the locomotor network and how neuromodulation of the network is accomplished.

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

Transplantation of oligodendrocyte precursors and sonic hedgehog results in improved function and white matter sparing in the spinal cords of adult rats after contusion.

PubMed

Bambakidis, Nicholas C; Miller, Robert H

2004-01-01

A substantial cause of neurological disability in spinal cord injury is oligodendrocyte death leading to demyelination and axonal degeneration. Rescuing oligodendrocytes and preserving myelin is expected to result in significant improvement in functional outcome after spinal cord injury. Although previous investigators have used cellular transplantation of xenografted pluripotent embryonic stem cells and observed improved functional outcome, these transplants have required steroid administration and only a minority of these cells develop into oligodendrocytes. The objective of the present study was to determine whether allografts of oligodendrocyte precursors transplanted into an area of incomplete spinal cord contusion would improve behavioral and electrophysiological measures of spinal cord function. Additional treatment incorporated the use of the glycoprotein molecule Sonic hedgehog (Shh), which has been shown to play a critical role in oligodendroglial development and induce proliferation of endogenous neural precursors after spinal cord injury. Laboratory study. Moderate spinal cord contusion injury was produced in 39 adult rats at T9-T10. Ten animals died during the course of the study. Nine rats served as contusion controls (Group 1). Six rats were treated with oligodendrocyte precursor transplantation 5 days after injury (Group 2). The transplanted cells were isolated from newborn rat pups using immunopanning techniques. Another eight rats received an injection of recombinant Shh along with the oligodendrocyte precursors (Group 3), while six more rats were treated with Shh alone (Group 4). Eight additional rats received only T9 laminectomies to serve as noninjured controls (Group 0). Animals were followed for 28 days. After an initial complete hindlimb paralysis, rats of all groups receiving a contusive injury recovered substantial function within 1 week. By 28 days, rats in Groups 2 and 3 scored 4.7 and 5.8 points better on the Basso, Beattie, Bresnahan (BBB) open field locomotor score than rats in group 1 (Groups 2 and 3=18.2 and 19.4 points, respectively, after 28 days vs. Group 1=13.6 points; p=.015). Rats in Group 4 scored no better than those in Group 1 (BBB=16.4). Motor evoked potential (MEP) recordings revealed a strong trend towards significant improvement in latency measurements in all treatment groups compared with controls at 28 days, although three animals in Group 1 and two animals in Group 3 were not recordable. Histological examination demonstrated significantly more spared white matter in the same groups that correlated with the improvements in BBB scores and MEP latencies. Immunohistochemical analysis showed the survival, proliferation and migration of the transplanted cells, as well as the induction of proliferating endogenous neural precursor cells in animals treated with Shh. These findings suggest that the transplantation of oligodendrocyte precursors may improve axonal conduction and spinal cord function in the injured spinal cord. The benefits seem more pronounced with the addition of Shh, and the addition of Shh alone results in the proliferation of an endogenous population of neural precursor cells.

Reproducibility of resting state spinal cord networks in healthy volunteers at 7 Tesla.

PubMed

Barry, Robert L; Rogers, Baxter P; Conrad, Benjamin N; Smith, Seth A; Gore, John C

2016-06-01

We recently reported our findings of resting state functional connectivity in the human spinal cord: in a cohort of healthy volunteers we observed robust functional connectivity between left and right ventral (motor) horns and between left and right dorsal (sensory) horns (Barry et al., 2014). Building upon these results, we now quantify the within-subject reproducibility of bilateral motor and sensory networks (intraclass correlation coefficient=0.54-0.56) and explore the impact of including frequencies up to 0.13Hz. Our results suggest that frequencies above 0.08Hz may enhance the detectability of these resting state networks, which would be beneficial for practical studies of spinal cord functional connectivity. Copyright © 2016 Elsevier Inc. All rights reserved.

Differential fMRI Activation Patterns to Noxious Heat and Tactile Stimuli in the Primate Spinal Cord

PubMed Central

Yang, Pai-Feng; Wang, Feng

2015-01-01

Mesoscale local functional organizations of the primate spinal cord are largely unknown. Using high-resolution fMRI at 9.4 T, we identified distinct interhorn and intersegment fMRI activation patterns to tactile versus nociceptive heat stimulation of digits in lightly anesthetized monkeys. Within a spinal segment, 8 Hz vibrotactile stimuli elicited predominantly fMRI activations in the middle part of ipsilateral dorsal horn (iDH), along with significantly weaker activations in ipsilateral (iVH) and contralateral (cVH) ventral horns. In contrast, nociceptive heat stimuli evoked widespread strong activations in the superficial part of iDH, as well as in iVH and contralateral dorsal (cDH) horns. As controls, only weak signal fluctuations were detected in the white matter. The iDH responded most strongly to both tactile and heat stimuli, whereas the cVH and cDH responded selectively to tactile versus nociceptive heat, respectively. Across spinal segments, iDH activations were detected in three consecutive segments in both tactile and heat conditions. Heat responses, however, were more extensive along the cord, with strong activations in iVH and cDH in two consecutive segments. Subsequent subunit B of cholera toxin tracer histology confirmed that the spinal segments showing fMRI activations indeed received afferent inputs from the stimulated digits. Comparisons of the fMRI signal time courses in early somatosensory area 3b and iDH revealed very similar hemodynamic stimulus–response functions. In summary, we identified with fMRI distinct segmental networks for the processing of tactile and nociceptive heat stimuli in the cervical spinal cord of nonhuman primates. SIGNIFICANCE STATEMENT This is the first fMRI demonstration of distinct intrasegmental and intersegmental nociceptive heat and touch processing circuits in the spinal cord of nonhuman primates. This study provides novel insights into the local functional organizations of the primate spinal cord for pain and touch, information that will be valuable for designing and optimizing therapeutic interventions for chronic pain management. PMID:26203144

Axon regeneration can facilitate or suppress hindlimb function after olfactory ensheathing glia transplantation.

PubMed

Takeoka, Aya; Jindrich, Devin L; Muñoz-Quiles, Cintia; Zhong, Hui; van den Brand, Rubia; Pham, Daniel L; Ziegler, Matthias D; Ramón-Cueto, Almudena; Roy, Roland R; Edgerton, V Reggie; Phelps, Patricia E

2011-03-16

Reports based primarily on anatomical evidence suggest that olfactory ensheathing glia (OEG) transplantation promotes axon regeneration across a complete spinal cord transection in adult rats. Based on functional, electrophysiological, and anatomical assessments, we found that OEG promoted axon regeneration across a complete spinal cord transection and that this regeneration altered motor responses over time. At 7 months after transection, 70% of OEG-treated rats showed motor-evoked potentials in hindlimb muscles after transcranial electric stimulation. Furthermore, a complete spinal cord retransection performed 8 months after injury demonstrated that this axon regeneration suppressed locomotor performance and decreased the hypersensitive hindlimb withdrawal response to mechanical stimulation. OEG transplantation alone promoted reorganization of lumbosacral locomotor networks and, when combined with long-term training, enhanced some stepping measures. These novel findings demonstrate that OEG promote regeneration of mature axons across a complete transection and reorganization of spinal circuitry, both of which contribute to sensorimotor function.

Axon Regeneration Can Facilitate or Suppress Hindlimb Function after Olfactory Ensheathing Glia Transplantation

PubMed Central

Takeoka, Aya; Jindrich, Devin L.; Muñoz-Quiles, Cintia; Zhong, Hui; van den Brand, Rubia; Pham, Daniel L.; Ziegler, Matthias D.; Ramón-Cueto, Almudena; Roy, Roland R.; Edgerton, V. Reggie

2011-01-01

Reports based primarily on anatomical evidence suggest that olfactory ensheathing glia (OEG) transplantation promotes axon regeneration across a complete spinal cord transection in adult rats. Based on functional, electrophysiological, and anatomical assessments, we found that OEG promoted axon regeneration across a complete spinal cord transection and that this regeneration altered motor responses over time. At 7 months after transection, 70% of OEG-treated rats showed motor-evoked potentials in hindlimb muscles after transcranial electric stimulation. Furthermore, a complete spinal cord retransection performed 8 months after injury demonstrated that this axon regeneration suppressed locomotor performance and decreased the hypersensitive hindlimb withdrawal response to mechanical stimulation. OEG transplantation alone promoted reorganization of lumbosacral locomotor networks and, when combined with long-term training, enhanced some stepping measures. These novel findings demonstrate that OEG promote regeneration of mature axons across a complete transection and reorganization of spinal circuitry, both of which contribute to sensorimotor function. PMID:21411671

Initiation of bladder voiding with epidural stimulation in paralyzed, step trained rats.

PubMed

Gad, Parag N; Roy, Roland R; Zhong, Hui; Lu, Daniel C; Gerasimenko, Yury P; Edgerton, V Reggie

2014-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury.

Initiation of Bladder Voiding with Epidural Stimulation in Paralyzed, Step Trained Rats

PubMed Central

Gad, Parag N.; Roy, Roland R.; Zhong, Hui; Lu, Daniel C.; Gerasimenko, Yury P.; Edgerton, V. Reggie

2014-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury. PMID:25264607

Mediators of disability and hope for people with spinal cord injury.

PubMed

Phillips, Brian N; Smedema, Susan M; Fleming, Allison R; Sung, Connie; Allen, Michael G

2016-08-01

To test potential strength-based mediators of functional disability and hope in adults with spinal cord injury. Two hundred and forty-two participants with spinal cord injury were recruited for this study. The mean age of participants was 44.6 years (standard deviation = 13.2), and 66.1% were men. Participants completed a survey containing a demographic questionnaire, as well as measures of functional disability, hope, self-esteem, proactive coping, perceived social support and disability acceptance. Mediation analysis was conducted using a bootstrap test for multiple mediators. Proactive coping, self-esteem and perceived social support significantly mediated the relationship between functional disability and hope, while disability acceptance did not. The combination of mediators resulted in functional disability no longer being a significant predictor of hope. The strength-based constructs of proactive coping, self-esteem and social support appear effective in predicting hope regardless of severity of spinal cord injury. Functional disability was no longer predictive of hope after controlling for these strength-based constructs. Disability acceptance did not significantly add to the mediation model. These results provide further evidence for strength-based interventions in rehabilitation. Implications for Rehabilitation Strength-based constructs of proactive coping, self-esteem and social support are important factors for addressing hope following spinal cord injury, regardless of level of severity. Rehabilitation services providers should focus efforts on supporting clients in the accurate appraisal of predictable stressors and then generate means for addressing them as a form of proactive coping. Rehabilitation services providers must be cautious when addressing self-esteem to focus on perceived competence and learning processes rather than self-esteem directly or through the accomplishment of goals that may not be achieved. Knowing that social supports are related to hope post-spinal cord injury, it is important for rehabilitation services providers to recognize potential social supports early in the rehabilitation process and involve those social supports in the rehabilitation process when possible.

Repair of spinal cord injury with neuronal relays: From fetal grafts to neural stem cells.

PubMed

Bonner, Joseph F; Steward, Oswald

2015-09-04

Spinal cord injury (SCI) disrupts the long axonal tracts of the spinal cord leading to devastating loss of function. Cell transplantation in the injured spinal cord has the potential to lead to recovery after SCI via a variety of mechanisms. One such strategy is the formation of neuronal relays between injured long tract axons and denervated neurons. The idea of creating a neuronal relay was first proposed over 25 years ago when fetal tissue was first successfully transplanted into the injured rodent spinal cord. Advances in labeling of grafted cells and the development of neural stem cell culturing techniques have improved the ability to create and refine such relays. Several recent studies have examined the ability to create a novel neuronal circuit between injured axons and denervated targets. This approach is an alternative to long-distance regeneration of damaged axons that may provide a meaningful degree of recovery without direct recreation of lost pathways. This brief review will examine the contribution of fetal grafting to current advances in neuronal grafting. Of particular interest will be the ability of transplanted neurons derived from fetal grafts, neural precursor cells and neural stem cells to reconnect long distance motor and sensory pathways of the injured spinal cord. This article is part of a Special Issue entitled SI: Spinal cord injury. Copyright © 2015 Elsevier B.V. All rights reserved.

Exogenous BDNF enhances the integration of chronically injured axons that regenerate through a peripheral nerve grafted into a chondroitinase-treated spinal cord injury site

PubMed Central

Tom, Veronica J.; Sandrow-Feinberg, Harra R.; Miller, Kassi; Domitrovich, Cheryl; Bouyer, Julien; Zhukareva, Victoria; Klaw, Michelle C.; Lemay, Michel A.; Houlé, John D.

2016-01-01

Although axons lose some of their intrinsic capacity for growth after their developmental period, some axons retain the potential for regrowth after injury. When provided with a growth-promoting substrate such as a peripheral nerve graft (PNG), severed axons regenerate into and through the graft; however, they stop when they reach the glial scar at the distal graft-host interface that is rich with inhibitory chondroitin sulfate proteoglycans. We previously showed that treatment of a spinal cord injury site with chondroitinase (ChABC) allows axons within the graft to traverse the scar and reinnervate spinal cord, where they form functional synapses. While this improvement in outgrowth was significant, it still represented only a small percentage (<20%) of axons compared to the total number of axons that regenerated into the PNG. Here we tested whether providing exogenous brain-derived neurotrophic factor (BDNF) via lentivirus in tissue distal to the PNG would augment regeneration beyond a ChABC-treated glial interface. We found that ChABC treatment alone promoted axonal regeneration but combining ChABC with BDNF-lentivirus did not increase the number of axons that regenerated back into spinal cord. Combining BDNF with ChABC did increase the number of spinal cord neurons that were trans-synaptically activated during electrical stimulation of the graft, as indicated by c-Fos expression, suggesting that BDNF overexpression improved the functional significance of axons that did reinnervate distal spinal cord tissue. PMID:23022460

Frequency Mapping of Rat Spinal Cord at 7T

NASA Astrophysics Data System (ADS)

Chen, Evan; Rauscher, Alexander; Kozlowski, Piotr; Yung, Andrew

2012-10-01

The spinal cord is an integral part of the nervous system responsible for sensory, motor, and reflex control crucial to all bodily function. Due to its non-invasive nature, MRI is well matched for characterizing and imaging of spinal cord, and is used extensively for clinical applications. Recent developments in magnetic resonance imaging (MRI) at high field (7T) using phase represents a new approach of characterizing spinal cord myelin. Theory suggests that microstructure differences in myelinated white matter (WM) and non-myelinated gray matter (GM) affect MR phase, measurable frequency shifts. Data from pilot experiments using a multi-gradient echo (MGE) sequence to image rat spinal cords placed parallel to main magnetic field B0 has shown frequency shifts between not only between WM and GM, but also between specific WM tracts of the dorsal column, including the fasciculus gracilis, fasciculus cuneatus, and corticospinal tract. Using MGE, frequency maps at multiple echo times (TE) between 4ms and 22ms show a non-linear relationship between WM frequency, contrary to what was previously expected. These results demonstrate the effectiveness of MGE in revealing new information about spinal cord tissue microstructure, and lays important groundwork for in-vivo and human studies.

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

Real-time PCR quantification of gene expression in embryonic mouse tissue.

PubMed

Villalon, Eric; Schulz, David J; Waters, Samuel T

2014-01-01

The Gbx family of transcription factors consists of two closely related proteins GBX1 and GBX2. A defining feature of the GBX family is a highly conserved 60 amino acid DNA-binding domain, which differs by just two amino acids. Gbx1 and Gbx2 are co-expressed in several areas of the developing central nervous system including the forebrain, anterior hindbrain, and spinal cord, suggesting the potential for genetic redundancy. However, there is a spatiotemporal difference in expression of Gbx1 and Gbx2 in the forebrain and spinal cord. Gbx2 has been shown to play a critical role in positioning the midbrain/hindbrain boundary and developing anterior hindbrain, whereas gene-targeting experiments in mice have revealed an essential function for Gbx1 in the spinal cord for normal locomotion. To determine if Gbx2 could potentially compensate for a loss of Gbx1 in the developing spinal cord, we performed real-time PCR to examine levels of Gbx2 expression in Gbx1(-/-) spinal cord at embryonic day (E) 13.5, a developmental stage when Gbx2 is rapidly downregulated. We demonstrate that Gbx2 expression is elevated in the spinal cord of Gbx1(-/-) embryos.

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

[Evaluation of the role of combined TES-MEP and CSEP monitoring during the spinal surgery].

PubMed

Chen, Yu-guang; Peng, Xin-sheng; Wan, Yong; Yang, Jun-lin; Zheng, Zhao-min; Zou, Xue-nong; Li, Fo-bao; Shu, Hai-hua; Xia, Jie-hua; Dou, Yun-ling

2010-02-01

To evaluate of the role of transcranial electrical stimulation motor evoked potential (TES-MEP) in combination with cortical somatosensory evoked potential (CSEP) monitoring during the spinal surgery. TES-MEP on bilateral anterior tibial muscle and flexor hallucal brevis and CSEP on bilateral posterior tibial nerve were observed simultaneously on 293 patients during spinal surgery from July 2006 to April 2009. Intravenous anesthesia was employed in all the patients, a part of which were added low dose of sevoflurane or muscle relaxant. The results of TES-MEP, CSEP and combined monitoring were analyzed statistically. Pre-operative and post-operative motor and sensory functions of spinal cord were compared. Success rate of TES-MEP, CSEP and combined monitoring was 90.8%, 96.9% and 100% respectively. For the judgment of motor function of spinal cord, the sensitivity of TES-MEP and CSEP was 100% and 89.3% respectively and the specificity of 98.4% and 96.9%. The Youden index of the two methods was 0.984 and 0.862. For sensory function, the sensitivity of them was 76.7% and 93.3% respectively and the specificity of 98.7% and 98.0%. The Youden index was 0.754 and 0.913. The sensitivity of combined monitoring was 100%, with the specificity of 96.9%. The Youden index was 0.969. The precision of monitoring motor function of spinal cord with TES-MEP is higher than that with CSEP, however, for sensory function, CSEP is more precise. The sensitivity and precision of combined monitoring for spinal cord function were apparently better than that of unitary TES-MEP or CSEP. The combined TES-MEP and CSEP monitoring is a relatively ideal method.

Sexual Functioning in Men Living with a Spinal Cord Injury-A Narrative Literature Review.

PubMed

Sunilkumar, M M; Boston, Patricia; Rajagopal, M R

2015-01-01

Sexual dysfunction is a major concern for Indian men living with a spinal cord injury. To examine the literature related to sexuality traumatic cord injury and its impact on sexual functioning. Databases using Cumulative Index to Nursing and Allied Health Literature (CINAHL) 2000-2012, Medline 1989-2012, Applied Social Sciences Index and Abstracts (ASSIA) 1989-2012 and Google Scholar were the search engines used used for literature review. The search yielded a total of 457 articles and only 75 of them were found relevant. The minimum number of articles required to meet the inclusion criteria for this review was 25-30 articles. Out of the 75 articles, 33 were considered relevant or related to the topic of sexual functioning, spinal cord injury, and paraplegia. Six areas were identified: Sexual stigmatization, physiological barriers to sexual satisfaction, clinical aspects of sexual functioning, biomedical approaches to sexual dysfunction, partner satisfaction, and lack of accessibility to sexual education. Spinal cord injury and sexual functioning affects a large segment of the male Indian population, yet most current research focuses on quantitative measurement with the emphasis on ejaculatory dysfunction, orgasm impairment, incontinence, and other physiological dysfunction. Further research is needed to address the subjective accounts of patients themselves with respect to the emotional and social impact of sexual disability. This would help to identify the best possible outcomes for both treatment and rehabilitation.

Constitutively active 5-HT2/α1 receptors facilitate muscle spasms after human spinal cord injury

PubMed Central

D'Amico, Jessica M.; Murray, Katherine C.; Li, Yaqing; Chan, K. Ming; Finlay, Mark G.; Bennett, David J.

2013-01-01

In animals, the recovery of motoneuron excitability in the months following a complete spinal cord injury is mediated, in part, by increases in constitutive serotonin (5-HT2) and norepinephrine (α1) receptor activity, which facilitates the reactivation of calcium-mediated persistent inward currents (CaPICs) without the ligands serotonin and norepinephrine below the injury. In this study we sought evidence for a similar role of constitutive monoamine receptor activity in the development of spasticity in human spinal cord injury. In chronically injured participants with partially preserved sensory and motor function, the serotonin reuptake inhibitor citalopram facilitated long-lasting reflex responses (spasms) previously shown to be mediated by CaPICs, suggesting that in incomplete spinal cord injury, functional descending sources of monoamines are present to activate monoamine receptors below the lesion. However, in participants with motor or motor/sensory complete injuries, the inverse agonist cyproheptadine, which blocks both ligand and constitutive 5-HT2/α1 receptor activity, decreased long-lasting reflexes, whereas the neutral antagonist chlorpromazine, which only blocks ligand activation of these receptors, had no effect. When tested in noninjured control participants having functional descending sources of monoamines, chlorpromazine was effective in reducing CaPIC-mediated motor unit activity. On the basis of these combined results, it appears that in severe spinal cord injury, facilitation of persistent inward currents and muscle spasms is mainly mediated by the activation of constitutive 5-HT2 and α1 receptor activity. Drugs that more selectively block these constitutively active monoamine receptors may provide better oral control of spasticity, especially in motor complete spinal cord injury where reducing motoneuron excitability is the primary goal. PMID:23221402

Improvement of renal function after human umbilical cord mesenchymal stem cell treatment on chronic renal failure and thoracic spinal cord entrapment: a case report.

PubMed

Rahyussalim, Ahmad Jabir; Saleh, Ifran; Kurniawati, Tri; Lutfi, Andi Praja Wira Yudha

2017-11-30

Chronic renal failure is an important clinical problem with significant socioeconomic impact worldwide. Thoracic spinal cord entrapment induced by a metabolic yield deposit in patients with renal failure results in intrusion of nervous tissue and consequently loss of motor and sensory function. Human umbilical cord mesenchymal stem cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Over the past decade, advances in the field of regenerative medicine allowed development of cell therapies suitable for kidney repair. Mesenchymal stem cell studies in animal models of chronic renal failure have uncovered a unique potential of these cells for improving function and regenerating the damaged kidney. We report a case of a 62-year-old ethnic Indonesian woman previously diagnosed as having thoracic spinal cord entrapment with paraplegic condition and chronic renal failure on hemodialysis. She had diabetes mellitus that affected her kidneys and had chronic renal failure for 2 years, with creatinine level of 11 mg/dl, and no urinating since then. She was treated with human umbilical cord mesenchymal stem cell implantation protocol. This protocol consists of implantation of 16 million human umbilical cord mesenchymal stem cells intrathecally and 16 million human umbilical cord mesenchymal stem cells intravenously. Three weeks after first intrathecal and intravenous implantation she could move her toes and her kidney improved. Her creatinine level decreased to 9 mg/dl. Now after 8 months she can raise her legs and her creatinine level is 2 mg/dl with normal urinating. Human umbilical cord mesenchymal stem cell implantations led to significant improvement for spinal cord entrapment and kidney failure. The major histocompatibility in allogeneic implantation is an important issue to be addressed in the future.

Tethered Spinal Cord Syndrome

MedlinePlus

... the spinal cord. These attachments cause an abnormal stretching of the spinal cord. The course of the ... the spinal cord. These attachments cause an abnormal stretching of the spinal cord. The course of the ...

Engaging cervical spinal cord networks to re-enable volitional control of hand function in tetraplegic patients

PubMed Central

Lu, Daniel C.; Edgerton, V. Reggie; Modaber, Morteza; AuYong, Nicholas; Morikawa, Erika; Zdunowski, Sharon; Sarino, Melanie E.; Nuwer, Marc R.; Roy, Roland R.; Gerasimenko, Yury

2016-01-01

Background Paralysis of the upper-limbs from spinal cord injury results in an enormous loss of independence in an individual’s daily life. Meaningful improvement in hand function is rare after one year of tetraparesis. Therapeutic developments that result in even modest gains in hand volitional function will significantly impact the quality of life for patients afflicted with high cervical injury. The ability to neuromodulate the lumbosacral spinal circuitry via epidural stimulation in regaining postural function and volitional control of the legs has been recently shown. A key question is whether a similar neuromodulatory strategy can be used to improve volitional motor control of the upper-limbs, i.e., performance of motor tasks considered to be less “automatic” than posture and locomotion. In this study, the effects of cervical epidural stimulation on hand function are characterized in subjects with chronic cervical cord injury. Objective Herein we show that epidural stimulation can be applied to the chronic injured human cervical spinal cord to promote volitional hand function. Methods and results Two subjects implanted with an cervical epidural electrode array demonstrated improved hand strength (approximately three-fold) and volitional hand control in the presence of epidural stimulation. Conclusions The present data are sufficient to suggest that hand motor function in individuals with chronic tetraplegia can be improved with cervical cord neuromodulation and thus should be comprehensively explored as a possible clinical intervention. PMID:27198185

[Functional rehabilitation of spinal cord injured persons using neuroprostheses].

PubMed

Rupp, R; Abel, R

2005-02-01

Recent technological advancements in microelectronics have led to the establishment of systems for restoration of basic functions in spinal cord injured (SCI) persons using functional electrical stimulation (FES). FES systems for the restoration of bladder and diaphragm function are well established in clinical practice. While FES systems in the lower extremities for standing/walking have not yet achieved widespread clinical acceptance, devices which enhance or restore the grasp function in tetraplegic patients with missing control of hand and fingers are demonstrably successful. Especially with the use of implantable systems a reliable, easy to handle application is possible. The most recent developments in micromechanical engineering are aimed at providing minimally invasive, subminiature systems for functional support in incomplete SCI persons. The possibility of direct brain control of FES systems will expand the application of neuroprostheses for patients with injury of the high cervical spinal cord.

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.

Hindlimb Immobilization in a Wheelchair Alters Functional Recovery Following Contusive Spinal Cord Injury in the Adult Rat

PubMed Central

Caudle, Krista L.; Brown, Edward H.; Shum-Siu, Alice; Burke, Darlene A.; Magnuson, Trystan S. G.; Voor, Michael J.; Magnuson, David S. K.

2015-01-01

Background Locomotor training of rats with thoracic contusion spinal cord injuries can induce task-specific changes in stepping but rarely results in improved overground locomotion, possibly due to a ceiling effect. Thus, the authors hypothesize that incompletely injured rats maximally retrain themselves while moving about in their cages over the first few weeks postinjury. Objective To test the hypothesis using hindlimb immobilization after mild thoracic contusion spinal cord injury in adult female rats. A passive stretch protocol was included as an independent treatment. Methods Wheelchairs were used to hold the hindlimbs stationary in an extended position leaving the forelimbs free. The wheelchairs were used for 15 to 18 hours per day, 5 days per week for 8 weeks, beginning at 4 days postinjury. A 20-minute passive hindlimb stretch therapy was applied to half of the animals. Results Hindlimb locomotor function of the wheelchair group was not different from controls at 1 week postinjury but declined significantly over the next 4 weeks. Passive stretch had no influence on wheelchair animals but limited functional recovery of normally housed animals, preventing them from regaining forelimb–hindlimb coordination. Following 8 weeks of wheelchair immobilization and stretch therapy, only the wheelchair group displayed an improvement in function when returned to normal housing but retained significant deficits in stepping and coordination out to 16 weeks. Conclusion Hindlimb immobilization and passive stretch may hinder or conceal the normal course of functional recovery of spinal cord injured rats. These observations have implications for the management of acute clinical spinal cord injuries. PMID:21697451

Childhood angular kyphosis: a plea for involvement of the pediatric neurosurgeon.

PubMed

Cornips, E; Koudijs, S; Vles, J; van Rhijn, L

2017-06-01

Childhood angular kyphosis is rare, as most children are affected by a mixed kyphotic and scoliotic deformity. Published series involving a mix of kyphosis and kyphoscoliosis, pediatric and adult, congenital and acquired cases are almost exclusively authored by orthopedic surgeons, suggesting that (pediatric) neurosurgeons are not involved. We present five cases that illustrate the spectrum of angular kyphosis, and these were treated by a multidisciplinary team including child neurologist, orthopedic surgeon, and pediatric neurosurgeon as complementary partners. Angular kyphosis is a cosmetic problem but above all a serious threat to the spinal cord and as such to the child's ambulatory, sphincter, and genito-urinary functions. Spinal cord stretch over the internal kyphosis may cause pain and/or neurological deficit, often accompanied by myelomalacia or even segmental cord atrophy. Spinal cord function may be additionally affected by associated disorders such as syringomyelia or tethered cord, an orthopedic surgeon may be less familiar with. The decision when and how to proceed surgically should be made by a multidisciplinary team, including a pediatric neurosurgeon who actively participates in the operation and helps to safely achieve adequate spinal cord decompression and stabilization. Childhood angular kyphosis is a complex, heterogeneous disorder that should be managed by a multidisciplinary team in specialized pediatric spine centers. While every case is truly unique, the spinal cord is always at risk, especially during decompression, stabilization, and eventual correction of deformity. Pediatric neurosurgeons have an important role to play in preoperative work-up, actual operation, and follow-up.

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.

Extended magnetic resonance imaging studies on the effect of classically activated microglia transplantation on white matter regeneration following spinal cord focal injury in adult rats

PubMed Central

Marcol, Wiesław; Ślusarczyk, Wojciech; Larysz-Brysz, Magdalena; Łabuzek, Krzysztof; Kapustka, Bartosz; Staszkiewicz, Rafał; Rosicka, Paulina; Kalita, Katarzyna; Węglarz, Władysław; Lewin-Kowalik, Joanna

2017-01-01

Spinal cord injuries are still a serious problem for regenerative medicine. Previous research has demonstrated that activated microglia accumulate in spinal lesions, influencing the injured tissues in various ways. Therefore, transplantation of activated microglia may have a beneficial role in the regeneration of the nervous system. The present study examined the influence of transplanted activated microglial cells in adult rats with injured spinal cords. Rats were randomly divided into an experimental (M) and control (C) group, and were subjected to non-laminectomy focal injury of spinal cord white matter by means of a high-pressured air stream. In group M, activated cultured microglial cells were injected twice into the site of injury. Functional outcome and morphological features of regeneration were analyzed during a 12-week follow-up. The lesions were characterized by means of magnetic resonance imaging (MRI). Neurons in the brain stem and motor cortex were labeled with FluoroGold (FG). A total of 12 weeks after surgery, spinal cords and brains were collected and subjected to histopathological and immunohistochemical examinations. Lesion sizes in the spinal cord were measured and the number of FG-positive neurons was counted. Rats in group M demonstrated significant improvement of locomotor performance when compared with group C (P<0.05). MRI analysis demonstrated moderate improvement in water diffusion along the spinal cord in the group M following microglia treatment, as compared with group C. The water diffusion perpendicular to the spinal cord in group M was closer to the reference values for a healthy spinal cord than it was in group C. The sizes of lesions were also significantly smaller in group M than in the group C (P<0.05). The number of brain stem and motor cortex FG-positive neurons in group M was significantly higher than in group C. The present study demonstrated that delivery of activated microglia directly into the injured spinal cord gives some positive effects for the regeneration of the white matter. PMID:29201191

The rat corticospinal system is functionally and anatomically segregated.

PubMed

Olivares-Moreno, Rafael; Moreno-Lopez, Yunuen; Concha, Luis; Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

2017-12-01

The descending corticospinal (CS) projection has been considered a key element for motor control, which results from direct and indirect modulation of spinal cord pre-motor interneurons in the intermediate gray matter of the spinal cord, which, in turn, influences motoneurons in the ventral horn. The CS tract (CST) is also involved in a selective and complex modulation of sensory information in the dorsal horn. However, little is known about the spinal network engaged by the CST and the organization of CS projections that may encode different cortical outputs to the spinal cord. This study addresses the issue of whether the CS system exerts parallel control on different spinal networks, which together participate in sensorimotor integration. Here, we show that in the adult rat, two different and partially intermingled CS neurons in the sensorimotor cortex activate, with different time latencies, distinct spinal cord neurons located in the dorsal horn and intermediate zone of the same segment. The fact that different populations of CS neurons project in a segregated manner suggests that CST is composed of subsystems controlling different spinal cord circuits that modulate motor outputs and sensory inputs in a coordinated manner.

The Effects of Intraspinal Microstimulation on Spinal Cord Tissue in the Rat

PubMed Central

Bamford, Jeremy A.; Todd, Kathryn G.; Mushahwar, Vivian K.

2010-01-01

Intraspinal microstimulation (ISMS) involves the implantation of microwires into the spinal cord below the level of an injury to excite neural networks involved in the control of locomotion in the lower limbs. The goal of this study was to examine the potential spinal cord damage that might occur with chronic ISMS. We employed functional measures of force recruitment and immunohistochemical processing of serial spinal cord sections to evaluate any damage induced by spinal transection, implantation of ISMS arrays, and electrical stimulation of 4 hours/day for 30 days. Functional measurements showed no change in force recruitment following transection and chronic ISMS, indicating no changes to underlying neural networks. The implantation of sham intraspinal microwires produced a spatially-limited increase in the density of microglia/macrophages and GFAP+ astrocytes adjacent to the microwire tracks, indicating a persistent immune response. Most importantly, these results were not different from those around microwires that were chronically pulsed with charge levels up to 48 nC/phase. Likewise, measurements of neuronal density indicated no decrease in neuronal cell bodies in the ventral grey matter surrounding ISMS microwires (243.6/mm2 ± 35.3/mm2) compared to tissue surrounding sham microwires (207.8/mm2 ± 38.8/mm2). We conclude that the implantation of intraspinal microwires and chronic application of ISMS are well tolerated by spinal cord tissue. PMID:20430436

Recovery of TES-MEPs during surgical decompression of the spine: a case series of eight patients.

PubMed

Visser, Jetze; Verra, Wiebe C; Kuijlen, Jos M; Horsting, Philip P; Journée, Henricus L

2014-12-01

This study aimed to illustrate the recovery of transcranial electrical stimulation motor evoked potentials during surgical decompression of the spinal cord in patients with impaired motor function preoperatively. Specific attention was paid to the duration of neurologic symptoms before surgery and the postoperative clinical recovery. A case series of eight patients was selected from a cohort of 74 patients that underwent spine surgery. The selected patients initially had low or absent transcranial electrical stimulation motor evoked potentials followed by a significant increase after surgical decompression of the spinal cord. A significant intraoperative increase in amplitude of motor evoked potentials was detected after decompression of the spinal cord or cauda equina in patients suffering from spinal canal stenosis (n = 2), extradural meningioma (n = 3), or a herniated nucleus polposus (n = 3). This was related to an enhanced neurologic outcome only if patients (n = 6) had a short onset (less than ½ year) of neurologic impairment before surgery. In patients with a short onset of neurologic impairment because of compression of the spinal cord or caudal fibers, an intraoperative recovery of transcranial electrical stimulation motor evoked potentials can indicate an improvement of motor function postoperatively. Therefore, transcranial electrical stimulation motor evoked potentials can be considered as a useful tool to the surgeon to monitor the quality of decompression of the spinal cord.

Measuring body structures and body functions from the International Classification of Functioning, Disability, and Health perspective: considerations for biomedical parameters in spinal cord injury research.

PubMed

Eriks-Hoogland, Inge E; Brinkhof, Martin W G; Al-Khodairy, Abdul; Baumberger, Michael; Brechbühl, Jörg; Curt, Armin; Mäder, Mark; Stucki, Gerold; Post, Marcel W M

2011-11-01

The aims of this study were to provide a selection of biomedical domains based on the comprehensive International Classification of Functioning, Disability, and Health (ICF) core sets for spinal cord injury (SCI) and to present an overview of the corresponding measurement instruments. Based on the Biomedical Domain Set, the SCI literature, the International Spinal Cord Society international data sets, and the Spinal Cord Injury Rehabilitation Evidence project publications were used to derive category specifications for use in SCI research. Expert opinion was used to derive a priority selection. The same sources were used to determine candidate measurement instruments for the specification of body functions and body structures using an example, and guiding principles were applied to select the most appropriate biomedical measurement instrument(s) for use in an SCI research project. Literature searches were performed for 41 second-level ICF body functions categories and for four second-level ICF body structures categories. For some of these categories, only a few candidate measurement instruments were found with limited variation in the type of measurement instruments. An ICF-based measurement set for biomedical aspects of functioning with SCI was established. For some categories of the ICF core sets for SCI, there is a need to develop measurement instruments.

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

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.

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

Diffusion Tensor Imaging as a Predictor of Locomotor Function after Experimental Spinal Cord Injury and Recovery

PubMed Central

Kelley, Brian J.; Harel, Noam Y.; Kim, Chang-Yeon; Papademetris, Xenophon; Coman, Daniel; Wang, Xingxing; Hasan, Omar; Kaufman, Adam; Globinsky, Ronen; Staib, Lawrence H.; Cafferty, William B.J.; Hyder, Fahmeed

2014-01-01

Abstract Traumatic spinal cord injury (SCI) causes long-term disability with limited functional recovery linked to the extent of axonal connectivity. Quantitative diffusion tensor imaging (DTI) of axonal integrity has been suggested as a potential biomarker for prognostic and therapeutic evaluation after trauma, but its correlation with functional outcomes has not been clearly defined. To examine this application, female Sprague-Dawley rats underwent midthoracic laminectomy followed by traumatic spinal cord contusion of differing severities or laminectomy without contusion. Locomotor scores and hindlimb kinematic data were collected for 4 weeks post-injury. Ex vivo DTI was then performed to assess axonal integrity using tractography and fractional anisotropy (FA), a numerical measure of relative white matter integrity, at the injury epicenter and at specific intervals rostral and caudal to the injury site. Immunohistochemistry for tissue sparing was also performed. Statistical correlation between imaging data and functional performance was assessed as the primary outcome. All injured animals showed some recovery of locomotor function, while hindlimb kinematics revealed graded deficits consistent with injury severity. Standard T2 magnetic resonance sequences illustrated conventional spinal cord morphology adjacent to contusions while corresponding FA maps indicated graded white matter pathology within these adjacent regions. Positive correlations between locomotor (Basso, Beattie, and Bresnahan score and gait kinematics) and imaging (FA values) parameters were also observed within these adjacent regions, most strongly within caudal segments beyond the lesion. Evaluation of axonal injury by DTI provides a mechanism for functional recovery assessment in a rodent SCI model. These findings suggest that focused DTI analysis of caudal spinal cord should be studied in human cases in relationship to motor outcome to augment outcome biomarkers for clinical cases. PMID:24779685

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.

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

Cervical intraspinal microstimulation evokes robust forelimb movements before and after injury

NASA Astrophysics Data System (ADS)

Sunshine, Michael D.; Cho, Frances S.; Lockwood, Danielle R.; Fechko, Amber S.; Kasten, Michael R.; Moritz, Chet T.

2013-06-01

Objective. Intraspinal microstimulation (ISMS) is a promising method for reanimating paralyzed limbs following neurological injury. ISMS within the cervical and lumbar spinal cord is capable of evoking a variety of highly-functional movements prior to injury, but the ability of ISMS to evoke forelimb movements after cervical spinal cord injury is unknown. Here we examine the forelimb movements and muscles activated by cervical ISMS both before and after contusion injury. Approach. We documented the forelimb muscles activated and movements evoked via systematic stimulation of the rodent cervical spinal cord both before injury and three, six and nine weeks following a moderate C4/C5 lateralized contusion injury. Animals were anesthetized with isoflurane to permit construction of somatotopic maps of evoked movements and quantify evoked muscle synergies between cervical segments C3 and T1. Main results. When ISMS was delivered to the cervical spinal cord, a variety of responses were observed at 68% of locations tested, with a spatial distribution that generally corresponded to the location of motor neuron pools. Stimulus currents required to achieve movement and the number of sites where movements could be evoked were unchanged by spinal cord injury. A transient shift toward extension-dominated movements and restricted muscle synergies were observed at three and six weeks following injury, respectively. By nine weeks after injury, however, ISMS-evoked patterns were similar to spinally-intact animals. Significance. The results demonstrate the potential for cervical ISMS to reanimate hand and arm function following spinal cord injury. Robust forelimb movements can be evoked both before and during the chronic stages of recovery from a clinically relevant and sustained cervical contusion injury.

Spinal Reflexes and Windup In Vitro: Effects of Analgesics and Anesthetics.

PubMed

Rivera-Arconada, Ivan; Roza, Carolina; Lopez-Garcia, Jose A

2016-02-01

The spinal cord is the first relay center for nociceptive information. Following peripheral injury, the spinal cord sensitizes. A sign of spinal sensitization is the hyper-reflexia which develops shortly after injury and can be detected in the isolated spinal cord as a "memory of pain." In this context, it is easy to understand that many analgesic compounds target spinally located sites of action to attain analgesia. In vitro isolated spinal cord preparations have been used for a number of years, and experience on the effects of compounds of diverse pharmacological families on spinal function has accumulated. Recently, we have proposed that the detailed study of spinal segmental reflexes in vitro may produce data relevant to the evaluation of the analgesic potential of novel compounds. In this review, we describe the main features of segmental reflexes obtained in vitro and discuss the effects of compounds of diverse chemical nature and pharmacological properties on such reflexes. Our aim was to compare the different profiles of action of the compounds on segmental reflexes in order to extract clues that may be helpful for pharmacological characterization of novel analgesics. © 2015 John Wiley & Sons Ltd.

Integration of donor mesenchymal stem cell-derived neuron-like cells into host neural network after rat spinal cord transection.

PubMed

Zeng, Xiang; Qiu, Xue-Cheng; Ma, Yuan-Huan; Duan, Jing-Jing; Chen, Yuan-Feng; Gu, Huai-Yu; Wang, Jun-Mei; Ling, Eng-Ang; Wu, Jin-Lang; Wu, Wutian; Zeng, Yuan-Shan

2015-06-01

Functional deficits following spinal cord injury (SCI) primarily attribute to loss of neural connectivity. We therefore tested if novel tissue engineering approaches could enable neural network repair that facilitates functional recovery after spinal cord transection (SCT). Rat bone marrow-derived mesenchymal stem cells (MSCs), genetically engineered to overexpress TrkC, receptor of neurotrophin-3 (NT-3), were pre-differentiated into cells carrying neuronal features via co-culture with NT-3 overproducing Schwann cells in 3-dimensional gelatin sponge (GS) scaffold for 14 days in vitro. Intra-GS formation of MSC assemblies emulating neural network (MSC-GS) were verified morphologically via electron microscopy (EM) and functionally by whole-cell patch clamp recording of spontaneous post-synaptic currents. The differentiated MSCs still partially maintained prototypic property with the expression of some mesodermal cytokines. MSC-GS or GS was then grafted acutely into a 2 mm-wide transection gap in the T9-T10 spinal cord segments of adult rats. Eight weeks later, hindlimb function of the MSC-GS-treated SCT rats was significantly improved relative to controls receiving the GS or lesion only as indicated by BBB score. The MSC-GS transplantation also significantly recovered cortical motor evoked potential (CMEP). Histologically, MSC-derived neuron-like cells maintained their synapse-like structures in vivo; they additionally formed similar connections with host neurites (i.e., mostly serotonergic fibers plus a few corticospinal axons; validated by double-labeled immuno-EM). Moreover, motor cortex electrical stimulation triggered c-fos expression in the grafted and lumbar spinal cord cells of the treated rats only. Our data suggest that MSC-derived neuron-like cells resulting from NT-3-TrkC-induced differentiation can partially integrate into transected spinal cord and this strategy should be further investigated for reconstructing disrupted neural circuits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Isolated cytochrome c oxidase deficiency in G93A SOD1 mice overexpressing CCS protein.

PubMed

Son, Marjatta; Leary, Scot C; Romain, Nadine; Pierrel, Fabien; Winge, Dennis R; Haller, Ronald G; Elliott, Jeffrey L

2008-05-02

G93A SOD1 transgenic mice overexpressing CCS protein develop an accelerated disease course that is associated with enhanced mitochondrial pathology and increased mitochondrial localization of mutant SOD1. Because these results suggest an effect of mutant SOD1 on mitochondrial function, we assessed the enzymatic activities of mitochondrial respiratory chain complexes in the spinal cords of CCS/G93A SOD1 and control mice. CCS/G93A SOD1 mouse spinal cord demonstrates a 55% loss of complex IV (cytochrome c oxidase) activity compared with spinal cord from age-matched non-transgenic or G93A SOD1 mice. In contrast, CCS/G93A SOD1 spinal cord shows no reduction in the activities of complex I, II, or III. Blue native gel analysis further demonstrates a marked reduction in the levels of complex IV but not of complex I, II, III, or V in spinal cords of CCS/G93A SOD1 mice compared with non-transgenic, G93A SOD1, or CCS/WT SOD1 controls. With SDS-PAGE analysis, spinal cords from CCS/G93A SOD1 mice showed significant decreases in the levels of two structural subunits of cytochrome c oxidase, COX1 and COX5b, relative to controls. In contrast, CCS/G93A SOD1 mouse spinal cord showed no reduction in levels of selected subunits from complexes I, II, III, or V. Heme A analyses of spinal cord further support the existence of cytochrome c oxidase deficiency in CCS/G93A SOD1 mice. Collectively, these results establish that CCS/G93A SOD1 mice manifest an isolated complex IV deficiency which may underlie a substantial part of mutant SOD1-induced mitochondrial cytopathy.

Agmatine Modulates the Phenotype of Macrophage Acute Phase after Spinal Cord Injury in Rats.

PubMed

Kim, Jae Hwan; Kim, Jae Young; Mun, Chin Hee; Suh, Minah; Lee, Jong Eun

2017-10-01

Agmatine is a decarboxylated arginine by arginine decarboxylase. Agmatine is known to be a neuroprotective agent. It has been reported that agmatine works as a NMDA receptor blocker or a competitive nitric oxide synthase inhibitor in CNS injuries. In spinal cord injury, agmatine showed reduction of neuropathic pain, improvement of locomotor function, and neuroprotection. Macrophage is a key cellular component in neuroinflammation, a major cause of impairment after spinal cord injury. Macrophage has subtypes, M1 and M2 macrophages. M1 macrophage induces a pro-inflammatory response, but M2 inspires an anti-inflammatory response. In this study, it was clarified whether the neuroprotective effect of agmatine is related with the modulation of macrophage subdivision after spinal cord injury. Spinal cord injury was induced in rats with contusion using MASCIS. Animals received agmatine (100 mg/kg, IP) daily for 6 days beginning the day after spinal cord injury. The proportion of M1 and M2 macrophages are confirmed with immunohistochemistry and FACS. CD206 + & ED1 + cells were counted as M2 macrophages. The systemic treatment of agmatine increased M2 macrophages caudal side to epicenter 1 week after spinal cord injury in immunohistochemistry. M2 macrophage related markers, Arginase-1 and CD206 mRNA, were increased in the agmatine treatment group and M2 macrophage expressing and stimulated cytokine, IL-10 mRNA, also was significantly overexpressed by agmatine injection. Among BMPs, BMP2/4/7, agmatine significantly increased only the expression of BMP2 known to reduce M1 macrophage under inflammatory status. These results suggest that agmatine reduces impairment after spinal cord injury through modulating the macrophage phenotype.

Agmatine Modulates the Phenotype of Macrophage Acute Phase after Spinal Cord Injury in Rats

PubMed Central

Kim, Jae Young; Mun, Chin Hee; Suh, Minah

2017-01-01

Agmatine is a decarboxylated arginine by arginine decarboxylase. Agmatine is known to be a neuroprotective agent. It has been reported that agmatine works as a NMDA receptor blocker or a competitive nitric oxide synthase inhibitor in CNS injuries. In spinal cord injury, agmatine showed reduction of neuropathic pain, improvement of locomotor function, and neuroprotection. Macrophage is a key cellular component in neuroinflammation, a major cause of impairment after spinal cord injury. Macrophage has subtypes, M1 and M2 macrophages. M1 macrophage induces a pro-inflammatory response, but M2 inspires an anti-inflammatory response. In this study, it was clarified whether the neuroprotective effect of agmatine is related with the modulation of macrophage subdivision after spinal cord injury. Spinal cord injury was induced in rats with contusion using MASCIS. Animals received agmatine (100 mg/kg, IP) daily for 6 days beginning the day after spinal cord injury. The proportion of M1 and M2 macrophages are confirmed with immunohistochemistry and FACS. CD206+ & ED1+ cells were counted as M2 macrophages. The systemic treatment of agmatine increased M2 macrophages caudal side to epicenter 1 week after spinal cord injury in immunohistochemistry. M2 macrophage related markers, Arginase-1 and CD206 mRNA, were increased in the agmatine treatment group and M2 macrophage expressing and stimulated cytokine, IL-10 mRNA, also was significantly overexpressed by agmatine injection. Among BMPs, BMP2/4/7, agmatine significantly increased only the expression of BMP2 known to reduce M1 macrophage under inflammatory status. These results suggest that agmatine reduces impairment after spinal cord injury through modulating the macrophage phenotype. PMID:29093636

Interleukin-33 treatment reduces secondary injury and improves functional recovery after contusion spinal cord injury.

PubMed

Pomeshchik, Yuriy; Kidin, Iurii; Korhonen, Paula; Savchenko, Ekaterina; Jaronen, Merja; Lehtonen, Sarka; Wojciechowski, Sara; Kanninen, Katja; Koistinaho, Jari; Malm, Tarja

2015-02-01

Interleukin-33 (IL-33) is a member of the interleukin-1 cytokine family and highly expressed in the naïve mouse brain and spinal cord. Despite the fact that IL-33 is known to be inducible by various inflammatory stimuli, its cellular localization in the central nervous system and role in pathological conditions is controversial. Administration of recombinant IL-33 has been shown to attenuate experimental autoimmune encephalomyelitis progression in one study, yet contradictory reports also exist. Here we investigated for the first time the pattern of IL-33 expression in the contused mouse spinal cord and demonstrated that after spinal cord injury (SCI) IL-33 was up-regulated and exhibited a nuclear localization predominantly in astrocytes. Importantly, we found that treatment with recombinant IL-33 alleviated secondary damage by significantly decreasing tissue loss, demyelination and astrogliosis in the contused mouse spinal cord, resulting in dramatically improved functional recovery. We identified both central and peripheral mechanisms of IL-33 action. In spinal cord, IL-33 treatment reduced the expression of pro-inflammatory tumor necrosis factor-alpha and promoted the activation of anti-inflammatory arginase-1 positive M2 microglia/macrophages, which chronically persisted in the injured spinal cord for up to at least 42 days after the treatment. In addition, IL-33 treatment showed a tendency towards reduced T-cell infiltration into the spinal cord. In the periphery, IL-33 treatment induced a shift towards the Th2 type cytokine profile and reduced the percentage and absolute number of cytotoxic, tumor necrosis factor-alpha expressing CD4+ cells in the spleen. Additionally, IL-33 treatment increased expression of T-regulatory cell marker FoxP3 and reduced expression of M1 marker iNOS in the spleen. Taken together, these results provide the first evidence that IL-33 administration is beneficial after CNS trauma. Treatment with IL33 may offer a novel therapeutic strategy for patients with acute contusion SCI. Copyright © 2014 Elsevier Inc. All rights reserved.

Functional Characterization of Lamina X Neurons in ex-Vivo Spinal Cord Preparation.

PubMed

Krotov, Volodymyr; Tokhtamysh, Anastasia; Kopach, Olga; Dromaretsky, Andrew; Sheremet, Yevhenii; Belan, Pavel; Voitenko, Nana

2017-01-01

Functional properties of lamina X neurons in the spinal cord remain unknown despite the established role of this area for somatosensory integration, visceral nociception, autonomic regulation and motoneuron output modulation. Investigations of neuronal functioning in the lamina X have been hampered by technical challenges. Here we introduce an ex-vivo spinal cord preparation with both dorsal and ventral roots still attached for functional studies of the lamina X neurons and their connectivity using an oblique LED illumination for resolved visualization of lamina X neurons in a thick tissue. With the elaborated approach, we demonstrate electrophysiological characteristics of lamina X neurons by their membrane properties, firing pattern discharge and fiber innervation (either afferent or efferent). The tissue preparation has been also probed using Ca 2+ imaging with fluorescent Ca 2+ dyes (membrane-impermeable or -permeable) to demonstrate the depolarization-induced changes in intracellular calcium concentration in lamina X neurons. Finally, we performed visualization of subpopulations of lamina X neurons stained by retrograde labeling with aminostilbamidine dye to identify sympathetic preganglionic and projection neurons in the lamina X. Thus, the elaborated approach provides a reliable tool for investigation of functional properties and connectivity in specific neuronal subpopulations, boosting research of lamina X of the spinal cord.

Scissors stab wound to the cervical spinal cord at the craniocervical junction.

PubMed

Zhang, Xiao-Yong; Yang, Ying-Ming

2016-06-01

Stab wounds resulting in spinal cord injury of the craniocervical junction are rare. A scissors stab wound to the cervical spinal cord has been reported only once in the literature. This paper aimed to report a case of Brown-Séquard-plus syndrome in an 8-year-old boy secondary to a scissors stab wound at the craniocervical junction. Case report and review of the literature. Case report of an 8-year-old boy accidentally stabbed in the neck by scissors, which were thrown as a dart. The case study of an 8-year-old boy who was hospitalized because of a scissors stab wound at the craniocervical junction. The patient developed Brown-Séquard-plus syndrome on the left side of the body. Magnetic resonance imaging revealed a laceration of the spinal cord at the craniocervical junction with cerebrospinal fluid leakage. Careful cleansing and interrupted sutures of the wounds were performed to prevent cerebrospinal fluid leakage. Rehabilitation therapy was performed 2 days later. A follow-up examination revealed complete recovery of the neurologic deficit 8 months post-injury. Treatment of scissors stab wounds to the cervical spinal cord, whether conservative management or thorough surgical exploration, should be individualized based on history, examination, and imaging. As shown in this case report, despite conservative management, complete recovery, which was unexpected, was attributed to the initial mild laceration of the spinal cord and ipsilateral spinal cord functional compensation. Copyright © 2016 Elsevier Inc. All rights reserved.

Spinal Cord Gray Matter Atrophy in Amyotrophic Lateral Sclerosis.

PubMed

Paquin, M-Ê; El Mendili, M M; Gros, C; Dupont, S M; Cohen-Adad, J; Pradat, P-F

2018-01-01

There is an emerging need for biomarkers to better categorize clinical phenotypes and predict progression in amyotrophic lateral sclerosis. This study aimed to quantify cervical spinal gray matter atrophy in amyotrophic lateral sclerosis and investigate its association with clinical disability at baseline and after 1 year. Twenty-nine patients with amyotrophic lateral sclerosis and 22 healthy controls were scanned with 3T MR imaging. Standard functional scale was recorded at the time of MR imaging and after 1 year. MR imaging data were processed automatically to measure the spinal cord, gray matter, and white matter cross-sectional areas. A statistical analysis assessed the difference in cross-sectional areas between patients with amyotrophic lateral sclerosis and controls, correlations between spinal cord and gray matter atrophy to clinical disability at baseline and at 1 year, and prediction of clinical disability at 1 year. Gray matter atrophy was more sensitive to discriminate patients with amyotrophic lateral sclerosis from controls ( P = .004) compared with spinal cord atrophy ( P = .02). Gray matter and spinal cord cross-sectional areas showed good correlations with clinical scores at baseline ( R = 0.56 for gray matter and R = 0.55 for spinal cord; P < .01). Prediction at 1 year with clinical scores ( R 2 = 0.54) was improved when including a combination of gray matter and white matter cross-sectional areas ( R 2 = 0.74). Although improvements over spinal cord cross-sectional areas were modest, this study suggests the potential use of gray matter cross-sectional areas as an MR imaging structural biomarker to monitor the evolution of amyotrophic lateral sclerosis. © 2018 by American Journal of Neuroradiology.

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

Where and When to Cut? Fluorescein Guidance for Brain Stem and Spinal Cord Tumor Surgery-Technical Note.

PubMed

Molina, Eric Suero; Stummer, Walter

2017-12-29

Spinal cord and brain stem lesions require a judicious approach with an optimized trajectory due to a clustering of functions on their surfaces. Intraoperative mapping helps locate function. To confidently locate such lesions, neuronavigation alone lacks the desired accuracy and is of limited use in the spinal cord. To evaluate the clinical value of fluoresceins for initial delineation of such critically located lesions. We evaluated fluorescein guidance in the surgical resection of lesions with blood-brain barrier disruption demonstrating contrast enhancement in magnet resonance imaging in the spinal cord and in the brain stem in 3 different patients. Two patients harbored a diffuse cervical and thoracic spinal cord lesion, respectively. Another patient suffered metastatic lesions in the brain stem and at the floor of the fourth ventricle. Low-dose fluorescein (4 mg/kg body weight) was applied after anesthesia induction and visualized using the Zeiss Pentero 900 Yellow560 filter (Carl Zeiss, Oberkochen, Germany). Fluorescein was helpful for locating lesions and for defining the best possible trajectory. During resection, however, we found unspecific propagation of fluorescein within the brain stem up to 6 mm within 3 h after application. As these lesions were otherwise distinguishable from surrounding tissue, monitoring resection was not an issue. Fluorescein guidance is a feasible tool for defining surgical entry zones when aiming for surgical removal of spinal cord and brain stem lesions. Unselective fluorescein extravasation cautions against using such methodology for monitoring completeness of resection. Providing the right timing, a window of pseudoselectivity could increase fluoresceins' clinical value in these cases. © Congress of Neurological Surgeons 2017.

Adenovirus vector-mediated ex vivo gene transfer of brain-derived neurotrophic factor to bone marrow stromal cells promotes axonal regeneration after transplantation in completely transected adult rat spinal cord

PubMed Central

Kamada, Takahito; Hashimoto, Masayuki; Murakami, Masazumi; Shirasawa, Hiroshi; Sakao, Seiichiro; Ino, Hidetoshi; Yoshinaga, Katsunori; Koshizuka, Shuhei; Moriya, Hideshige; Yamazaki, Masashi

2007-01-01

The aim of this study was to evaluate the efficacy in adult rat completely transected spinal cord of adenovirus vector-mediated brain-derived neurotrophic factor (BDNF) ex vivo gene transfer to bone marrow stromal cells (BMSC). BMSC were infected with adenovirus vectors carrying β-galactosidase (AxCALacZ) or BDNF (AxCABDNF) genes. The T8 segment of spinal cord was removed and replaced by graft containing Matrigel alone (MG group) or Matrigel and BMSC infected by AxCALacZ (BMSC-LacZ group) or AxCABDNF (BMSC-BDNF group). Axons in the graft were evaluated by immunohistochemistry and functional recovery was assessed with BBB locomotor scale. In the BMSC-BDNF group, the number of fibers positive for growth associated protein-43, tyrosine hydroxylase, and calcitonin gene-related peptide was significantly larger than numbers found for the MG and BMSC-LacZ groups. Rats from BMSC-BDNF and BMSC-LacZ groups showed significant recovery of hind limb function compared with MG rats; however, there was no significant difference between groups in degree of functional recovery. These findings demonstrate that adenovirus vector-mediated ex vivo gene transfer of BDNF enhances the capacity of BMSC to promote axonal regeneration in this completely transected spinal cord model; however, BDNF failed to enhance hind limb functional recovery. Further investigation is needed to establish an optimal combination of cell therapy and neurotrophin gene transfer for cases of spinal cord injury. PMID:17885772

Sexual Counseling with Spinal Cord-Injured Clients

ERIC Educational Resources Information Center

Miller, Donald K.

1975-01-01

Spinal cord-injured clients have many fears and misapprehensions about their sexual functioning. Such misapprehensions can be helped by the counselor's willingness to discuss sexual issues openly. Clients need a clear and accurate picture of the facts, as well as encouragement and support to help them rediscover their sexuality. (Author)

Biodegradable Spheres Protect Traumatically Injured Spinal Cord by Alleviating the Glutamate-Induced Excitotoxicity.

PubMed

Liu, Dongfei; Chen, Jian; Jiang, Tao; Li, Wei; Huang, Yao; Lu, Xiyi; Liu, Zehua; Zhang, Weixia; Zhou, Zheng; Ding, Qirui; Santos, Hélder A; Yin, Guoyong; Fan, Jin

2018-04-01

New treatment strategies for spinal cord injury with good therapeutic efficacy are actively pursued. Here, acetalated dextran (AcDX), a biodegradable polymer obtained by modifying vicinal diols of dextran, is demonstrated to protect the traumatically injured spinal cord. To facilitate its administration, AcDX is formulated into microspheres (≈7.2 µm in diameter) by the droplet microfluidic technique. Intrathecally injected AcDX microspheres effectively reduce the traumatic lesion volume and inflammatory response in the injured spinal cord, protect the spinal cord neurons from apoptosis, and ultimately, recover the locomotor function of injured rats. The neuroprotective feature of AcDX microspheres is achieved by sequestering glutamate and calcium ions in cerebrospinal fluid. The scavenging of glutamate and calcium ion reduces the influx of calcium ions into neurons and inhibits the formation of reactive oxygen species. Consequently, AcDX microspheres attenuate the expression of proapoptotic proteins, Calpain, and Bax, and enhance the expression of antiapoptotic protein Bcl-2. Overall, AcDX microspheres protect traumatically injured spinal cord by alleviating the glutamate-induced excitotoxicity. This study opens an exciting perspective toward the application of neuroprotective AcDX for the treatment of severe neurological diseases. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Relative shortening and functional tethering of spinal cord in adolescent scoliosis - Result of asynchronous neuro-osseous growth, summary of an electronic focus group debate of the IBSE.

PubMed

Chu, Winnie Cw; Lam, Wynnie Mw; Ng, Bobby Kw; Tze-Ping, Lam; Lee, Kwong-Man; Guo, Xia; Cheng, Jack Cy; Burwell, R Geoffrey; Dangerfield, Peter H; Jaspan, Tim

2008-06-27

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The Statement for this debate was written by Dr WCW Chu and colleagues who examine the spinal cord to vertebral growth interaction during adolescence in scoliosis. Using the multi-planar reconstruction technique of magnetic resonance imaging they investigated the relative length of spinal cord to vertebral column including ratios in 28 girls with AIS (mainly thoracic or double major curves) and 14 age-matched normal girls. Also evaluated were cerebellar tonsillar position, somatosensory evoked potentials (SSEPs), and clinical neurological examination. In severe AIS compared with normal controls, the vertebral column is significantly longer without detectable spinal cord lengthening. They speculate that anterior spinal column overgrowth relative to a normal length spinal cord exerts a stretching tethering force between the two ends, cranially and caudally leading to the initiation and progression of thoracic AIS. They support and develop the Roth-Porter concept of uncoupled neuro-osseous growth in the pathogenesis of AIS which now they prefer to term 'asynchronous neuro-osseous growth'. Morphological evidence about the curve apex suggests that the spinal cord is also affected, and a 'double pathology' is suggested. AIS is viewed as a disorder with a wide spectrum and a common neuroanatomical abnormality namely, a spinal cord of normal length but short relative to an abnormally lengthened anterior vertebral column. Neuroanatomical changes and/or abnormal neural function may be expressed only in severe cases. This asynchronous neuro-osseous growth concept is regarded as one component of a larger concept. The other component relates to the brain and cranium of AIS subjects because abnormalities have been found in brain (infratentorial and supratentorial) and skull (vault and base). The possible relevance of systemic melatonin-signaling pathway dysfunction, platelet calmodulin levels and putative vertebral vascular biology to the asynchronous neuro-osseous growth concept is discussed. A biomechanical model to test the spinal component of the concept is in hand. There is no published research on the biomechanical properties of the spinal cord for scoliosis specimens. Such research on normal spinal cords includes movements (kinematics), stress-strain responses to uniaxial loading, and anterior forces created by the stretched cord in forward flexion that may alter sagittal spinal shape during adolescent growth. The asynchronous neuro-osseous growth concept for the spine evokes controversy. Dr Chu and colleagues respond to five other concepts of pathogenesis for AIS and suggest that relative anterior spinal overgrowth and biomechanical growth modulation may also contribute to AIS pathogenesis.

Sexual Functioning in Men Living with a Spinal Cord Injury–A Narrative Literature Review

PubMed Central

Sunilkumar, MM; Boston, Patricia; Rajagopal, MR

2015-01-01

Background: Sexual dysfunction is a major concern for Indian men living with a spinal cord injury Objectives: To examine the literature related to sexuality traumatic cord injury and its impact on sexual functioning. Materials and Methods: Databases using Cumulative Index to Nursing and Allied Health Literature (CINAHL) 2000–2012, Medline 1989–2012, Applied Social Sciences Index and Abstracts (ASSIA) 1989–2012 and Google Scholar were the search engines used used for literature review. Results: The search yielded a total of 457 articles and only 75 of them were found relevant. The minimum number of articles required to meet the inclusion criteria for this review was 25–30 articles. Out of the 75 articles, 33 were considered relevant or related to the topic of sexual functioning, spinal cord injury, and paraplegia. Six areas were identified: Sexual stigmatization, physiological barriers to sexual satisfaction, clinical aspects of sexual functioning, biomedical approaches to sexual dysfunction, partner satisfaction, and lack of accessibility to sexual education. Conclusion: Spinal cord injury and sexual functioning affects a large segment of the male Indian population, yet most current research focuses on quantitative measurement with the emphasis on ejaculatory dysfunction, orgasm impairment, incontinence, and other physiological dysfunction. Further research is needed to address the subjective accounts of patients themselves with respect to the emotional and social impact of sexual disability. This would help to identify the best possible outcomes for both treatment and rehabilitation. PMID:26600694

Agmatine improves locomotor function and reduces tissue damage following spinal cord injury.

PubMed

Yu, C G; Marcillo, A E; Fairbanks, C A; Wilcox, G L; Yezierski, R P

2000-09-28

Clinically effective drug treatments for spinal cord injury (SCI) remain unavailable. Agmatine, an NMDA receptor antagonist and inhibitor of nitric oxide synthase (NOS), is an endogenous neuromodulator found in the brain and spinal cord. Evidence is presented that agmatine significantly improves locomotor function and reduces tissue damage following traumatic SCI in rats. The results suggest the importance of future therapeutic strategies encompassing the use of single drugs with multiple targets for the treatment of acute SCI. The therapeutic targets of agmatine (NMDA receptor and NOS) have been shown to be critically linked to the pathophysiological sequelae of CNS injury and this, combined with the non-toxic profile, lends support to agmatine being considered as a potential candidate for future clinical applications.

Human dental pulp stem cells transplantation combined with treadmill training in rats after traumatic spinal cord injury

PubMed Central

Nicola, F.C.; Rodrigues, L.P.; Crestani, T.; Quintiliano, K.; Sanches, E.F.; Willborn, S.; Aristimunha, D.; Boisserand, L.; Pranke, P.; Netto, C.A.

2016-01-01

Spinal cord injury (SCI) is a disabling condition resulting in deficits of sensory and motor functions, and has no effective treatment. Considering that protocols with stem cell transplantation and treadmill training have shown promising results, the present study evaluated the effectiveness of stem cells from human exfoliated deciduous teeth (SHEDs) transplantation combined with treadmill training in rats with experimental spinal cord injury. Fifty-four Wistar rats were spinalized using NYU impactor. The rats were randomly distributed into 5 groups: Sham (laminectomy with no SCI, n=10); SCI (laminectomy followed by SCI, n=12); SHEDs (SCI treated with SHEDs, n=11); TT (SCI treated with treadmill training, n=11); SHEDs+TT (SCI treated with SHEDs and treadmill training; n=10). Treatment with SHEDs alone or in combination with treadmill training promoted functional recovery, reaching scores of 15 and 14, respectively, in the BBB scale, being different from the SCI group, which reached 11. SHEDs treatment was able to reduce the cystic cavity area and glial scar, increase neurofilament. Treadmill training alone had no functional effectiveness or tissue effects. In a second experiment, the SHEDs transplantation reduced the TNF-α levels in the cord tissue measured 6 h after the injury. Contrary to our hypothesis, treadmill training either alone or in combination, caused no functional improvement. However, SHEDs showed to be neuroprotective, by the reduction of TNF-α levels, the cystic cavity and the glial scar associated with the improvement of motor function after SCI. These results provide evidence that grafted SHEDs might be an effective therapy to spinal cord lesions, with possible anti-inflammatory action. PMID:27509306

Human dental pulp stem cells transplantation combined with treadmill training in rats after traumatic spinal cord injury.

PubMed

Nicola, F C; Rodrigues, L P; Crestani, T; Quintiliano, K; Sanches, E F; Willborn, S; Aristimunha, D; Boisserand, L; Pranke, P; Netto, C A

2016-08-08

Spinal cord injury (SCI) is a disabling condition resulting in deficits of sensory and motor functions, and has no effective treatment. Considering that protocols with stem cell transplantation and treadmill training have shown promising results, the present study evaluated the effectiveness of stem cells from human exfoliated deciduous teeth (SHEDs) transplantation combined with treadmill training in rats with experimental spinal cord injury. Fifty-four Wistar rats were spinalized using NYU impactor. The rats were randomly distributed into 5 groups: Sham (laminectomy with no SCI, n=10); SCI (laminectomy followed by SCI, n=12); SHEDs (SCI treated with SHEDs, n=11); TT (SCI treated with treadmill training, n=11); SHEDs+TT (SCI treated with SHEDs and treadmill training; n=10). Treatment with SHEDs alone or in combination with treadmill training promoted functional recovery, reaching scores of 15 and 14, respectively, in the BBB scale, being different from the SCI group, which reached 11. SHEDs treatment was able to reduce the cystic cavity area and glial scar, increase neurofilament. Treadmill training alone had no functional effectiveness or tissue effects. In a second experiment, the SHEDs transplantation reduced the TNF-α levels in the cord tissue measured 6 h after the injury. Contrary to our hypothesis, treadmill training either alone or in combination, caused no functional improvement. However, SHEDs showed to be neuroprotective, by the reduction of TNF-α levels, the cystic cavity and the glial scar associated with the improvement of motor function after SCI. These results provide evidence that grafted SHEDs might be an effective therapy to spinal cord lesions, with possible anti-inflammatory action.

Suspension Matrices for Improved Schwann-Cell Survival after Implantation into the Injured Rat Spinal Cord

PubMed Central

Patel, Vivek; Joseph, Gravil; Patel, Amit; Patel, Samik; Bustin, Devin; Mawson, David; Tuesta, Luis M.; Puentes, Rocio; Ghosh, Mousumi

2010-01-01

Abstract Trauma to the spinal cord produces endogenously irreversible tissue and functional loss, requiring the application of therapeutic approaches to achieve meaningful restoration. Cellular strategies, in particular Schwann-cell implantation, have shown promise in overcoming many of the obstacles facing successful repair of the injured spinal cord. Here, we show that the implantation of Schwann cells as cell suspensions with in-situ gelling laminin:collagen matrices after spinal-cord contusion significantly enhances long-term cell survival but not proliferation, as well as improves graft vascularization and the degree of axonal in-growth over the standard implantation vehicle, minimal media. The use of a matrix to suspend cells prior to implantation should be an important consideration for achieving improved survival and effectiveness of cellular therapies for future clinical application. PMID:20144012

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.

N-methyl-D-aspartate receptor antagonist MK-801 prevents apoptosis in rats that have undergone fetal spinal cord transplantation following spinal hemisection.

PubMed

Zhang, Qiang; Shao, Yang; Zhao, Changsong; Cai, Juan; Sun, Sheng

2014-12-01

Spinal cord injury is the main cause of paraplegia, but effective therapies for it are lacking. Embryonic spinal cord transplantation is able to repair spinal cord injury, albeit with a large amount of neuronal apoptosis remaining in the spinal cord. MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, is able to reduce cell death by decreasing the concentration of excitatory amino acids and preventing extracellular calcium ion influx. In this study, the effect of MK-801 on the apoptosis of spinal cord neurons in rats that have received a fetal spinal cord (FSC) transplant following spinal hemisection was investigated. Wistar rats were divided into three groups: Spinal cord hemisection injury with a combination of FSC transplantation and MK-801 treatment (group A); spinal cord hemisection injury with FSC transplantation (group B); and spinal cord injury with insertion of a Gelfoam pledget (group C). The rats were sacrificed 1, 3, 7 and 14 days after the surgery. Apoptosis in spinal slices from the injured spinal cord was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling reaction, and the expression of B-cell lymphoma-2 (Bcl-2) was measured by immunohistochemistry. The positive cells were quantitatively analyzed using a computer image analysis system. The rate of apoptosis and the positive expression of Bcl-2 protein in the spinal cord neurons in the three groups decreased in the following order: C>B>A (P<0.05) and A>B>C (P<0.05), respectively. This indicates that treatment with the NMDA receptor antagonist MK-801 prevents apoptosis in the spinal cord neurons of rats that have undergone FSC transplantation following spinal hemisection.

N-methyl-D-aspartate receptor antagonist MK-801 prevents apoptosis in rats that have undergone fetal spinal cord transplantation following spinal hemisection

PubMed Central

ZHANG, QIANG; SHAO, YANG; ZHAO, CHANGSONG; CAI, JUAN; SUN, SHENG

2014-01-01

Spinal cord injury is the main cause of paraplegia, but effective therapies for it are lacking. Embryonic spinal cord transplantation is able to repair spinal cord injury, albeit with a large amount of neuronal apoptosis remaining in the spinal cord. MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, is able to reduce cell death by decreasing the concentration of excitatory amino acids and preventing extracellular calcium ion influx. In this study, the effect of MK-801 on the apoptosis of spinal cord neurons in rats that have received a fetal spinal cord (FSC) transplant following spinal hemisection was investigated. Wistar rats were divided into three groups: Spinal cord hemisection injury with a combination of FSC transplantation and MK-801 treatment (group A); spinal cord hemisection injury with FSC transplantation (group B); and spinal cord injury with insertion of a Gelfoam pledget (group C). The rats were sacrificed 1, 3, 7 and 14 days after the surgery. Apoptosis in spinal slices from the injured spinal cord was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling reaction, and the expression of B-cell lymphoma-2 (Bcl-2) was measured by immunohistochemistry. The positive cells were quantitatively analyzed using a computer image analysis system. The rate of apoptosis and the positive expression of Bcl-2 protein in the spinal cord neurons in the three groups decreased in the following order: C>B>A (P<0.05) and A>B>C (P<0.05), respectively. This indicates that treatment with the NMDA receptor antagonist MK-801 prevents apoptosis in the spinal cord neurons of rats that have undergone FSC transplantation following spinal hemisection. PMID:25371724

Rapamycin suppresses microglial activation and reduces the development of neuropathic pain after spinal cord injury.

PubMed

Tateda, Satoshi; Kanno, Haruo; Ozawa, Hiroshi; Sekiguchi, Akira; Yahata, Kenichiro; Yamaya, Seiji; Itoi, Eiji

2017-01-01

Rapamycin is an inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway, plays an important role in multiple cellular functions. Our previous study showed rapamycin treatment in acute phase reduced the neural tissue damage and locomotor impairment after spinal cord injury (SCI). However, there has been no study to investigate the therapeutic effect of rapamycin on neuropathic pain after SCI. In this study, we examined whether rapamycin reduces neuropathic pain following SCI in mice. We used a mouse model of thoracic spinal cord contusion injury, and divided the mice into the rapamycin-treated and the vehicle-treated groups. The rapamycin-treated mice were intraperitoneally injected with rapamycin (1 mg/kg) 4 h after SCI. The rapamycin treatment suppressed phosphorylated-p70S6K in the injured spinal cord that indicated inhibition of mTOR. The rapamycin treatment significantly improved not only locomotor function, but also mechanical and thermal hypersensitivity in the hindpaws after SCI. In an immunohistochemical analysis, Iba-1-stained microglia in the lumbar spinal cord was significantly decreased in the rapamycin-treated mice. In addition, the activity of p38 MAPK in the lumbar spinal cord was significantly attenuated by rapamycin treatment. Furthermore, phosphorylated-p38 MAPK-positive microglia was relatively decreased in the rapamycin-treated mice. These results indicated rapamycin administration in acute phase to reduce secondary neural tissue damage can contribute to the suppression of the microglial activation in the lumbar spinal cord and attenuate the development of neuropathic pain after SCI. The present study first demonstrated that rapamycin has significant therapeutic potential to reduce the development of neuropathic pain following SCI. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:93-103, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Mechanisms of motor recovery after subtotal spinal cord injury: insights from the study of mice carrying a mutation (WldS) that delays cellular responses to injury.

PubMed

Zhang, Z; Guth, L; Steward, O

1998-01-01

Partial lesions of the mammalian spinal cord result in an immediate motor impairment that recovers gradually over time; however, the cellular mechanisms responsible for the transient nature of this paralysis have not been defined. A unique opportunity to identify those injury-induced cellular responses that mediate the recovery of function has arisen from the discovery of a unique mutant strain of mice in which the onset of Wallerian degeneration is dramatically delayed. In this strain of mice (designated WldS for Wallerian degeneration, slow), many of the cellular responses to spinal cord injury are also delayed. We have used this experimental animal model to evaluate possible causal relationships between these delayed cellular responses and the onset of functional recovery. For this purpose, we have compared the time course of locomotor recovery in C57BL/6 (control) mice and in WldS (mutant) mice by hemisecting the spinal cord at T8 and evaluating locomotor function at daily postoperative intervals. The time course of locomotor recovery (as determined by the Tarlov open-field walking procedure) was substantially delayed in mice carrying the WldS mutation: C57BL/6 control mice began to stand and walk within 6 days (mean Tarlov score of 4), whereas mutant mice did not exhibit comparable locomotor function until 16 days postoperatively. (a) The rapid return of locomotor function in the C57BL/6 mice suggests that the recovery resulted from processes of functional plasticity rather than from regeneration or collateral sprouting of nerve fibers. (b) The marked delay in the return of locomotor function in WldS mice indicates that the processes of neuroplasticity are induced by degenerative changes in the damaged neurons. (c) These strains of mice can be effectively used in future studies to elucidate the specific biochemical and physiological alterations responsible for inducing functional plasticity and restoring locomotor function after spinal cord injury.

Assessing denoising strategies to increase signal to noise ratio in spinal cord and in brain cortical and subcortical regions

NASA Astrophysics Data System (ADS)

Maugeri, L.; Moraschi, M.; Summers, P.; Favilla, S.; Mascali, D.; Cedola, A.; Porro, C. A.; Giove, F.; Fratini, M.

2018-02-01

Functional Magnetic Resonance Imaging (fMRI) based on Blood Oxygenation Level Dependent (BOLD) contrast has become one of the most powerful tools in neuroscience research. On the other hand, fMRI approaches have seen limited use in the study of spinal cord and subcortical brain regions (such as the brainstem and portions of the diencephalon). Indeed obtaining good BOLD signal in these areas still represents a technical and scientific challenge, due to poor control of physiological noise and to a limited overall quality of the functional series. A solution can be found in the combination of optimized experimental procedures at acquisition stage, and well-adapted artifact mitigation procedures in the data processing. In this framework, we studied two different data processing strategies to reduce physiological noise in cortical and subcortical brain regions and in the spinal cord, based on the aCompCor and RETROICOR denoising tools respectively. The study, performed in healthy subjects, was carried out using an ad hoc isometric motor task. We observed an increased signal to noise ratio in the denoised functional time series in the spinal cord and in the subcortical brain region.

21 CFR 882.5880 - Implanted spinal cord stimulator for pain relief.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Implanted spinal cord stimulator for pain relief. (a) Identification. An implanted spinal cord stimulator for pain relief is a device that is used to stimulate electrically a patient's spinal cord to relieve... on the patient's spinal cord and an external transmitter for transmitting the stimulating pulses...

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.

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…

The human natural killer-1 (HNK-1) glycan mimetic ursolic acid promotes functional recovery after spinal cord injury in mouse.

PubMed

Sahu, Sudhanshu; Li, Rong; Kadeyala, Praveen Kumar; Liu, Shisong; Schachner, Melitta

2018-05-01

Human natural killer-1 (HNK-1) cell antigen is a glycan epitope involved in several neural events, such as neuritogenesis, myelination, synaptic plasticity and regeneration of the nervous system after injury. We have recently identified the small organic compound ursolic acid (UA) as a HNK-1 mimetic with the aim to test its therapeutic potential in the central nervous system. UA, a plant-derived pentacyclic triterpenoid, is well known for its multiple biological functions, including neuroprotective, antioxidant and anti-inflammatory activities. In the present study, we evaluated its functions in a mouse model of spinal cord injury (SCI) and explored the molecular mechanisms underlying its positive effects. Oral administration of UA to mice 1 h after SCI and thereafter once daily for 6 weeks enhanced the regaining of motor functions and axonal regrowth, and decreased astrogliosis. UA administration decreased levels of proinflammatory markers, including interleukin-6 and tumor necrosis factor-α, in the injured spinal cord at the acute phase of inflammation and activated the mitogen-activated protein kinase and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways in the injured spinal cord. Taken together, these results suggest that UA may be a candidate for treatment of nervous system injuries. Copyright © 2017. Published by Elsevier Inc.

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

Effects of polarization in low-level laser therapy of spinal cord injury in rats

NASA Astrophysics Data System (ADS)

Ando, Takahiro; Sato, Shunichi; Kobayashi, Hiroaki; Nawashiro, Hiroshi; Ashida, Hiroshi; Hamblin, Michael R.; Obara, Minoru

2012-03-01

Low-level laser therapy (LLLT) is a promising approach to treat the spinal cord injury (SCI). Since nerve fibers have optical anisotropy, propagation of light in the spinal tissue might be affected by its polarization direction. However, the effect of polarization on the efficacy of LLLT has not been elucidated. In the present study, we investigated the effect of polarization on the efficacy of near-infrared LLLT for SCI. Rat spinal cord was injured with a weight-drop device. The lesion site was irradiated with an 808-nm diode laser beam that was transmitted through a polarizing filter immediately after injury and daily for five consecutive days. The laser power at the injured spinal cord surface was 25 mW, and the dosage per day was 9.6 J/cm2 (spot diameter, 2 cm; irradiation duration, 1200 s). Functional recovery was assessed daily by an open-field test. The results showed that the functional scores of the SCI rats that were treated with 808-nm laser irradiation were significantly higher than those of the SCI alone group (Group 1) from day 5 after injury, regardless of the polarization direction. Importantly, as compared to the locomotive function of the SCI rats that were treated with the perpendicularly-polarized laser parallel to the spinal column (Group 2), that of the SCI rats that were irradiated with the linearly aligned polarization (Group 3) was significantly improved from day 10 after injury. In addition, the ATP contents in the injured spinal tissue of Group 3, which were measured immediately after laser irradiation, were moderately higher than those of Group 2. These observations are attributable to the deeper penetration of the parallelpolarized light in the anisotropic spinal tissue, suggesting that polarization direction significantly affects the efficacy of LLLT for SCI.

Targeted, activity-dependent spinal stimulation produces long-lasting motor recovery in chronic cervical spinal cord injury

PubMed Central

McPherson, Jacob G.; Miller, Robert R.; Perlmutter, Steve I.

2015-01-01

Use-dependent movement therapies can lead to partial recovery of motor function after neurological injury. We attempted to improve recovery by developing a neuroprosthetic intervention that enhances movement therapy by directing spike timing-dependent plasticity in spared motor pathways. Using a recurrent neural–computer interface in rats with a cervical contusion of the spinal cord, we synchronized intraspinal microstimulation below the injury with the arrival of functionally related volitional motor commands signaled by muscle activity in the impaired forelimb. Stimulation was delivered during physical retraining of a forelimb behavior and throughout the day for 3 mo. Rats receiving this targeted, activity-dependent spinal stimulation (TADSS) exhibited markedly enhanced recovery compared with animals receiving targeted but open-loop spinal stimulation and rats receiving physical retraining alone. On a forelimb reach and grasp task, TADSS animals recovered 63% of their preinjury ability, more than two times the performance level achieved by the other therapy groups. Therapeutic gains were maintained for 3 additional wk without stimulation. The results suggest that activity-dependent spinal stimulation can induce neural plasticity that improves behavioral recovery after spinal cord injury. PMID:26371306

Activity-Based Restorative Therapies: Concepts and Applications in Spinal Cord Injury-Related Neurorehabilitation

ERIC Educational Resources Information Center

Sadowsky, Cristina L.; McDonald, John W.

2009-01-01

Physical rehabilitation following spinal cord injury-related paralysis has traditionally focused on teaching compensatory techniques, thus enabling the individual to achieve day-to-day function despite significant neurological deficits. But the concept of an irreparable central nervous system (CNS) is slowly being replaced with evidence related to…

Development of a universal measure of quadrupedal forelimb-hindlimb coordination using digital motion capture and computerised analysis.

PubMed

Hamilton, Lindsay; Franklin, Robin J M; Jeffery, Nick D

2007-09-18

Clinical spinal cord injury in domestic dogs provides a model population in which to test the efficacy of putative therapeutic interventions for human spinal cord injury. To achieve this potential a robust method of functional analysis is required so that statistical comparison of numerical data derived from treated and control animals can be achieved. In this study we describe the use of digital motion capture equipment combined with mathematical analysis to derive a simple quantitative parameter - 'the mean diagonal coupling interval' - to describe coordination between forelimb and hindlimb movement. In normal dogs this parameter is independent of size, conformation, speed of walking or gait pattern. We show here that mean diagonal coupling interval is highly sensitive to alterations in forelimb-hindlimb coordination in dogs that have suffered spinal cord injury, and can be accurately quantified, but is unaffected by orthopaedic perturbations of gait. Mean diagonal coupling interval is an easily derived, highly robust measurement that provides an ideal method to compare the functional effect of therapeutic interventions after spinal cord injury in quadrupeds.

Psychological well-being after spinal cord injury: perception of loss and meaning making.

PubMed

deRoon-Cassini, Terri A; de St Aubin, Ed; Valvano, Abbey; Hastings, James; Horn, Patricia

2009-08-01

This study examined the influence of medical injury severity, perceived loss of physical functioning (conceptualized as physical resource loss), and global meaning making on psychological well-being among 79 veterans living with a spinal cord injury. Structured interviews were completed to assess perceived loss of physical abilities using the Conservation of Resources-Evaluation and SF-36 Health Survey, global meaning making (Purpose in Life scale), and psychological well-being (Sense of Well-Being Inventory). Medical injury severity was calculated from medical records. Medical injury severity was not related to psychological well-being, whereas perceived loss of physical functioning was inversely associated. Global meaning making was significantly related to and accounted for a large portion of the variance in psychological well-being. Results suggest that global meaning making partially mediates perceived loss of physical resources and psychological well-being. The perceived loss of physical abilities and the generation of meaning and purpose in life are important variables that relate to positive adaptation following spinal cord injury. Treatment implications related to factors that increase quality of life following spinal cord injury are discussed. (c) 2009 APA

Recovery of sensorimotor function and activities of daily living after cervical spinal cord injury: the influence of age.

PubMed

Wirz, Markus; Dietz, Volker

2015-02-01

This retrospective study was designed to examine the influence of age on the outcome of motor function and activities of daily living (ADLs) in patients with a cervical spinal cord injury (SCI). The study is based on the data registry of the European Multicenter Study of Spinal Cord Injury (EMSCI) study group. Initial upper-extremity motor score (UEMS) and its change over 5 months, as well as the initial Spinal Cord Independence Measure (SCIM) score, did not differ between younger adults (20-39 years) and elderly (60-79 years) patients. However, the change in SCIM score over 5 months was significantly greater in the younger patient group. Initial UEMS, SCIM, and ulnar compound motor action potentials (CMAP), reflecting peripheral nerve damage (motoneurons and roots), were significantly greater in incomplete, compared to complete, SCI, regardless of age group. The initial assessment of UEMS in combination with CMAP recordings allows an early prediction of ADLs outcomes in both younger adults and elderly subjects. The impaired translation of gain in motor score into increased ADL independence in elderly patients requires specifically tailored rehabilitation programs.

Clinical Trials Network / Building Infrastructure to Accelerate Transfer of Basic Research in Spinal Cord Injury (SCI) to Clinical Practice

DTIC Science & Technology

2015-05-01

Glasgow Coma Scale (GCS) and of associated injuries with the Abbreviated Injury Scale . The American Spinal Injury Association impairment scale (AIS) is...registry protocol includes: the AIS Impairment Scale , and where appropriate, the Functional Independence Measure FIM™, the Spinal Cord Independence...have been achieved with the registry. Enrollment of 762 participants has demonstrated that is feasible to acquire prospective standardized research

Spinal Cord Injury Disrupts Resting-State Networks in the Human Brain.

PubMed

Hawasli, Ammar H; Rutlin, Jerrel; Roland, Jarod L; Murphy, Rory K J; Song, Sheng-Kwei; Leuthardt, Eric C; Shimony, Joshua S; Ray, Wilson Z

2018-03-15

Despite 253,000 spinal cord injury (SCI) patients in the United States, little is known about how SCI affects brain networks. Spinal MRI provides only structural information with no insight into functional connectivity. Resting-state functional MRI (RS-fMRI) quantifies network connectivity through the identification of resting-state networks (RSNs) and allows detection of functionally relevant changes during disease. Given the robust network of spinal cord afferents to the brain, we hypothesized that SCI produces meaningful changes in brain RSNs. RS-fMRIs and functional assessments were performed on 10 SCI subjects. Blood oxygen-dependent RS-fMRI sequences were acquired. Seed-based correlation mapping was performed using five RSNs: default-mode (DMN), dorsal-attention (DAN), salience (SAL), control (CON), and somatomotor (SMN). RSNs were compared with normal control subjects using false-discovery rate-corrected two way t tests. SCI reduced brain network connectivity within the SAL, SMN, and DMN and disrupted anti-correlated connectivity between CON and SMN. When divided into separate cohorts, complete but not incomplete SCI disrupted connectivity within SAL, DAN, SMN and DMN and between CON and SMN. Finally, connectivity changed over time after SCI: the primary motor cortex decreased connectivity with the primary somatosensory cortex, the visual cortex decreased connectivity with the primary motor cortex, and the visual cortex decreased connectivity with the sensory parietal cortex. These unique findings demonstrate the functional network plasticity that occurs in the brain as a result of injury to the spinal cord. Connectivity changes after SCI may serve as biomarkers to predict functional recovery following an SCI and guide future therapy.

Transplantation of Embryonic Spinal Cord Derived Cells Helps to Prevent Muscle Atrophy after Peripheral Nerve Injury

PubMed Central

Ruven, Carolin; Li, Wen; Li, Heng; Wong, Wai-Man; Wu, Wutian

2017-01-01

Injuries to peripheral nerves are frequent in serious traumas and spinal cord injuries. In addition to surgical approaches, other interventions, such as cell transplantation, should be considered to keep the muscles in good condition until the axons regenerate. In this study, E14.5 rat embryonic spinal cord fetal cells and cultured neural progenitor cells from different spinal cord segments were injected into transected musculocutaneous nerve of 200–300 g female Sprague Dawley (SD) rats, and atrophy in biceps brachii was assessed. Both kinds of cells were able to survive, extend their axons towards the muscle and form neuromuscular junctions that were functional in electromyographic studies. As a result, muscle endplates were preserved and atrophy was reduced. Furthermore, we observed that the fetal cells had a better effect in reducing the muscle atrophy compared to the pure neural progenitor cells, whereas lumbar cells were more beneficial compared to thoracic and cervical cells. In addition, fetal lumbar cells were used to supplement six weeks delayed surgical repair after the nerve transection. Cell transplantation helped to preserve the muscle endplates, which in turn lead to earlier functional recovery seen in behavioral test and electromyography. In conclusion, we were able to show that embryonic spinal cord derived cells, especially the lumbar fetal cells, are beneficial in the treatment of peripheral nerve injuries due to their ability to prevent the muscle atrophy. PMID:28264437

Successful Reinnervation of the Diaphragm After Intercostal to Phrenic Nerve Neurotization in Patients With High Spinal Cord Injury.

PubMed

Nandra, Kulvir S; Harari, Martin; Price, Thea P; Greaney, Patrick J; Weinstein, Michael S

2017-08-01

Our objective in this study was to extend diaphragmatic pacing therapy to include paraplegic patients with high cervical spinal cord injuries between C3 and C5. Diaphragmatic pacing has been used in patients experiencing ventilator-dependent respiratory failure due to spinal cord injury as a means to reduce or eliminate the need for mechanical ventilation. However, this technique relies on intact phrenic nerve function. Recently, phrenic nerve reconstruction with intercostal nerve grafting has expanded the indications for diaphragmatic pacing. Our study aimed to evaluate early outcomes and efficacy of intercostal nerve transfer in diaphragmatic pacing. Four ventilator-dependent patients with high cervical spinal cord injuries were selected for this study. Each patient demonstrated absence of phrenic nerve function via external neck stimulation and laparoscopic diaphragm mapping. Each patient underwent intercostal to phrenic nerve grafting with implantation of a phrenic nerve pacer. The patients were followed, and ventilator dependence was reassessed at 1 year postoperatively. Our primary outcome was measured by the amount of time our patients tolerated off the ventilator per day. We found that all 4 patients have tolerated paced breathing independent of mechanical ventilation, with 1 patient achieving 24 hours of tracheostomy collar. From this study, intercostal to phrenic nerve transfer seems to be a promising approach in reducing or eliminating ventilator support in patients with C3 to C5 high spinal cord injury.

Protective effect of nicotinamide adenine dinucleotide (NAD+) against spinal cord ischemia-reperfusion injury via reducing oxidative stress-induced neuronal apoptosis.

PubMed

Xie, Lei; Wang, Zhenfei; Li, Changwei; Yang, Kai; Liang, Yu

2017-02-01

As previous studies demonstrate that oxidative stress and apoptosis play crucial roles in ischemic pathogenesis and nicotinamide adenine dinucleotide (NAD + ) treatment attenuates oxidative stress-induced cell death among primary neurons and astrocytes as well as significantly reduce cerebral ischemic injury in rats. We used a spinal cord ischemia injury (SCII) model in rats to verify our hypothesis that NAD + could ameliorate oxidative stress-induced neuronal apoptosis. Adult male rats were subjected to transient spinal cord ischemia for 60min, and different doses of NAD + were administered intraperitoneally immediately after the start of reperfusion. Neurological function was determined by Basso, Beattie, Bresnahan (BBB) scores. The oxidative stress level was assessed by superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. The degree of apoptosis was analyzed by deoxyuridinetriphosphate nick-end labeling (TUNEL) staining and protein levels of cleaved caspase-3 and AIF (apoptosis inducing factor). The results showed that NAD + at 50 or 100mg/kg significantly decreased the oxidative stress level and neuronal apoptosis in the spinal cord of ischemia-reperfusion rats compared with saline, as accompanied with the decreased oxidative stress, NAD + administration significantly restrained the neuronal apoptosis after ischemia injury while improved the neurological and motor function. These findings suggested that NAD + might protect against spinal cord ischemia-reperfusion via reducing oxidative stress-induced neuronal apoptosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recent advancements in the SQUID magnetospinogram system

NASA Astrophysics Data System (ADS)

Adachi, Yoshiaki; Kawai, Jun; Haruta, Yasuhiro; Miyamoto, Masakazu; Kawabata, Shigenori; Sekihara, Kensuke; Uehara, Gen

2017-06-01

In this study, a new superconducting quantum interference device (SQUID) biomagnetic measurement system known as magnetospinogram (MSG) is developed. The MSG system is used for observation of a weak magnetic field distribution induced by the neural activity of the spinal cord over the body surface. The current source reconstruction for the observed magnetic field distribution provides noninvasive functional imaging of the spinal cord, which enables medical personnel to diagnose spinal cord diseases more accurately. The MSG system is equipped with a uniquely shaped cryostat and a sensor array of vector-type SQUID gradiometers that are designed to detect the magnetic field from deep sources across a narrow observation area over the body surface of supine subjects. The latest prototype of the MSG system is already applied in clinical studies to develop a diagnosis protocol for spinal cord diseases. Advancements in hardware and software for MSG signal processing and cryogenic components aid in effectively suppressing external magnetic field noise and reducing the cost of liquid helium that act as barriers with respect to the introduction of the MSG system to hospitals. The application of the MSG system is extended to various biomagnetic applications in addition to spinal cord functional imaging given the advantages of the MSG system for investigating deep sources. The study also includes a report on the recent advancements of the SQUID MSG system including its peripheral technologies and wide-spread applications.

Hydrogel-based scaffolds to support intrathecal stem cell transplantation as a gateway to the spinal cord: clinical needs, biomaterials, and imaging technologies.

PubMed

Oliveira, J Miguel; Carvalho, Luisa; Silva-Correia, Joana; Vieira, Sílvia; Majchrzak, Malgorzata; Lukomska, Barbara; Stanaszek, Luiza; Strymecka, Paulina; Malysz-Cymborska, Izabela; Golubczyk, Dominika; Kalkowski, Lukasz; Reis, Rui L; Janowski, Miroslaw; Walczak, Piotr

2018-01-01

The prospects for cell replacement in spinal cord diseases are impeded by inefficient stem cell delivery. The deep location of the spinal cord and complex surgical access, as well as densely packed vital structures, question the feasibility of the widespread use of multiple spinal cord punctures to inject stem cells. Disorders characterized by disseminated pathology are particularly appealing for the distribution of cells globally throughout the spinal cord in a minimally invasive fashion. The intrathecal space, with access to a relatively large surface area along the spinal cord, is an attractive route for global stem cell delivery, and, indeed, is highly promising, but the success of this approach relies on the ability of cells (1) to survive in the cerebrospinal fluid (CSF), (2) to adhere to the spinal cord surface, and (3) to migrate, ultimately, into the parenchyma. Intrathecal infusion of cell suspension, however, has been insufficient and we postulate that embedding transplanted cells within hydrogel scaffolds will facilitate reaching these goals. In this review, we focus on practical considerations that render the intrathecal approach clinically viable, and then discuss the characteristics of various biomaterials that are suitable to serve as scaffolds. We also propose strategies to modulate the local microenvironment with nanoparticle carriers to improve the functionality of cellular grafts. Finally, we provide an overview of imaging modalities for in vivo monitoring and characterization of biomaterials and stem cells. This comprehensive review should serve as a guide for those planning preclinical and clinical studies on intrathecal stem cell transplantation.

Why New Spinal Cord Plasticity Does Not Disrupt Old Motor Behaviors.

PubMed

Chen, Yi; Chen, Lu; Wang, Yu; Chen, Xiang Yang; Wolpaw, Jonathan R

2017-08-23

When new motor learning changes the spinal cord, old behaviors are not impaired; their key features are preserved by additional compensatory plasticity. To explore the mechanisms responsible for this compensatory plasticity, we transected the spinal dorsal ascending tract before or after female rats acquired a new behavior-operantly conditioned increase or decrease in the right soleus H-reflex-and examined an old behavior-locomotion. Neither spinal dorsal ascending tract transection nor H-reflex conditioning alone impaired locomotion. Nevertheless, when spinal dorsal ascending tract transection and H-reflex conditioning were combined, the rats developed a limp and a tilted posture that correlated in direction and magnitude with the H-reflex change. When the right H-reflex was increased by conditioning, the right step lasted longer than the left and the right hip was higher than the left; when the right H-reflex was decreased by conditioning, the opposite occurred. These results indicate that ascending sensory input guides the compensatory plasticity that normally prevents the plasticity underlying H-reflex change from impairing locomotion. They support the concept of the state of the spinal cord as a negotiated equilibrium that reflects the concurrent influences of all the behaviors in an individual's repertoire; and they support the new therapeutic strategies this concept introduces. SIGNIFICANCE STATEMENT The spinal cord provides a reliable final common pathway for motor behaviors throughout life. Until recently, its reliability was explained by the assumption that it is hardwired; but it is now clear that the spinal cord changes continually as new behaviors are acquired. Nevertheless, old behaviors are preserved. This study shows that their preservation depends on sensory feedback from the spinal cord to the brain: if feedback is removed, the acquisition of a new behavior may disrupt an old behavior. In sum, when a new behavior changes the spinal cord, sensory feedback to the brain guides further change that preserves old behaviors. This finding contributes to a new understanding of spinal cord function and to development of new rehabilitation therapies. Copyright © 2017 the authors 0270-6474/17/378198-09$15.00/0.

Preventive Effect of Intrathecal Paracetamol on Spinal Cord Injury in Rats

PubMed Central

Sahin, Murat; Sayar, Ilyas; Peker, Kemal; Gullu, Huriye; Yildiz, Huseyin

2014-01-01

Background: Ischemic injury of the spinal cord during the surgical repair of thoracoabdominal aortic aneurysms might lead to paraplegia. Although a number of different mechanisms have been proposed, the exact cause of paraplegia has remained unknown, hampering the development of effective pharmacologic or other strategies for prevention of this condition. A number of studies suggested that cyclooxygenases (COX) contribute to neural breakdown; thus, COX inhibitors might reduce injury. Objectives: We aimed to assess the preventive effect of intrathecal (IT) pretreatment with paracetamol on spinal cord injury in a rat model. Materials and Methods: This experimental study was performed in Ataturk University Animal Research Laboratory Center, Erzurum, Turkey. Adult male Wistar rats were randomly allocated to three experimental groups (n = 6) to receive IT physiologic saline (controls), 50 µg of paracetamol, or 100 µg paracetamol one hour before induction of spinal cord ischemia. Six other rats were considered as the sham group. For the assessment of ischemic injury, motor functions of the hind limbs and histopathologic changes of the lumbar spinal cord were evaluated. Additional 20 rats were divided into two equal groups for the second part of the study where the survival rates were recorded in controls and in animals receiving 100 µg of paracetamol during the 28-day observation period. Results: Pretreatment with 100 µg of paracetamol resulted in a significant improvement in motor functions and histopathologic findings (P < 0.05). Despite a higher rate of survival in 100 µg of paracetamol group (70%) at day 28, the difference was not statistically significant in comparison with controls. Conclusions: Our results suggest a protective effect of pretreatment with IT paracetamol on ischemic spinal cord injury during thoracolumbar aortic aneurysm surgery. PMID:25763224

A validity study of the Spanish-World Health Organization Quality of Life short version instrument in persons with traumatic spinal cord injury.

PubMed

Salvador-De La Barrera, Sebastián; Mora-Boga, Rubén; Ferreiro-Velasco, Mª Elena; Seoane-Pillado, Teresa; Montoto-Marqués, Antonio; Rodríguez-Sotillo, Antonio; Pertega Díaz, Sonia

2018-05-23

This was a psychometric study. To determine the validity of the Spanish version of the World Health Organization Quality of Life instrument (WHOQOL-BREF) for its use in persons with traumatic spinal cord injury and, as secondary objectives, to correlate the results with variables such as functional status, psychological well-being, and social support. Spinal Cord Injury Unit, Complejo Hospitalario Universitario de A Coruña, Galicia (Spain). Fifty-four people with spinal cord injury were enrolled in this study. Relevant variables were analyzed based on the scores reported by each participant in the Spanish versions of the WHOQOL-BREF questionnaire, the Spinal Cord Independence Measure, the Hospital Anxiety and Depression Scale (HADS), and the Duke-UNC Functional and Social Support Questionnaire. Both parametric and non-parametric tests were used to compare various variables. The instrument's internal consistency and test-retest reliability were also confirmed. The mean scores of each domain of the WHOQOL-BREF were lower, but nonsignificant, among people who need help to perform activities of daily living. The correlation between the scores obtained in the "Psychological" domain and the items of the HADS scale was significant. Significant differences were also observed when comparing the results of the "Social relationships" and "Environment" domains among people with low scores in the Duke questionnaire. Both an adequate consistency (Cronbach's α: 0.887) and test-retest reliability were demonstrated. The Spanish version of the WHOQOL-BREF questionnaire is useful and reliable to evaluate the quality of life of persons with spinal cord injuries in our population of Spanish-speaking people.

Men's adjustment to spinal cord injury: the unique contributions of conformity to masculine gender norms.

PubMed

Burns, Shaun Michael; Hough, Sigmund; Boyd, Briana L; Hill, Justin

2010-06-01

Men constitute 82% of the approximately 250,000 people in the United States living with a spinal cord injury. Unfortunately, however, little is known about the impact of men's adherence to gender norms on their adjustment to such injuries. The present investigation examined the utility of masculine norms in explaining variance in depression beyond that accounted for by commonly identified predictors of men's adjustment following spinal cord injury. As hypothesized, results suggested that men's adherence to masculine norms accounted for unique variance in their depression scores beyond that contributed by social support, environmental barriers/access, and erectile functioning. Respondents who adhered to norms stressing the primacy of men's work demonstrated lower rates of depression, whereas those who conformed to norms for self-reliance demonstrated higher depression scores. The authors discuss future research directions and potential psychotherapeutic strategies for working with men with spinal cord injuries.

Augmentation of Voluntary Locomotor Activity by Transcutaneous Spinal Cord Stimulation in Motor-Incomplete Spinal Cord-Injured Individuals.

PubMed

Hofstoetter, Ursula S; Krenn, Matthias; Danner, Simon M; Hofer, Christian; Kern, Helmut; McKay, William B; Mayr, Winfried; Minassian, Karen

2015-10-01

The level of sustainable excitability within lumbar spinal cord circuitries is one of the factors determining the functional outcome of locomotor therapy after motor-incomplete spinal cord injury. Here, we present initial data using noninvasive transcutaneous lumbar spinal cord stimulation (tSCS) to modulate this central state of excitability during voluntary treadmill stepping in three motor-incomplete spinal cord-injured individuals. Stimulation was applied at 30 Hz with an intensity that generated tingling sensations in the lower limb dermatomes, yet without producing muscle reflex activity. This stimulation changed muscle activation, gait kinematics, and the amount of manual assistance required from the therapists to maintain stepping with some interindividual differences. The effect on motor outputs during treadmill-stepping was essentially augmentative and step-phase dependent despite the invariant tonic stimulation. The most consistent modification was found in the gait kinematics, with the hip flexion during swing increased by 11.3° ± 5.6° across all subjects. This preliminary work suggests that tSCS provides for a background increase in activation of the lumbar spinal locomotor circuitry that has partially lost its descending drive. Voluntary inputs and step-related feedback build upon the stimulation-induced increased state of excitability in the generation of locomotor activity. Thus, tSCS essentially works as an electrical neuroprosthesis augmenting remaining motor control. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

The angiopoietin1-Akt pathway regulates barrier function of the cultured spinal cord microvascular endothelial cells through Eps8.

PubMed

Liu, Xinchun; Zhou, Xiaoshu; Yuan, Wei

2014-10-15

In mammalian central nervous system (CNS), the integrity of the blood-spinal cord barrier (BSCB), formed by tight junctions (TJs) between adjacent microvascular endothelial cells near the basement membrane of capillaries and the accessory structures, is important for relatively independent activities of the cellular constituents inside the spinal cord. The barrier function of the BSCB are tightly regulated and coordinated by a variety of physiological or pathological factors, similar with but not quite the same as its counterpart, the blood-brain barrier (BBB). Herein, angiopoietin 1 (Ang1), an identified ligand of the endothelium-specific tyrosine kinase receptor Tie-2, was verified to regulate barrier functions, including permeability, junction protein interactions and F-actin organization, in cultured spinal cord microvascular endothelial cells (SCMEC) of rat through the activity of Akt. Besides, these roles of Ang1 in the BSCB in vitro were found to be accompanied with an increasing expression of epidermal growth factor receptor pathway substrate 8 (Eps8), an F-actin bundling protein. Furthermore, the silencing of Eps8 by lentiviral shRNA resulted in an antagonistic effect vs. Ang1 on the endothelial barrier function of SCMEC. In summary, the Ang1-Akt pathway serves as a regulator in the barrier function modulation of SCMEC via the actin-binding protein Eps8. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

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.

Return to work following spinal cord injury: a review.

PubMed

Lidal, Ingeborg Beate; Huynh, Tuan Khai; Biering-Sørensen, Fin

2007-09-15

To review literature on return to work (RTW) and employment in persons with spinal cord injury (SCI), and present employment rates, factors influencing employment, and interventions aimed at helping people with SCI to obtain and sustain productive work. A systematic review for 2000 - 2006 was carried out in PubMed/Medline, AMED, (ISI) Web of Science, EMBASE, CINAHL, PsycInfo and Sociological abstracts database. The keywords 'spinal cord injuries', 'spinal cord disorder', 'spinal cord lesion' or 'spinal cord disease' were cross-indexed with 'employment', 'return to work', 'occupation' or 'vocational'. Out of approximately 270 hits, 110 references were used, plus 13 more found elsewhere. Among individuals with SCI working at the time of injury 21 - 67% returned to work after injury. RTW was higher in persons injured at a younger age, had less severe injuries and higher functional independence. Employment rate improved with time after SCI. Persons with SCI employed ranged from 11.5% to 74%. Individuals who sustained SCI during childhood or adolescence had higher adult employment rates. Most common reported barriers to employment were problems with transportation, health and physical limitations, lack of work experience, education or training, physical or architectural barriers, discrimination by employers, and loss of benefits. Individuals with SCI discontinue working at younger age. This review confirmed low employment rates after SCI. Future research should explore interventions aimed at helping people with SCI to obtain and sustain productive work.

Effect of thalidomide on signal transduction pathways and secondary damage in experimental spinal cord trauma.

PubMed

Genovese, Tiziana; Mazzon, Emanuela; Esposito, Emanuela; Di Paola, Rosanna; Caminiti, Rocco; Meli, Rosaria; Bramanti, Placido; Cuzzocrea, Salvatore

2008-09-01

TNF-alpha seems to play a central role in the inflammatory process of spinal cord injury. We tested the neuroprotective effects of thalidomide, an immunomodulatory agent that inhibits TNF-alpha production, which have not been investigated so far. The aim of our study was to evaluate the therapeutic efficacy of thalidomide in an experimental model of spinal cord trauma, which was induced by the application of vascular clips (force of 24 g) to the dura via a 4-level T5 to T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration, and cytokine production that is followed by recruitment of other inflammatory cells, production of a range of inflammation mediators, tissue damage, apoptosis, and disease. Thalidomide treatment significantly reduced the degree of: 1) spinal cord inflammation and tissue injury (histological score); 2) neutrophil infiltration (myeloperoxidase evaluation); 3) iNOS, nitrotyrosine, lipid peroxidation, and cytokine expression (TNF-alpha and IL-1beta); 4) apoptosis (terminal deoxynucleotidyltransferase-mediated UTP end labeling staining, and Bax and Bcl-2 expression); and 5) nuclear factor-kappaB activation. In a separate set of experiments, we have also clearly demonstrated that thalidomide significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with thalidomide reduces the development of inflammation and tissue injury events associated with spinal cord trauma.

Testosterone Plus Finasteride Treatment After Spinal Cord Injury

ClinicalTrials.gov

2018-05-16

Spinal Cord Injury; Spinal Cord Injuries; Trauma, Nervous System; Wounds and Injuries; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Gonadal Disorders; Endocrine System Diseases; Hypogonadism; Genital Diseases, Male

Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers

PubMed Central

Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I.; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew

2015-01-01

Abstract With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines—monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)—to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996

Genetically identified spinal interneurons integrating tactile afferents for motor control

PubMed Central

Panek, Izabela; Farah, Carl

2015-01-01

Our movements are shaped by our perception of the world as communicated by our senses. Perception of sensory information has been largely attributed to cortical activity. However, a prior level of sensory processing occurs in the spinal cord. Indeed, sensory inputs directly project to many spinal circuits, some of which communicate with motor circuits within the spinal cord. Therefore, the processing of sensory information for the purpose of ensuring proper movements is distributed between spinal and supraspinal circuits. The mechanisms underlying the integration of sensory information for motor control at the level of the spinal cord have yet to be fully described. Recent research has led to the characterization of spinal neuron populations that share common molecular identities. Identification of molecular markers that define specific populations of spinal neurons is a prerequisite to the application of genetic techniques devised to both delineate the function of these spinal neurons and their connectivity. This strategy has been used in the study of spinal neurons that receive tactile inputs from sensory neurons innervating the skin. As a result, the circuits that include these spinal neurons have been revealed to play important roles in specific aspects of motor function. We describe these genetically identified spinal neurons that integrate tactile information and the contribution of these studies to our understanding of how tactile information shapes motor output. Furthermore, we describe future opportunities that these circuits present for shedding light on the neural mechanisms of tactile processing. PMID:26445867

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

Spinal Plasticity and Behavior: BDNF-Induced Neuromodulation in Uninjured and Injured Spinal Cord

PubMed Central

Huie, J. Russell

2016-01-01

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophic factor family of signaling molecules. Since its discovery over three decades ago, BDNF has been identified as an important regulator of neuronal development, synaptic transmission, and cellular and synaptic plasticity and has been shown to function in the formation and maintenance of certain forms of memory. Neural plasticity that underlies learning and memory in the hippocampus shares distinct characteristics with spinal cord nociceptive plasticity. Research examining the role BDNF plays in spinal nociception and pain overwhelmingly suggests that BDNF promotes pronociceptive effects. BDNF induces synaptic facilitation and engages central sensitization-like mechanisms. Also, peripheral injury-induced neuropathic pain is often accompanied with increased spinal expression of BDNF. Research has extended to examine how spinal cord injury (SCI) influences BDNF plasticity and the effects BDNF has on sensory and motor functions after SCI. Functional recovery and adaptive plasticity after SCI are typically associated with upregulation of BDNF. Although neuropathic pain is a common consequence of SCI, the relation between BDNF and pain after SCI remains elusive. This article reviews recent literature and discusses the diverse actions of BDNF. We also highlight similarities and differences in BDNF-induced nociceptive plasticity in naïve and SCI conditions. PMID:27721996

Evaluation of normal appearing spinal cord by diffusion tensor imaging, fiber tracking, fractional anisotropy, and apparent diffusion coefficient measurement in 13 dogs

PubMed Central

2013-01-01

Background Functional magnetic resonance (fMR) imaging offers plenty of new opportunities in the diagnosis of central nervous system diseases. Diffusion tensor imaging (DTI) is a technique sensitive to the random motion of water providing information about tissue architecture. We applied DTI to normal appearing spinal cords of 13 dogs of different breeds and body weights in a 3.0 T magnetic resonance (MR) scanner. The aim was to study fiber tracking (FT) patterns by tractography and the variations of the fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) observed in the spinal cords of dogs with different sizes and at different locations (cervical and thoracolumbar). For that reason we added a DTI sequence to the standard clinical MR protocol. The values of FA and ADC were calculated by means of three regions of interest defined on the cervical or the thoracolumbar spinal cord (ROI 1, 2, and 3). Results The shape of the spinal cord fiber tracts was well illustrated following tractography and the exiting nerve roots could be differentiated from the spinal cord fiber tracts. Routine MR scanning times were extended for 8 to 12 min, depending on the size of the field of view (FOV), the slice thickness, and the size of the interslice gaps. In small breed dogs (< 15 kg body weight) the fibers could be tracked over a length of approximately 10 vertebral bodies with scanning times of about 8 min, whereas in large breed dogs (> 25 kg body weight) the traceable fiber length was about 5 vertebral bodies which took 10 to 12 min scanning time. FA and ADC values showed mean values of 0.447 (FA), and 0.560 × 10-3 mm2/s (ADC), respectively without any differences detected with regard to different dog sizes and spinal cord 45 segments examined. Conclusion FT is suitable for the graphical depiction of the canine spinal cord and the exiting nerve roots. The FA and ADC values offer an objective measure for evaluation of the spinal cord fiber integrity in dogs. PMID:23618404

Emergence of Serotonergic Neurons After Spinal Cord Injury in Turtles

PubMed Central

Fabbiani, Gabriela; Rehermann, María I.; Aldecosea, Carina; Trujillo-Cenóz, Omar; Russo, Raúl E.

2018-01-01

Plasticity of neural circuits takes many forms and plays a fundamental role in regulating behavior to changing demands while maintaining stability. For example, during spinal cord development neurotransmitter identity in neurons is dynamically adjusted in response to changes in the activity of spinal networks. It is reasonable to speculate that this type of plasticity might occur also in mature spinal circuits in response to injury. Because serotonergic signaling has a central role in spinal cord functions, we hypothesized that spinal cord injury (SCI) in the fresh water turtle Trachemys scripta elegans may trigger homeostatic changes in serotonergic innervation. To test this possibility we performed immunohistochemistry for serotonin (5-HT) and key molecules involved in the determination of the serotonergic phenotype before and after SCI. We found that as expected, in the acute phase after injury the dense serotonergic innervation was strongly reduced. However, 30 days after SCI the population of serotonergic cells (5-HT+) increased in segments caudal to the lesion site. These cells expressed the neuronal marker HuC/D and the transcription factor Nkx6.1. The new serotonergic neurons did not incorporate the thymidine analog 5-bromo-2′-deoxyuridine (BrdU) and did not express the proliferating cell nuclear antigen (PCNA) indicating that novel serotonergic neurons were not newborn but post-mitotic cells that have changed their neurochemical identity. Switching towards a serotonergic neurotransmitter phenotype may be a spinal cord homeostatic mechanism to compensate for the loss of descending serotonergic neuromodulation, thereby helping the outstanding functional recovery displayed by turtles. The 5-HT1A receptor agonist (±)-8-Hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT) blocked the increase in 5-HT+ cells suggesting 5-HT1A receptors may trigger the respecification process. PMID:29593503

North American Clinical Trials Network (NACTN) for Treatment of Spinal Cord Injury: A Consortium of Military, Veterans Administration, and Civilian Hospitals

DTIC Science & Technology

2011-01-31

of the patient on arrival and includes a clinical evaluation, 5 measurement of state of consciousness with the Glasgow Coma Scale (GCS) and of...associated injuries with the Abbreviated Injury Scale . The American Spinal Injury Association impairment scale (AIS) is scored on admission and at key...the AIS Impairment Scale , and where appropriate, the Functional Independence Measure FIM™, the Spinal Cord Independence Measure (SCIM), and the

Transspinal direct current stimulation modulates migration and proliferation of adult newly born spinal cells in mice.

PubMed

Samaddar, Sreyashi; Vazquez, Kizzy; Ponkia, Dipen; Toruno, Pedro; Sahbani, Karim; Begum, Sultana; Abouelela, Ahmed; Mekhael, Wagdy; Ahmed, Zaghloul

2017-02-01

Direct current electrical fields have been shown to be a major factor in the regulation of cell proliferation, differentiation, migration, and survival, as well as in the maturation of dividing cells during development. During adulthood, spinal cord cells are continuously produced in both animals and humans, and they hold great potential for neural restoration following spinal cord injury. While the effects of direct current electrical fields on adult-born spinal cells cultured ex vivo have recently been reported, the effects of direct current electrical fields on adult-born spinal cells in vivo have not been characterized. Here, we provide convincing findings that a therapeutic form of transspinal direct current stimulation (tsDCS) affects the migration and proliferation of adult-born spinal cells in mice. Specifically, cathodal tsDCS attracted the adult-born spinal cells, while anodal tsDCS repulsed them. In addition, both tsDCS polarities caused a significant increase in cell number. Regarding the potential mechanisms involved, both cathodal and anodal tsDCS caused significant increases in expression of brain-derived neurotrophic factor, while expression of nerve growth factor increased and decreased, respectively. In the spinal cord, both anodal and cathodal tsDCS increased blood flow. Since blood flow and angiogenesis are associated with the proliferation of neural stem cells, increased blood flow may represent a major factor in the modulation of newly born spinal cells by tsDCS. Consequently, we propose that the method and novel findings presented in the current study have the potential to facilitate cellular, molecular, and/or bioengineering strategies to repair injured spinal cords. NEW & NOTEWORTHY Our results indicate that transspinal direct current stimulation (tsDCS) affects the migratory pattern and proliferation of adult newly born spinal cells, a cell population which has been implicated in learning and memory. In addition, our results suggest a potential mechanism of action regarding the functional effects of applying direct current. Thus tsDCS may represent a novel method by which to manipulate the migration and cell number of adult newly born cells and restore functions following brain or spinal cord injury. Copyright © 2017 the American Physiological Society.

Managing the stigma: Exploring body image experiences and self-presentation among people with spinal cord injury.

PubMed

Bailey, K Alysse; Gammage, Kimberley L; van Ingen, Cathy; Ditor, David S

2016-01-01

Using modified constructivist grounded theory, the purpose of this study was to explore body image experiences in people with spinal cord injury. Nine participants (five women, four men) varying in age (21-63 years), type of injury (C3-T7; complete and incomplete), and years post-injury (4-36 years) took part in semi-structured in-depth interviews. The following main categories were found: appearance, weight concerns, negative functional features, impact of others, body disconnection, hygiene and incontinence, and self-presentation. Findings have implications for the health and well-being of those living with a spinal cord injury.

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.

A potential protective effect of α-tocopherol on vascular complication in spinal cord reperfusion injury in rats

PubMed Central

2010-01-01

Background Paraplegia remains a potential complication of spinal cord ischemic reperfusion injury (IRI) in which oxidative stress induced cyclooxygenase activities may contribute to ischemic neuronal damage. Prolonged administration of vitamin E (α-TOL), as a potent biological antioxidant, may have a protective role in this oxidative inflammatory ischemic cascade to reduce the incidence of paraplegia. The present study was designed to evaluate the preventive value of α-TOL in IRI of spinal cord. Methods For this study, 50 male Sprague-Dawley rats were used and divided into five experimental groups (n = 10): Control group (C); α-TOL control group (CE) which received intramuscular (i.m.) α-TOL injections (600 mg/kg); Sham operated group (S), IRI rats were subjected to laparotomy and clamping of the aorta just above the bifurcation for 45 min, then the clamp was released for 48 hrs for reperfusion; and IRIE rats group, received 600 mg/kg of α-TOL i.m. twice weekly for 6 weeks, followed by induction of IRI similar to the IRI group. At the end of the experimental protocol; motor, sensory and placing/stepping reflex evaluation was done. Plasma nitrite/nitrate (NOx) was measured. Then animals' spinal cord lumbar segments were harvested and homogenized for measurement of the levels of prostaglandin E2 (PGE2), malondialdehyde (MDA) and advanced oxidation products (AOPP), while superoxide dismutase (SOD) and catalase (CAT) activity were evaluated. Results Induction of IRI in rats resulted in significant increases in plasma levels of nitrite/nitrate (p < 0.001) and spinal cord homogenate levels of PGE2, MDA, advanced oxidation protein products AOPP and SOD with significant reduction (p < 0.001) in CAT homogenate levels. Significant impairment of motor, sensory functions and placing/stepping reflex was observed with IRI induction in the spinal cord (p < 0.001). α-TOL administration in IRIE group significantly improved all the previously measured parameters compared with IRI group. Conclusions α-TOL administration significantly prevents the damage caused by spinal cord IRI in rats with subsequent recovery of both motor and sensory functions. Alpha-tocopherol improves the oxidative stress level with subsequent reduction of the incidence of neurological deficits due to spinal cord IRI conditions. PMID:20609232

Drug overdose resulting in quadriplegia.

PubMed

Wang, Teresa S; Grunch, Betsy H; Moreno, Jessica R; Bagley, Carlos A; Gottfried, Oren N

2012-06-01

To describe a case of cervical flexion myelopathy resulting from a drug overdose. A 56-year-old male presented to the emergency department unable to move his extremities following drug overdose. Neurological examination revealed him to be at C6 ASIA A spinal cord injury. The CT of his cervical spine revealed no fracture; however, an MRI revealed cord edema extending from C3 to C6 as well as posterior paraspinal signal abnormalities suggestive of ligamentous injury. The patient underwent a posterior cervical laminectomy and fusion from C3 to C7. Neurologically he regained 3/5 bilateral tricep function and 2/5 grip; otherwise, he remained at ASIA A spinal cord injury at 6 months. Our patient suffered a spinal cord injury likely due to existing cervical stenosis, and in addition to an overdose of sedating medications, he likely sat in flexed neck position for prolonged period of time with the inability to modify his position. This likely resulted in cervical spine vascular and/or neurological compromise producing an irreversible spinal cord injury. Spinal cord injury is a rare finding in patients presenting with drug overdose. The lack of physical exam findings suggestive of trauma may delay prompt diagnosis and treatment, and thus clinicians must have a high index of suspicion when evaluating patients in this setting.

Low-energy extracorporeal shock wave therapy for promotion of vascular endothelial growth factor expression and angiogenesis and improvement of locomotor and sensory functions after spinal cord injury.

PubMed

Yahata, Kenichiro; Kanno, Haruo; Ozawa, Hiroshi; Yamaya, Seiji; Tateda, Satoshi; Ito, Kenta; Shimokawa, Hiroaki; Itoi, Eiji

2016-12-01

OBJECTIVE Extracorporeal shock wave therapy (ESWT) is widely used to treat various human diseases. Low-energy ESWT increases expression of vascular endothelial growth factor (VEGF) in cultured endothelial cells. The VEGF stimulates not only endothelial cells to promote angiogenesis but also neural cells to induce neuroprotective effects. A previous study by these authors demonstrated that low-energy ESWT promoted expression of VEGF in damaged neural tissue and improved locomotor function after spinal cord injury (SCI). However, the neuroprotective mechanisms in the injured spinal cord produced by low-energy ESWT are still unknown. In the present study, the authors investigated the cell specificity of VEGF expression in injured spinal cords and angiogenesis induced by low-energy ESWT. They also examined the neuroprotective effects of low-energy ESWT on cell death, axonal damage, and white matter sparing as well as the therapeutic effect for improvement of sensory function following SCI. METHODS Adult female Sprague-Dawley rats were divided into the SCI group (SCI only) and SCI-SW group (low-energy ESWT applied after SCI). Thoracic SCI was produced using a New York University Impactor. Low-energy ESWT was applied to the injured spinal cord 3 times a week for 3 weeks after SCI. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan open-field locomotor score for 42 days after SCI. Mechanical and thermal allodynia in the hindpaw were evaluated for 42 days. Double staining for VEGF and various cell-type markers (NeuN, GFAP, and Olig2) was performed at Day 7; TUNEL staining was also performed at Day 7. Immunohistochemical staining for CD31, α-SMA, and 5-HT was performed on spinal cord sections taken 42 days after SCI. Luxol fast blue staining was performed at Day 42. RESULTS Low-energy ESWT significantly improved not only locomotion but also mechanical and thermal allodynia following SCI. In the double staining, expression of VEGF was observed in NeuN-, GFAP-, and Olig2-labeled cells. Low-energy ESWT significantly promoted CD31 and α-SMA expressions in the injured spinal cords. In addition, low-energy ESWT significantly reduced the TUNEL-positive cells in the injured spinal cords. Furthermore, the immunodensity of 5-HT-positive axons was significantly higher in the animals treated by low-energy ESWT. The areas of spared white matter were obviously larger in the SCI-SW group than in the SCI group, as indicated by Luxol fast blue staining. CONCLUSIONS The results of this study suggested that low-energy ESWT promotes VEGF expression in various neural cells and enhances angiogenesis in damaged neural tissue after SCI. Furthermore, the neuroprotective effect of VEGF induced by low-energy ESWT can suppress cell death and axonal damage and consequently improve locomotor and sensory functions after SCI. Thus, low-energy ESWT can be a novel therapeutic strategy for treatment of SCI.

CD8+ T Cells Cause Disability and Axon Loss in a Mouse Model of Multiple Sclerosis

PubMed Central

Schmalstieg, William F.; Sauer, Brian M.; Wang, Huan; German, Christopher L.; Windebank, Anthony J.; Rodriguez, Moses; Howe, Charles L.

2010-01-01

Background The objective of this study was to test the hypothesis that CD8+ T cells directly mediate motor disability and axon injury in the demyelinated central nervous system. We have previously observed that genetic deletion of the CD8+ T cell effector molecule perforin leads to preservation of motor function and preservation of spinal axons in chronically demyelinated mice. Methodology/Principal Findings To determine if CD8+ T cells are necessary and sufficient to directly injure demyelinated axons, we adoptively transferred purified perforin-competent CD8+ spinal cord-infiltrating T cells into profoundly demyelinated but functionally preserved perforin-deficient host mice. Transfer of CD8+ spinal cord-infiltrating T cells rapidly and irreversibly impaired motor function, disrupted spinal cord motor conduction, and reduced the number of medium- and large-caliber spinal axons. Likewise, immunodepletion of CD8+ T cells from chronically demyelinated wildtype mice preserved motor function and limited axon loss without altering other disease parameters. Conclusions/Significance In multiple sclerosis patients, CD8+ T cells outnumber CD4+ T cells in active lesions and the number of CD8+ T cells correlates with the extent of ongoing axon injury and functional disability. Our findings suggest that CD8+ T cells may directly injure demyelinated axons and are therefore a viable therapeutic target to protect axons and motor function in patients with multiple sclerosis. PMID:20814579

Fatty Acid Binding Protein 5 Modulates Docosahexaenoic Acid-Induced Recovery in Rats Undergoing Spinal Cord Injury

PubMed Central

Figueroa, Johnny D.; Serrano-Illan, Miguel; Licero, Jenniffer; Cordero, Kathia; Miranda, Jorge D.

2016-01-01

Abstract Omega-3 polyunsaturated fatty acids (n-3 PUFAs) promote functional recovery in rats undergoing spinal cord injury (SCI). However, the precise molecular mechanism coupling n-3 PUFAs to neurorestorative responses is not well understood. The aim of the present study was to determine the spatiotemporal expression of fatty acid binding protein 5 (FABP5) after contusive SCI and to investigate whether this protein plays a role in n-3 PUFA–mediated functional recovery post-SCI. We found that SCI resulted in a robust spinal cord up-regulation in FABP5 mRNA levels (556 ± 187%) and protein expression (518 ± 195%), when compared to sham-operated rats, at 7 days post-injury (dpi). This upregulation coincided with significant alterations in the metabolism of fatty acids in the injured spinal cord, as revealed by metabolomics-based lipid analyses. In particular, we found increased levels of the n-3 series PUFAs, particularly docosahexaenoic acid (DHA; 22:6 n-3) and eicosapentaenoic acid (EPA; 20:5 n-3) at 7 dpi. Animals consuming a diet rich in DHA and EPA exhibited a significant upregulation in FABP5 mRNA levels at 7 dpi. Immunofluorescence showed low basal FABP5 immunoreactivity in spinal cord ventral gray matter NeuN+ neurons of sham-operated rats. SCI resulted in a robust induction of FABP5 in glial (GFAP+, APC+, and NG2+) and precursor cells (DCX+, nestin+). We found that continuous intrathecal administration of FABP5 silencing with small interfering RNA (2 μg) impaired spontaneous open-field locomotion post-SCI. Further, FABP5 siRNA administration hindered the beneficial effects of DHA to ameliorate functional recovery at 7 dpi. Altogether, our findings suggest that FABP5 may be an important player in the promotion of cellular uptake, transport, and/or metabolism of DHA post-SCI. Given the beneficial roles of n-3 PUFAs in ameliorating functional recovery, we propose that FABP5 is an important contributor to basic repair mechanisms in the injured spinal cord. PMID:26715431

[Acute-stage para- and tetraplegia].

PubMed

Hachen, H J

1993-03-20

A quarter of a century ago, in October 1964, the first spinal cord injury center in Switzerland was opened at Geneva University Hospital. At that time all para- and tetraplegics were classified as "high-risk" patients. Early mortality, covering the initial four weeks following trauma, was still around 15%. The available resources for diagnostic assessment were limited to clinical examination and neuroradiological assessment (subsequently improved by the introduction of tomography and gas myelography). A great many patients suffered a deteriorated neurological level due to inadequate, multiple transfers between hospitals. Most patients who are paralyzed following a road-traffic accident show severe polytrauma. Their chances of survival and functional recovery have greatly improved in recent years due to efficient emergency transport by helicopter, admission to an intensive care unit (respiratory therapy, prophylactic anticoagulation, gastrointestinal cytoprotection, prevention of pressure sores, etc.) and a comprehensive medico-surgical team approach (orthopedic surgeons, neurosurgeons, ICU specialists, internists, etc.). Evaluation of the spine and spinal cord by NMR and CT scan allows precise assessment of the extent of CNS damage and provides additional guide-lines regarding efficient surgical reposition and spinal fusion. Ongoing experimental research in neurophysiology and neurobiochemistry of the brain and spinal cord is presently yielding some interesting results which hold out new hopes for functional recovery in some specific types of incomplete spinal cord trauma.

Effects of aquaporin 4 and inward rectifier potassium channel 4.1 on medullospinal edema after methylprednisolone treatment to suppress acute spinal cord injury in rats.

PubMed

Li, Ye; Hu, Haifeng; Liu, Jingchen; Zhu, Qingsan; Gu, Rui

2018-02-01

To investigate the effects of aquaporin 4 (AQP4) and inward rectifier potassium channel 4.1 (Kir4.1) on medullospinal edema after treatment with methylprednisolone (MP) to suppress acute spinal cord injury (ASCI) in rats. Sprague Dawley rats were randomly divided into control, sham, ASCI, and MP-treated ASCI groups. After the induction of ASCI, we injected 30 mg/kg MP via the tail vein at various time points. The Tarlov scoring method was applied to evaluate neurological symptoms, and the wet-dry weights method was applied to measure the water content of the spinal cord. The motor function score of the ASCI group was significantly lower than that of the sham group, and the spinal water content was significantly increased. In addition, the levels of AQP4 and Kir4.1 were significantly increased, as was their degree of coexpression. Compared with that in the ASCI group, the motor function score and the water content were significantly increased in the MP group; in addition, the expression and coexpression of AQP4 and Kir4.1 were significantly reduced. Methylprednisolone inhibited medullospinal edema in rats with acute spinal cord injury, possibly by reducing the coexpression of aquaporin 4 and Kir4.1 in medullospinal tissues.

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.

Autonomic cardiovascular control and sports classification in Paralympic athletes with spinal cord injury.

PubMed

West, Christopher R; Krassioukov, Andrei V

2017-01-01

Purpose To investigate the relationship between the classification systems used in wheelchair sports and cardiovascular function in Paralympic athletes with spinal cord injury (SCI). Methods 26 wheelchair rugby (C3-C8) and 14 wheelchair basketball (T3-L1) were assessed for their International Wheelchair Rugby and Basketball Federation sports classification. Next, athletes were assessed for resting and reflex cardiovascular and autonomic function via the change (delta) in systolic blood pressure (SBP) and heart rate (HR) in response to sit-up, and sympathetic skin responses (SSRs), respectively. Results There were no differences in supine, seated, or delta SBP and HR between different sport classes in rugby or basketball (all p > 0.23). Athletes with autonomically complete injuries (SSR score 0-1) exhibited a lower supine SBP, seated SBP and delta SBP compared to those with autonomically incomplete injuries (SSR score >1; all p < 0.010), independent of sport played. There was no association between self-report OH and measured OH (χ 2  =   1.63, p = 0.20). Conclusion We provide definitive evidence that sports specific classification is not related to the degree of remaining autonomic cardiovascular control in Paralympic athletes with SCI. We suggest that testing for remaining autonomic function, which is closely related to the degree of cardiovascular control, should be incorporated into sporting classification. Implications for Rehabilitation Spinal cord injury is a debilitating condition that affects the function of almost every physiological system. It is becoming increasingly apparent that spinal cord injury induced changes in autonomic and cardiovascular function are important determinants of sports performance in athletes with spinal cord injury. This study shows that the current sports classification systems used in wheelchair rugby and basketball do not accurately reflect autonomic and cardiovascular function and thus are placing some athletes at a distinct disadvantage/advantage within their respective sport.

Effects of cerebrolysin on motor-neuron-like NSC-34 cells

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

Keilhoff, Gerburg, E-mail: Gerburg.keilhoff@med.ovgu.de; Lucas, Benjamin; Pinkernelle, Josephine

Although the peripheral nervous system is capable of regeneration, this capability is limited. As a potential means of augmenting nerve regeneration, the effects of cerebrolysin (CL) – a proteolytic peptide fraction – were tested in vitro on the motor-neuron-like NSC-34 cell line and organotypic spinal cord cultures. Therefore, NSC-34 cells were subjected to mechanical stress by changing media and metabolic stress by oxygen glucose deprivation. Afterwards, cell survival/proliferation using MTT and BrdU-labeling (FACS) and neurite sprouting using ImageJ analysis were evaluated. Calpain-1, Src and α-spectrin protein expression were analyzed by Western blot. In organotypic cultures, the effect of CL onmore » motor neuron survival and neurite sprouting was tested by immunohistochemistry. CL had a temporary anti-proliferative but initially neuroprotective effect on OGD-stressed NSC-34 cells. High-dosed or repeatedly applied CL was deleterious for cell survival. CL amplified neurite reconstruction to limited extent, affected calpain-1 protein expression and influenced calpain-mediated spectrin cleavage as a function of Src expression. In organotypic spinal cord slice cultures, CL was not able to support motor neuron survival/neurite sprouting. Moreover, it hampered astroglia and microglia activities. The data suggest that CL may have only isolated positive effects on injured spinal motor neurons. High-dosed or accumulated CL seemed to have adverse effects in treatment of spinal cord injury. Further experiments are required to optimize the conditions for a safe clinical administration of CL in spinal cord injuries. - Highlights: • Cerebrolysin (CL) is anti-proliferative but initially neuroprotective in OGD-stressed NSC-34 cells. • CL amplified neurite reconstruction of NSC-34 cells. • CL affected calpain-1 expression and calpain-mediated spectrin cleavage as function of Src expression. • In organotypic spinal cord cultures, CL hampered motor neuron survival and glia activity. • Findings pose a contraindication for unchallenged use of CL in spinal cord injuries.« less

Effects of cathodal trans-spinal direct current stimulation on lower urinary tract function in normal and spinal cord injury mice with overactive bladder

NASA Astrophysics Data System (ADS)

Ahmed, Zaghloul

2017-10-01

Objective. Lower urinary tract (LUT) dysfunction is a monumental problem affecting quality of life following neurotrauma, such as spinal cord injury (SCI). Proper function of the bladder and its associated structures depends on coordinated activity of the neuronal circuitry in the spinal cord and brain. Disconnection between the spinal and brain centers controlling the LUT causes fundamental changes in the mechanisms involved in the micturition and storage reflexes. We investigated the effects of cathodal trans-spinal direct current stimulation (c-tsDCS) of the lumbosacral spine on bladder and external urinary sphincter (EUS) functions. Approach. We used cystometry and electromyography (EMG), in mice with and without SCI. Main results. c-tsDCS caused initiation of the micturition reflex in urethane-anesthetized normal mice with depressed micturition reflexes. This effect was associated with normalized EUS-EMG activity. Moreover, in urethane-anesthetized normal mice with expressed micturition reflexes, c-tsDCS increased the firing frequency, amplitude, and duration of EUS-EMG activity. These effects were associated with increased maximum intravesical pressure (P max) and intercontraction interval (ICI). In conscious normal animals, c-tsDCS caused significant increases in P max, ICI, threshold pressure (P thres), baseline pressure (P base), and number and amplitude of non-voiding contractions (NVCnumb and P im, respectively). In conscious mice with severe contusive SCI and overactive bladder, c-tsDCS increased P max, ICI, and P thres, but decreased P base, NVCnumb, and P im. c-tsDCS reduced the detrusor-overactivity/cystometry ratio, which is a measure of bladder overactivity associated with renal deterioration. Significance. These results indicate that c-tsDCS induces robust modulation of the lumbosacral spinal-cord circuitry that controls the LUT.

Overreaching in coordination dynamics therapy in an athlete with a spinal cord injury.

PubMed

Schalow, G; Vaher, I; Jaigma, P

2008-03-01

A motocross athlete suffered a clinically complete spinal cord injury (SCI) during competition. Although MRIs (magnetic resonance imaging) showed a complete spinal cord injury at the Thoracic 11/12 levels, surface EMG recordings indicated the survival of few tract fibres across the injury site. Six weeks after the accident the subject began intensive Coordination Dynamics Therapy (CDT) at an up-to-date therapy centre. The subject trained at his physical limits to induce structural and functional repair. Exercising at variable loads between 20 and 200N (on a special CDT and recording device) generated periods of overreaching and super-compensation. By plotting coordination dynamics values (kinesiology), including high-load exertion (200N) and hysteresis curves, periods of overreaching and super-compensation were made graphically visible. It was found that symmetrical improvements of central nervous system (CNS) functioning occurred during overreaching. Improvements in spinal cord functioning were achieved throughout one year of CDT in this chronically injured subject with an almost anatomically complete SCI. It is discussed that the measuring of CNS functions by means of recording coordination dynamics is a powerful and non-invasive tool ideal for exact quantitative and qualitative measurements of improvement (or change) in CNS functioning. Such diagnostics may be of particular importance in sport during training and before competition. Also, coordination dynamics might be used to measure the effects of prolonged exposure to reduced gravitational conditions on CNS functions, such as faced by astronauts.

Swiss national community survey on functioning after spinal cord injury: Protocol, characteristics of participants and determinants of non-response.

PubMed

Brinkhof, Martin W G; Fekete, Christine; Chamberlain, Jonviea D; Post, Marcel W M; Gemperli, Armin

2016-02-01

To detail the protocol, recruitment, study population, response, and data quality of the first population-based community survey of the Swiss Spinal Cord Injury (SwiSCI) Cohort Study. The survey consisted of 3 successive modules administered between September 2011 and March 2013. The first two modules queried demographics, lesion characteristics and key domains of functioning. The third module collected information on psychological personal factors and health behaviour; work integration; or health services and aging. Community-dwelling persons with chronic spinal cord injury in Switzerland. Descriptive analyses of the recruitment process, participant characteristics, and correspondence between self-reported and clinical data. Determinants for participation and the impact of non-response on survey results were assessed. Out of 3,144 eligible persons 1,549 participated in the first two modules (cumulative response rate 49.3%). Approximately three-quarters of participants were male, with a median age of 53 years, and 78% had traumatic spinal cord injury. Record-linkage with medical records demonstrated substantial agreement with self-reported demographic and lesion characteristics. A minimal non-response bias was found. The community survey was effective in recruiting an unbiased sample, thus providing valuable information to study functioning, health maintenance, and quality of life in the Swiss SCI community.

Magnetic Resonance Imaging of the Codman Microsensor Transducer Used for Intraspinal Pressure Monitoring: Findings From the Injured Spinal Cord Pressure Evaluation Study.

PubMed

Phang, Isaac; Mada, Marius; Kolias, Angelos G; Newcombe, Virginia F J; Trivedi, Rikin A; Carpenter, Adrian; Hawkes, Rob C; Papadopoulos, Marios C

2016-05-01

Laboratory and human study. To test the Codman Microsensor Transducer (CMT) in a cervical gel phantom. To test the CMT inserted to monitor intraspinal pressure in a patient with spinal cord injury. We recently introduced the technique of intraspinal pressure monitoring using the CMT to guide management of traumatic spinal cord injury [Werndle et al. Crit Care Med 2014;42:646]. This is analogous to intracranial pressure monitoring to guide management of patients with traumatic brain injury. It is unclear whether magnetic resonance imaging (MRI) of patients with spinal cord injury is safe with the intraspinal pressure CMT in situ. We measured the heating produced by the CMT placed in a gel phantom in various configurations. A 3-T MRI system was used with the body transmit coil and the spine array receive coil. A CMT was then inserted subdurally at the injury site in a patient who had traumatic spinal cord injury and MRI was performed at 1.5 T. In the gel phantom, heating of up to 5°C occurred with the transducer wire placed straight through the magnet bore. The heating was abolished when the CMT wire was coiled and passed away from the bore. We then tested the CMT in a patient with an American Spinal Injuries Association grade C cervical cord injury. The CMT wire was placed in the configuration that abolished heating in the gel phantom. Good-quality T1 and T2 images of the cord were obtained without neurological deterioration. The transducer remained functional after the MRI. Our data suggest that the CMT is MR conditional when used in the spinal configuration in humans. Data from a large patient group are required to confirm these findings. N/A.

Pathology of radiation injury to the canine spinal cord.

PubMed

Powers, B E; Beck, E R; Gillette, E L; Gould, D H; LeCouter, R A

1992-01-01

The histopathologic response of the canine spinal cord to fractionated doses of radiation was investigated. Forty-two dogs received 0, 44, 52, 60, or 68 Gy in 4 Gy fractions to the thoracic spinal cord. Dogs were evaluated for neurologic signs and were observed for 1 or 2 years after irradiation. Six major lesion types were observed; five in the irradiated spinal cord and one in irradiated dorsal root ganglia. The three most severe spinal cord lesions were white matter necrosis, massive hemorrhage, and segmental parenchymal atrophy which had an ED50 of 56.9 Gy (51.3-63.3 Gy 95% CI) in 4 Gy fractions. These lesions were consistently associated with abnormal neurologic signs. Radiation damage to the vasculature was the most likely cause of these three lesions. The two less severe spinal cord lesions were focal fiber loss, which had an ED50 of 49.5 Gy (44.8-53.6 Gy 95% CI) in 4 gy fractions and scattered white matter vacuolation that occurred at all doses. These less severe lesions were not consistently associated with neurologic signs and indicated the presence of residual damage that may occur after lower doses of radiation. Radiation damage to glial cells, axons, and/or vasculature were possible causes of these lesions. In the irradiated dorsal root ganglia, affected sensory neurons contained large intracytoplasmic vacuoles, and there was loss of neurons and satellite cells. Such alterations could affect sensory function. The dog is a good model for spinal cord irradiation studies as tolerance doses for lesions causing clinical signs are close to the estimated tolerance doses for humans, and studies involving volume and long-term observation can be done.

Oligodendrocyte precursor cell transplantation promotes functional recovery following contusive spinal cord injury in rats and is associated with altered microRNA expression

PubMed Central

Yang, Jin; Xiong, Liu-Lin; Wang, You-Cui; He, Xiang; Jiang, Ling; Fu, Song-Jun; Han, Xue-Fei; Liu, Jia; Wang, Ting-Hua

2018-01-01

It has been reported that oligodendrocyte precursor cells (OPCs) may be used to treat contusive spinal cord injury (SCC), and may alter microRNA (miRNA/miR) expression following SCC in rats. However, the association between miRNA expression and the treatment of rats with SCC with OPC transplantation remain unclear. The present study transplanted OPCs into the spinal cord of rats with SCC and subsequently used the Basso, Beattie and Bresnahan (BBB) score to assess the functional recovery and pain scores. An miRNA assay was performed to detect differentially expressed miRNAs in the spinal cord of SCC rats transplanted with OPCs, compared with SCC rats transplanted with medium. Quantitative polymerase chain reaction was used to verify significantly altered miRNA expression levels. The results demonstrated that OPC transplantation was able to improve motor recovery and relieve mechanical allodynia in rats with SCC. In addition, through a miRNA assay, 45 differentially expressed miRNAs (40 upregulated miRNAs and 5 downregulated miRNAs) were detected in the spinal cord of rats in the OPC group compared with in the Medium group. Differentially expressed miRNAs were identified according to the following criteria: Fold change >2 and P<0.05. Furthermore, quantitative polymerase chain reaction was used to verify the most highly upregulated (miR-375-3p and miR-1-3p) and downregulated (miR-363-3p, miR-449a-5p and miR-3074) spinal cord miRNAs that were identified in the miRNA assay. In addition, a bioinformatics analysis of these miRNAs indicated that miR-375 and miR-1 may act primarily to inhibit cell proliferation and apoptosis via transcriptional and translational regulation, whereas miR-363, miR-449a and miR-3074 may act primarily to inhibit cell proliferation and neuronal differentiation through transcriptional regulation. These results suggested that OPC transplantation may promote functional recovery of rats with SCC, which may be associated with the expression of various miRNAs in the spinal cord, including miR-375-3p, miR-1-3p, miR-363-3p, miR-449a-5p and miR-3074. PMID:29115639

Biomechanical properties of the spinal cord: implications for tissue engineering and clinical translation.

PubMed

Bartlett, Richard D; Choi, David; Phillips, James B

2016-10-01

Spinal cord injury is a severely debilitating condition which can leave individuals paralyzed and suffering from autonomic dysfunction. Regenerative medicine may offer a promising solution to this problem. Previous research has focused primarily on exploring the cellular and biological aspects of the spinal cord, yet relatively little remains known about the biomechanical properties of spinal cord tissue. Given that a number of regenerative strategies aim to deliver cells and materials in the form of tissue-engineered therapies, understanding the biomechanical properties of host spinal cord tissue is important. We review the relevant biomechanical properties of spinal cord tissue and provide the baseline knowledge required to apply these important physical concepts to spinal cord tissue engineering.

Central nervous system (image)

MedlinePlus

... receive nerve impulses from the spinal cord and cranial nerves. The spinal cord contains the nerves that carry messages between the brain and the body. Spinal cord injury can occur when there is damage to the cells within the spinal cord or ...

The Correlation Between Recordable MEPs and Motor Function During Spinal Surgery for Resection of Thoracic Spinal Cord Tumor.

PubMed

Guo, LanJun; Li, Yan; Han, Ruquan; Gelb, Adrian W

2018-01-01

Motor evoked potentials (MEPs) are commonly used during surgery for spinal cord tumor resection. However, it can be difficult to record reliable MEPs from the muscles of the lower extremities during surgery in patients with preoperative weakness due to spinal cord compression. In this study, motor function of patients' lower extremities and their association with intraoperative MEP recording were compared. Patients undergoing thoracic spinal cord tumor resection were studied. Patients' motor function was checked immediately before the surgical procedure. MEP responses were recorded from the tibialis anterior and foot muscles, and the hand muscles were used as control. Electrical current with train of eight pulses, 200 to 500 V was delivered through 2 corkscrews placed at C3' and C4' sites. Anesthesia was maintained by total intravenous anesthesia using a combination of propofol and remifentanil after induction with intravenous propofol, remifentanil, and rocuronium. Rocuronium was not repeated. Bispectral Index was maintained between 40 to 50. From 178 lower limbs of 89 patients, myogenic MEPs could be recorded from 100% (105/105) of the patients with 5 of 5 motor strength in lower extremity; 90% (36/40) from the patients with 4/5 motor strength; only 25% (5/20) with 3/5; and 12.5% (1/8) with 2/5 motor strength; none (0/5) were able to be recorded if the motor strength was 1/5. The ability to record myogenic MEPs is closely associated with the patient's motor function. They are difficult to obtain if motor function is 3/5 motor strength in the lower extremity. They are almost impossible to record if motor function is worse than 3/5.

Image analysis of open-door laminoplasty for cervical spondylotic myelopathy: comparing the influence of cord morphology and spine alignment.

PubMed

Lin, Bon-Jour; Lin, Meng-Chi; Lin, Chin; Lee, Meei-Shyuan; Feng, Shao-Wei; Ju, Da-Tong; Ma, Hsin-I; Liu, Ming-Ying; Hueng, Dueng-Yuan

2015-10-01

Previous studies have identified the factors affecting the surgical outcome of cervical spondylotic myelopathy (CSM) following laminoplasty. Nonetheless, the effect of these factors remains controversial. It is unknown about the association between pre-operative cervical spinal cord morphology and post-operative imaging result following laminoplasty. The goal of this study is to analyze the impact of pre-operative cervical spinal cord morphology on post-operative imaging in patients with CSM. Twenty-six patients with CSM undergoing open-door laminoplasty were classified according to pre-operative cervical spine bony alignment and cervical spinal cord morphology, and the results were evaluated in terms of post-operative spinal cord posterior drift, and post-operative expansion of the antero-posterior dura diameter. By the result of study, pre-operative spinal cord morphology was an effective classification in predicting surgical outcome - patients with anterior convexity type, description of cervical spinal cord morphology, had more spinal cord posterior migration than those with neutral or posterior convexity type after open-door laminoplasty. Otherwise, the interesting finding was that cervical spine Cobb's angle had an impact on post-operative spinal cord posterior drift in patients with neutral or posterior convexity type spinal cord morphology - the degree of kyphosis was inversely proportional to the distance of post-operative spinal cord posterior drift, but not in the anterior convexity type. These findings supported that pre-operative cervical spinal cord morphology may be used as screening for patients undergoing laminoplasty. Patients having neutral or posterior convexity type spinal cord morphology accompanied with kyphotic deformity were not suitable candidates for laminoplasty. Copyright © 2015 Elsevier B.V. All rights reserved.

Spinal cord herniation following cervical meningioma excision: a rare clinical entity and review of literature.

PubMed

Aiyer, Siddharth N; Shetty, Ajoy Prasad; Kanna, Rishi; Maheswaran, Anupama; Rajasekaran, S

2016-05-01

Spinal cord herniation following surgery is an extremely uncommon clinical condition with very few reports in published literature. This condition usually occurs as a spontaneous idiopathic phenomenon often in the thoracic spine or following a scenario of post traumatic spinal cord/nerve root injury. Rarely has it been reported following spinal cord tumor surgery. To document a case of cervical spinal cord herniation as a late onset complication following spinal cord tumor surgery with an atypical presentation of monoparesis. Case report. We describe the clinical presentation, operative procedure, post operative outcome and review of literature of this rare clinical condition. A 57-year-old man presented with right upper limb monoparesis due to a spinal cord herniation 6 years after a cervical intradural meningioma excision. The patients underwent surgery to reduce the herniation and duroplasty with subsequent complete resolution of symptoms. Spinal cord herniation must be considered as differential diagnosis in scenarios of spinal cord tumor excision presenting with late onset neurological deficit. These cases may present as paraparesis, Brown-sequard syndrome and rarely as in our case as monoparesis.

Neurological function after total en bloc spondylectomy for thoracic spinal tumors.

PubMed

Murakami, Hideki; Kawahara, Norio; Demura, Satoru; Kato, Satoshi; Yoshioka, Katsuhito; Tomita, Katsuro

2010-03-01

Total en bloc spondylectomy (TES) for thoracic spinal tumors may in theory produce neurological dysfunction as a result of ischemic or mechanical damage to the spinal cord. Potential insults include preoperative embolization at 3 levels, intraoperative ligation of segmental arteries, nerve root ligation, and circumferential dural dissection. The purpose of this study was to assess neurological function after thoracic TES. The authors performed a retrospective review of 79 patients with thoracic-level spinal tumors that had been treated with TES between 1989 and 2006. Neurological function was retrospectively analyzed according to the Frankel grading system. Of the 79 cases, 26 involved primary tumors and 53 involved metastatic tumors. The number of excised vertebrae was 1 in 60 cases, 2 in 13, and >or= 3 in 6. The Frankel grade before surgery was B in 1 case, C in 16, D in 29, and E in 33. At the follow-up, the Frankel grade was C in 2 cases, D in 24, and E in 53. Of 46 cases with neurological deficits before surgery, neurological improvement of at least 1 Frankel grade was achieved in 25 cases (54.3%). Although the Frankel grade did not change in 21 patients, improvement in neurological symptoms within the same Frankel grade did occur in these patients. There were no cases of neurological deterioration. There was no neurological deterioration due to preoperative embolization, ligation of segmental arteries, or ligation of thoracic nerve roots. Each of the cases with preoperative neurological deficits showed improvement in neurological symptoms. Data in the current study clinically proved that TES is a safe operation with respect to spinal cord blood flow. In TES, the spinal cord is circumferentially decompressed and the spinal column is shortened. An increase in spinal cord blood flow due to spinal shortening in addition to decompression was considered to have brought about a resolution of neurological symptoms with TES.

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

DTIC Science & Technology

2013-10-01

of this award, we have found that stretching negatively influences locomotor function in animals with both acute (within days) and chronic (after 3...stretching is stopped, and both acute and chronic animals show a similar time course of recovery. Finally, in very preliminary studies, we have found...glove, data acquisition system and software work very well. The results demonstrate that forces about the ankle of the rat during therapeutic

IGF-1 delivery to CNS attenuates motor neuron cell death but does not improve motor function in type III SMA mice.

PubMed

Tsai, Li-Kai; Chen, Yi-Chun; Cheng, Wei-Cheng; Ting, Chen-Hung; Dodge, James C; Hwu, Wuh-Liang; Cheng, Seng H; Passini, Marco A

2012-01-01

The efficacy of administering a recombinant adeno-associated virus (AAV) vector encoding human IGF-1 (AAV2/1-hIGF-1) into the deep cerebellar nucleus (DCN) of a type III SMA mouse model was evaluated. High levels of IGF-1 transcripts and protein were detected in the spinal cord at 2 months post-injection demonstrating that axonal connections between the cerebellum and spinal cord were able to act as conduits for the viral vector and protein to the spinal cord. Mice treated with AAV2/1-hIGF-1 and analyzed 8 months later showed changes in endogenous Bax and Bcl-xl levels in spinal cord motor neurons that were consistent with IGF-1-mediated anti-apoptotic effects on motor neurons. However, although AAV2/1-hIGF-1 treatment reduced the extent of motor neuron cell death, the majority of rescued motor neurons were non-functional, as they lacked axons that innervated the muscles. Furthermore, treated SMA mice exhibited abnormal muscle fibers, aberrant neuromuscular junction structure, and impaired performance on motor function tests. These data indicate that although CNS-directed expression of IGF-1 could reduce motor neuron cell death, this did not translate to improvements in motor function in an adult mouse model of type III SMA. Copyright © 2011 Elsevier Inc. All rights reserved.

Measurement properties of the Spinal Cord Injury-Functional Index (SCI-FI) short forms.

PubMed

Heinemann, Allen W; Dijkers, Marcel P; Ni, Pengsheng; Tulsky, David S; Jette, Alan

2014-07-01

To evaluate the psychometric properties of the Spinal Cord Injury-Functional Index (SCI-FI) short forms (basic mobility, self-care, fine motor, ambulation, manual wheelchair, and power wheelchair) based on internal consistency; correlations between short forms banks, full item bank forms, and a 10-item computer adaptive test version; magnitude of ceiling and floor effects; and test information functions. Cross-sectional cohort study. Six rehabilitation hospitals in the United States. Individuals with traumatic spinal cord injury (N=855) recruited from 6 national Spinal Cord Injury Model Systems facilities. Not applicable. SCI-FI full item bank, 10-item computer adaptive test, and parallel short form scores. The SCI-FI short forms (with separate versions for individuals with paraplegia and tetraplegia) demonstrate very good internal consistency, group-level reliability, excellent correlations between short forms and scores based on the total item bank, and minimal ceiling and floor effects (except ceiling effects for persons with paraplegia on self-care, fine motor, and power wheelchair ability and floor effects for persons with tetraplegia on self-care, fine motor, and manual wheelchair ability). The test information functions are acceptable across the range of scores where most persons in the sample performed. Clinicians and researchers should consider the SCI-FI short forms when computer adaptive testing is not feasible. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Gene Expression Changes in the Injured Spinal Cord Following Transplantation of Mesenchymal Stem Cells or Olfactory Ensheathing Cells

PubMed Central

Torres-Espín, Abel; Hernández, Joaquim; Navarro, Xavier

2013-01-01

Transplantation of bone marrow derived mesenchymal stromal cells (MSC) or olfactory ensheathing cells (OEC) have demonstrated beneficial effects after spinal cord injury (SCI), providing tissue protection and improving the functional recovery. However, the changes induced by these cells after their transplantation into the injured spinal cord remain largely unknown. We analyzed the changes in the spinal cord transcriptome after a contusion injury and MSC or OEC transplantation. The cells were injected immediately or 7 days after the injury. The mRNA of the spinal cord injured segment was extracted and analyzed by microarray at 2 and 7 days after cell grafting. The gene profiles were analyzed by clustering and functional enrichment analysis based on the Gene Ontology database. We found that both MSC and OEC transplanted acutely after injury induce an early up-regulation of genes related to tissue protection and regeneration. In contrast, cells transplanted at 7 days after injury down-regulate genes related to tissue regeneration. The most important change after MSC or OEC transplant was a marked increase in expression of genes associated with foreign body response and adaptive immune response. These data suggest a regulatory effect of MSC and OEC transplantation after SCI regarding tissue repair processes, but a fast rejection response to the grafted cells. Our results provide an initial step to determine the mechanisms of action and to optimize cell therapy for SCI. PMID:24146830

[The Effectiveness of Abdominal Massage on Neurogenic Bowel Dysfunction in Patients With Spinal Cord Injury: A Systematic Review].

PubMed

Wu, Tzu-Jung; Lin, Chiu-Chu; Wang, Hsiu-Hung

2017-02-01

Neurogenic bowel dysfunction is a common comorbidity in spinal cord injury patients that may result in fecal incontinence. Abdominal massage is one intestinal training method that is used to improve bowel movement and defecation. To review the effectiveness of abdominal massage on neurogenic bowel dysfunction in patients with spinal cord injury. A systematic review of Chinese and English-language articles was performed in six databases using the following key words: spinal cord injury, abdominal massage, neurogenic bowel dysfunction, and bowel training. Relevant studies published prior to June 2016 that met the inclusion and exclusion criteria were selected. The Downs and Black scale was used to appraise the quality of each of the included studies. Eight studies were included in the final analysis. Four of these studies indicated that abdominal massage significantly improved bowel functions and the regularity and frequency of bowel movements. Although two of the studies indicated that abdominal massage significantly reduced the use of glycerin and laxatives, the remaining six did not. The eight studies earned respective quality scores ranging between 13 and 25. The current literature lacks consensus on the efficacy of abdominal massage in terms of improving bowel dysfunction in patients with spinal cord injuries. Future studies should use more stringent experimental designs such as randomized controlled studies to explore the correlations among massage time and frequency and bowel function improvements in order to provide guidelines for clinical care applications.

Spinal cord glioblastoma: 25years of experience from a single institution.

PubMed

Yanamadala, Vijay; Koffie, Robert M; Shankar, Ganesh M; Kumar, Jay I; Buchlak, Quinlan D; Puthenpura, Vidya; Frosch, Matthew P; Gudewicz, Thomas M; Borges, Lawrence F; Shin, John H

2016-05-01

Accounting for less than 0.2% of all glioblastomas, high grade gliomas of the spinal cord are very rare. Here, we discuss our approach to managing patients with high grade spinal cord glioma and review the literature on the subject. Six patients with high grade spinal cord gliomas who presented to our institution between 1990 and 2015 were reviewed. Each patient underwent subtotal surgical resection, with a subset receiving adjuvant chemotherapy and radiation. Our primary outcomes of interest were pre-operative and post-operative functional status. One year survival rate was 100%. All patients had stable or improved American Spine Injury Association score immediately after surgery, which was maintained at 3months in 83.3% of patients. Karnofsky Performance Status (KPS) was stable at 3month follow up in 50% of patients, but all had decreased KPS 1year after surgery. A subset of patients received post-operative radiation and chemotherapy with 0% tumor recurrence rate at 3months. We assessed the molecular profiles of tumors from two patients in our series and found that each had mutations in TP53, but had wildtype BRAF, IDH-1, and MGMT. Taken together, our data show that patients with high grade spinal cord gliomas have an excellent survival at 1year, but with some decline in functional status within this period. Further studies are needed to elucidate the natural history of the disease and to explore the role of adjuvant targeted molecular therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Primary Malignant Lymphoma in a Spinal Cord Presenting as an Epidural Mass with Myelopathy: A Case Report

PubMed Central

Cho, Jae-Hoon; Cho, Dae-Chul; Sung, Joo-Kyung

2012-01-01

We report the case of a 47-year-old man who presented with progressive paraparesis and sphincter changes over 2 weeks. Magnetic resonance imaging revealed a spinal epidural mass from T9 to L2. We performed a decompressive laminectomy and mass removal. The histopathology was consistent with a small lymphocytic lymphoma. No metastatic lesion was noted in the chest and abdomen-pelvic computerized tomography (CT) and positron emission tomography computerized tomography (PET-CT) scan. The final diagnosis was primary spinal lymphoma, so we performed chemotherapy combined with radiotherapy. At one year follow-up, he had no neurological deficit and no recurrence on neurologic and radiologic exams. Primary spinal cord lymphomas should be considered in the differential diagnosis of spinal cord tumors. Early surgical management is mandatory to achieve a recovery of neurologic function, especially if the patient has a neurological deficit. PMID:25983828

Acute spinal cord injury (SCI) transforms how GABA affects nociceptive sensitization.

PubMed

Huang, Yung-Jen; Lee, Kuan H; Murphy, Lauren; Garraway, Sandra M; Grau, James W

2016-11-01

Noxious input can sensitize pain (nociceptive) circuits within the spinal cord, inducing a lasting increase in spinal cord neural excitability (central sensitization) that is thought to contribute to chronic pain. The development of spinally-mediated central sensitization is regulated by descending fibers and GABAergic interneurons. The current study provides evidence that spinal cord injury (SCI) transforms how GABA affects nociceptive transmission within the spinal cord, recapitulating an earlier developmental state wherein GABA has an excitatory effect. In spinally transected rats, noxious electrical stimulation and inflammation induce enhanced mechanical reactivity (EMR), a behavioral index of nociceptive sensitization. Pretreatment with the GABA A receptor antagonist bicuculline blocked these effects. Peripheral application of an irritant (capsaicin) also induced EMR. Both the induction and maintenance of this effect were blocked by bicuculline. Cellular indices of central sensitization [c-fos expression and ERK phosphorylation (pERK)] were also attenuated. In intact (sham operated) rats, bicuculline had the opposite effect. Pretreatment with a GABA agonist (muscimol) attenuated nociceptive sensitization in intact, but not spinally injured, rats. The effect of SCI on GABA function was linked to a reduction in the Cl - transporter, KCC2, leading to a reduction in intracellular Cl - that would attenuate GABA-mediated inhibition. Pharmacologically blocking the KCC2 channel (with i.t. DIOA) in intact rats mimicked the effect of SCI. Conversely, a pharmacological treatment (bumetanide) that should increase intracellular Cl - levels blocked the effect of SCI. The results suggest that GABAergic neurons drive, rather than inhibit, the development of nociceptive sensitization after spinal injury. Copyright © 2016 Elsevier Inc. All rights reserved.

[Patient management in polytrauma with injuries of the cervical spine].

PubMed

Kohler, A; Friedl, H P; Käch, K; Stocker, R; Trentz, O

1994-04-01

Complex unstable cervical spine injuries in polytraumatized patients are stabilized ventro-dorsally in a two-stage procedure. The ventral stabilization is a day-one surgery with the goal to get primary stability for intensive care, early spinal decompression and protection against secondary damage of the spinal cord. The additional dorsal stabilization allows early functional treatment or in case of spinal cord lesions early neurorehabilitation. The combination of severe brain injury and unstable cervical spine injury is especially demanding concerning diagnostic and therapeutic procedures.

Acute intraparenchymal spinal cord injury in a cat due to high-rise syndrome.

PubMed

Cruz-Arámbulo, Robert; Nykamp, Stephanie

2012-03-01

A 9-year-old spayed female Bengal Red cat was evaluated for high-rise syndrome. The cat had paraplegia of the hind limbs, intact reflexes and pain perception, and hyperesthesia in the caudal thoracic area. Mentation, cranial nerve function, forelimb proprioceptive responses, and spinal reflexes were normal. There were no abnormalities on radiographs or computed tomography scan, but magnetic resonance imaging revealed a hyperintense intraparenchymal spinal cord lesion on T2-weighted and T2 fat saturation images.

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.

Sensorimotor Integration by Corticospinal System

PubMed Central

Moreno-López, Yunuen; Olivares-Moreno, Rafael; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

2016-01-01

The corticospinal (CS) tract is a complex system which targets several areas of the spinal cord. In particular, the CS descending projection plays a major role in motor command, which results from direct and indirect control of spinal cord pre-motor interneurons as well as motoneurons. But in addition, this system is also involved in a selective and complex modulation of sensory feedback. Despite recent evidence confirms that CS projections drive distinct segmental neural circuits that are part of the sensory and pre-motor pathways, little is known about the spinal networks engaged by the corticospinal tract (CST), the organization of CS projections, the intracortical microcircuitry, and the synaptic interactions in the sensorimotor cortex (SMC) that may encode different cortical outputs to the spinal cord. Here is stressed the importance of integrated approaches for the study of sensorimotor function of CS system, in order to understand the functional compartmentalization and hierarchical organization of layer 5 output neurons, who are key elements for motor control and hence, of behavior. PMID:27013985

Sensorimotor Integration by Corticospinal System.

PubMed

Moreno-López, Yunuen; Olivares-Moreno, Rafael; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

2016-01-01

The corticospinal (CS) tract is a complex system which targets several areas of the spinal cord. In particular, the CS descending projection plays a major role in motor command, which results from direct and indirect control of spinal cord pre-motor interneurons as well as motoneurons. But in addition, this system is also involved in a selective and complex modulation of sensory feedback. Despite recent evidence confirms that CS projections drive distinct segmental neural circuits that are part of the sensory and pre-motor pathways, little is known about the spinal networks engaged by the corticospinal tract (CST), the organization of CS projections, the intracortical microcircuitry, and the synaptic interactions in the sensorimotor cortex (SMC) that may encode different cortical outputs to the spinal cord. Here is stressed the importance of integrated approaches for the study of sensorimotor function of CS system, in order to understand the functional compartmentalization and hierarchical organization of layer 5 output neurons, who are key elements for motor control and hence, of behavior.

Murine neural crest stem cells and embryonic stem cell-derived neuron precursors survive and differentiate after transplantation in a model of dorsal root avulsion.

PubMed

Konig, Niclas; Trolle, Carl; Kapuralin, Katarina; Adameyko, Igor; Mitrecic, Dinko; Aldskogius, Hakan; Shortland, Peter J; Kozlova, Elena N

2017-01-01

Spinal root avulsion results in paralysis and sensory loss, and is commonly associated with chronic pain. In addition to the failure of avulsed dorsal root axons to regenerate into the spinal cord, avulsion injury leads to extensive neuroinflammation and degeneration of second-order neurons in the dorsal horn. The ultimate objective in the treatment of this condition is to counteract degeneration of spinal cord neurons and to achieve functionally useful regeneration/reconnection of sensory neurons with spinal cord neurons. Here we compare survival and migration of murine boundary cap neural crest stem cells (bNCSCs) and embryonic stem cells (ESCs)-derived, predifferentiated neuron precursors after their implantation acutely at the junction between avulsed dorsal roots L3-L6 and the spinal cord. Both types of cells survived transplantation, but showed distinctly different modes of migration. Thus, bNCSCs migrated into the spinal cord, expressed glial markers and formed elongated tubes in the peripheral nervous system (PNS) compartment of the avulsed dorsal root transitional zone (DRTZ) area. In contrast, the ESC transplants remained at the site of implantation and differentiated to motor neurons and interneurons. These data show that both stem cell types successfully survived implantation to the acutely injured spinal cord and maintained their differentiation and migration potential. These data suggest that, depending on the source of neural stem cells, they can play different beneficial roles for recovery after dorsal root avulsion. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Systematic Review of Theory-Based Interventions Aimed at Increasing Physical Activity in Individuals with Spinal Cord Injury

ERIC Educational Resources Information Center

Wilroy, Jereme; Knowlden, Adam

2016-01-01

Background: Approximately 200,000 individuals have a spinal cord injury (SCI) and more than 12,000 new cases are diagnosed each year in the United States. Lowered physical functioning caused by SCI often leads to a sedentary lifestyle, increasing risk for chronic diseases, secondary medical conditions, and lower quality of life. Purpose: The aim…

Improved axonal regeneration of transected spinal cord mediated by multichannel collagen conduits functionalized with neurotrophin-3 gene.

PubMed

Yao, L; Daly, W; Newland, B; Yao, S; Wang, W; Chen, B K K; Madigan, N; Windebank, A; Pandit, A

2013-12-01

Functionalized biomaterial scaffolds targeted at improving axonal regeneration by enhancing guided axonal growth provide a promising approach for the repair of spinal cord injury. Collagen neural conduits provide structural guidance for neural tissue regeneration, and in this study it is shown that these conduits can also act as a reservoir for sustained gene delivery. Either a G-luciferase marker gene or a neurotrophin-3-encoding gene, complexed to a non-viral, cyclized, PEGylated transfection vector, was loaded within a multichannel collagen conduit. The complexed genes were then released in a controlled fashion using a dual release system both in vitro and in vivo. For evaluation of their biological performance, the loaded conduits were implanted into the completely transected rat thoracic spinal cord (T8-T10). Aligned axon regeneration through the channels of conduits was observed one month post-surgery. The conduits delivering neurotrophin-3 polyplexes resulted in significantly increased neurotrophin-3 levels in the surrounding tissue and a statistically higher number of regenerated axons versus the control conduits (P<0.05). This study suggests that collagen neural conduits delivering a highly effective non-viral therapeutic gene may hold promise for repair of the injured spinal cord.

Delivery of Alginate Scaffold Releasing Two Trophic Factors for Spinal Cord Injury Repair

PubMed Central

Grulova, I.; Slovinska, L.; Blaško, J.; Devaux, S.; Wisztorski, M.; Salzet, M.; Fournier, I.; Kryukov, O.; Cohen, S.; Cizkova, D.

2015-01-01

Spinal cord injury (SCI) has been implicated in neural cell loss and consequently functional motor and sensory impairment. In this study, we propose an alginate -based neurobridge enriched with/without trophic growth factors (GFs) that can be utilized as a therapeutic approach for spinal cord repair. The bioavailability of key GFs, such as Epidermal Growth factor (EGF) and basic Fibroblast Growth Factor (bFGF) released from injected alginate biomaterial to the central lesion site significantly enhanced the sparing of spinal cord tissue and increased the number of surviving neurons (choline acetyltransferase positive motoneurons) and sensory fibres. In addition, we document enhanced outgrowth of corticospinal tract axons and presence of blood vessels at the central lesion. Tissue proteomics was performed at 3, 7 and 10 days after SCI in rats indicated the presence of anti-inflammatory factors in segments above the central lesion site, whereas in segments below, neurite outgrowth factors, inflammatory cytokines and chondroitin sulfate proteoglycan of the lectican protein family were overexpressed. Collectively, based on our data, we confirm that functional recovery was significantly improved in SCI groups receiving alginate scaffold with affinity-bound growth factors (ALG +GFs), compared to SCI animals without biomaterial treatment. PMID:26348665

The Extract of Roots of Sophora flavescens Enhances the Recovery of Motor Function by Axonal Growth in Mice with a Spinal Cord Injury.

PubMed

Tanabe, Norio; Kuboyama, Tomoharu; Kazuma, Kohei; Konno, Katsuhiro; Tohda, Chihiro

2015-01-01

Although axonal extension to reconstruct spinal tracts should be effective for restoring function after spinal cord injury (SCI), chondroitin sulfate proteoglycan (CSPG) levels increase at spinal cord lesion sites, and inhibit axonal regrowth. In this study, we found that the water extract of roots of Sophora flavescens extended the axons of mouse cortical neurons, even on a CSPG-coated surface. Consecutive oral administrations of S. flavescens extract to SCI mice for 31 days increased the density of 5-HT-positive axons at the lesion site and improved the motor function. Further, the active constituents in the S. flavescens extract were identified. The water and alkaloid fractions of the S. flavescens extract each exhibited axonal extension activity in vitro. LC/MS analysis revealed that these fractions mainly contain matrine and/or oxymatrine, which are well-known major compounds in S. flavescens. Matrine and oxymatrine promoted axonal extension on the CSPG-coated surface. This study is the first to demonstrate that S. flavescens extract, matrine, and oxymatrine enhance axonal growth in vitro, even on a CSPG-coated surface, and that S. flavescens extract improves motor function and increases axonal density in SCI mice.

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.

The international spinal cord injury endocrine and metabolic function basic data set.

PubMed

Bauman, W A; Biering-Sørensen, F; Krassioukov, A

2011-10-01

To develop the International Spinal Cord Injury (SCI) Endocrine and Metabolic Function Basic Data Set within the framework of the International SCI Data Sets that would facilitate consistent collection and reporting of basic endocrine and metabolic findings in the SCI population. International. The International SCI Endocrine and Metabolic Function Data Set was developed by a working group. The initial data set document was revised on the basis of suggestions from members of the Executive Committee of the International SCI Standards and Data Sets, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, American Spinal Injury Association (ASIA) Board, other interested organizations and societies, and individual reviewers. In addition, the data set was posted for 2 months on ISCoS and ASIA websites for comments. The final International SCI Endocrine and Metabolic Function Data Set contains questions on the endocrine and metabolic conditions diagnosed before and after spinal cord lesion. If available, information collected before injury is to be obtained only once, whereas information after injury may be collected at any time. These data include information on diabetes mellitus, lipid disorders, osteoporosis, thyroid disease, adrenal disease, gonadal disease and pituitary disease. The question of gonadal status includes stage of sexual development and that for females also includes menopausal status. Data will be collected for body mass index and for the fasting serum lipid profile. The complete instructions for data collection and the data sheet itself are freely available on the websites of ISCoS (http://www.iscos.org.uk) and ASIA (http://www.asia-spinalinjury.org).

Brain protection by methylprednisolone in rats with spinal cord injury.

PubMed

Chang, Chia-Mao; Lee, Ming-Hsueh; Wang, Ting-Chung; Weng, Hsu-Huei; Chung, Chiu-Yen; Yang, Jen-Tsung

2009-07-01

Traumatic spinal cord injury is clinically treated by high doses of methylprednisolone. However, the effect of methylprednisolone on the brain in spinal cord injury patients has been little investigated. This experimental study examined Bcl-2 and Bax protein expression and Nissl staining to evaluate an apoptosis-related intracellular signaling event and final neuron death, respectively. Spinal cord injury produced a significant apoptotic change and cell death not only in the spinal cord but also in the supraventricular cortex and hippocampal cornu ammonis 1 region in the rat brains. The treatment of methylprednisolone increased the Bcl-2/Bax ratio and prevented neuron death for 1-7 days after spinal cord injury. These findings suggest that rats with spinal cord injury show ascending brain injury that could be restricted through methylprednisolone management.

Neuromodulation of the lumbar spinal locomotor circuit.

PubMed

AuYong, Nicholas; Lu, Daniel C

2014-01-01

The lumbar spinal cord contains the necessary circuitry to independently drive locomotor behaviors. This function is retained following spinal cord injury (SCI) and is amenable to rehabilitation. Although the effectiveness of task-specific training and pharmacologic modulation has been repeatedly demonstrated in animal studies, results from human studies are less striking. Recently, lumbar epidural stimulation (EDS) along with locomotor training was shown to restore weight-bearing function and lower-extremity voluntary control in a chronic, motor-complete human SCI subject. Related animal studies incorporating EDS as part of the therapeutic regiment are also encouraging. EDS is emerging as a promising neuromodulatory tool for SCI. Copyright © 2014 Elsevier Inc. All rights reserved.

Clinical and imaging features of spinal cord type of neuro Behçet disease: A case report and systematic review.

PubMed

Liu, Hui-Miao; Dong, Ci; Zhang, Yong-Zhi; Tian, Ya-Yun; Chen, Hong-Xu; Zhang, Sai; Li, Na; Gu, Ping

2017-10-01

To investigate the clinical and MRI characteristics of spinal cord nerve Behçet's disease. One patient with spinal cord nerve Behçet's disease was admitted to our hospital at October 20, 2015. Spinal cord nerve Behçet's disease. Retrospective analysis was performed on such case as well as 16 cases of spinal cord nerve Behçet's disease reported in China or abroad. Seventeen cases of spinal cord type of neuro Behçet's disease include 13 men and 4 women, with an average age of onset of 34.8 years old. The mean time from Behçet's disease symptoms to spinal cord involvement were 10.8 years. The initial symptom in one case was spinal cord injury, and another 4 cases had a recurrence course. The most common performance of spinal cord injury was sensory disturbance (82.4%), following by weakness (76.5%), sphincter or sexual dysfunction (58.8%), and pain in back, backside of neck or lower chest (29.4%). The number of cells was slightly increased or the protein level was increased in cerebrospinal fluid test. And the water channel protein antibody and oligoclonal band of serum levels were all negative. The spinal cord injury involved more than 3 vertebral bodies in 10 cases, and involved more than half of spinal cord in sagittal plane in 8 cases. In acute stage, shock therapy with large dose of glucocorticoid was generally applied both in China and abroad. The clinical features of spinal cord nerve Behçet's disease were various, making it easily misdiagnosed. Longitudinal extensive transverse myelitis performs as a characteristic manifestation.

[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.

Periconal arterial anastomotic circle and posterior lumbosacral watershed zone of the spinal cord.

PubMed

Gailloud, Philippe; Gregg, Lydia; Galan, Peter; Becker, Daniel; Pardo, Carlos

2015-11-01

The existence of spinal cord watershed territories was suggested in the 1950s. Segmental infarcts within the junctional territories of adjacent radiculomedullary contributors and isolated spinal gray matter ischemia constitute two well-recognized types of watershed injury. This report describes the existence of another watershed territory related to the particular configuration of the spinal vasculature in the region of the conus medullaris. The anatomical bases underlying the concept of a posterior lumbosacral watershed zone are demonstrated with angiographic images obtained in a 16-year-old child. The clinical importance of this watershed zone is illustrated with MRI and angiographic data of three patients with a conus medullaris infarction. In all three cases of spinal ischemia an intersegmental artery providing a significant radiculomedullary contribution for the lower cord was compromised by a compressive mechanism responsible for decreased spinal cord perfusion (diaphragmatic crus syndrome in two cases, disk herniation in one). The ischemic injury, located at the junction of the anterior and posterior spinal artery territories along the dorsal aspect of the conus medullaris, was consistent with a watershed mechanism. This zone is at risk because of the caudocranial direction of flow within the most caudal segment of the posterior spinal arterial network which, from a functional standpoint, depends on the anterior spinal artery. The posterior thoracolumbar watershed zone of the spinal cord represents an area at increased risk of ischemic injury, particularly in the context of partial flow impairment related to arterial compression mechanisms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Spinal cord injury arising in anaesthesia practice.

PubMed

Hewson, D W; Bedforth, N M; Hardman, J G

2018-01-01

Spinal cord injury arising during anaesthetic practice is a rare event, but one that carries a significant burden in terms of morbidity and mortality. In this article, we will review the pathophysiology of spinal cord injury. We will then discuss injuries relating to patient position, spinal cord hypoperfusion and neuraxial techniques. The most serious causes of spinal cord injury - vertebral canal haematoma, spinal epidural abscess, meningitis and adhesive arachnoiditis - will be discussed in turn. For each condition, we draw attention to practical, evidence-based measures clinicians can undertake to reduce their incidence, or mitigate their severity. Finally, we will discuss transient neurological symptoms. Some cases of spinal cord injury during anaesthesia can be ascribed to anaesthesia itself, arising as a direct consequence of its conduct. The injury to a spinal nerve root by inaccurate and/or incautious needling during spinal anaesthesia is an obvious example. But in many cases, spinal cord injury during anaesthesia is not caused by, related to, or even associated with, the conduct of the anaesthetic. Surgical factors, whether direct (e.g. spinal nerve root damage due to incorrect pedicle screw placement) or indirect (e.g. cord ischaemia following aortic surgery) are responsible for a significant proportion of spinal cord injuries that occur concurrently with the delivery of regional or general anaesthesia. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

Transvertebral direct current stimulation paired with locomotor training in chronic spinal cord injury: A case study.

PubMed

Powell, Elizabeth Salmon; Carrico, Cheryl; Raithatha, Ravi; Salyers, Emily; Ward, Andrea; Sawaki, Lumy

2016-01-01

This double-blind, sham-controlled, crossover case study combined transvertebral direct current stimulation (tvDCS) and locomotor training on a robot-assisted gait orthosis (LT-RGO). Determine whether cathodal tvDCS paired with LT-RGO leads to greater changes in function and neuroplasticity than sham tvDCS paired with LT-RGO. University of Kentucky (UK) HealthCare Stroke and Spinal Cord Neurorehabilitation Research at HealthSouth Cardinal Hill Hospital. A single subject with motor incomplete spinal cord injury (SCI) participated in 24 sessions of sham tvDCS paired with LT-RGO before crossover to 24 sessions of cathodal tvDCS paired with LT-RGO. Functional outcomes were measured with 10 Meter Walk Test (10MWT), 6 Minute Walk Test (6MWT), Spinal Cord Independence Measure-III (SCIM-III) mobility component, lower extremity manual muscle test (MMT), and Berg Balance Scale (BBS). Corticospinal changes were assessed using transcranial magnetic stimulation. Improvement in 10MWT speed, SCIM-III mobility component, and BBS occurred with both conditions. 6MWT worsened after sham tvDCS and improved after cathodal tvDCS. MMT scores for both lower extremities improved following sham tvDCS but decreased following cathodal tvDCS. Corticospinal excitability increased following cathodal tvDCS but not sham tvDCS. These results suggest that combining cathodal tvDCS and LT-RGO may improve functional outcomes, increase corticospinal excitability, and possibly decrease spasticity. Randomized controlled trials are needed to confirm these conclusions. This publication was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1TR000117, and the HealthSouth Cardinal Hill Stroke and Spinal Cord Endowment (1215375670).

Spinal cord injury and women's sexual life: case-control study.

PubMed

Merghati-Khoei, E; Emami-Razavi, S H; Bakhtiyari, M; Lamyian, M; Hajmirzaei, S; Ton-Tab Haghighi, S; Korte, J E; Maasoumi, R

2017-03-01

Study design :This is a case-control study. The objective of this study was to estimate the magnitude of association between spinal cord injury (SCI) and women's quality of sexual life and sexual function. This study was conducted in the Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran. From the referral university-based clinics, we used simple random sampling to recruit 62 women: 31 women with SCI and 31 women without SCI. Socio-demographic and reproductive traits questionnaire, Sexual Quality of life-Female (SQOL-F), Female Sexual Function Index (FSFI) and Spinal Cord Independence Measure (SCIM) were completed using telephone and face-to-face interviews in the cases and controls. After univariate analyses, multivariate linear and proportional odds regression models were conducted to investigate the relation between SCI and women's quality of sexual life, as well as sexual function. The mean age of cases and controls was 35.42±6.51 and 33.77±4.02 years. Most women were high school-educated and housewives. Adjusting for probable confounders, the proportional odds regression model showed a significant relationship between the spinal cord injury (AOR=4.2, 95% CI: 1.8-9.2), non-college-educated (AOR=3.1, 95% CI: 1.2-5.9) and employed (AOR=1.8, 95% CI: 1.1-1.8) variables and being in one of the moderate or poor quality of life classes. Scores of SQOL-F and FSFI domains, except satisfaction, were significantly worse in cases versus controls (P<0.001). Although our participants showed low sexual dysfunction, they tended to report moderate to poor quality of sexual life. Our findings support the implication that sexual rehabilitation must be provided for women with SCI soon after injury.

Pronounced species divergence in corticospinal tract reorganization and functional recovery after lateralized spinal cord injury favors primates

PubMed Central

Friedli, Lucia; Rosenzweig, Ephron S.; Barraud, Quentin; Schubert, Martin; Dominici, Nadia; Awai, Lea; Nielson, Jessica L.; Musienko, Pavel; Nout-Lomas, Yvette; Zhong, Hui; Zdunowski, Sharon; Roy, Roland R.; Strand, Sarah C.; van den Brand, Rubia; Havton, Leif A.; Beattie, Michael S.; Bresnahan, Jacqueline C.; Bézard, Erwan; Bloch, Jocelyne; Edgerton, V. Reggie; Ferguson, Adam R.; Curt, Armin; Tuszynski, Mark H.; Courtine, Grégoire

2017-01-01

Experimental and clinical studies suggest that primate species exhibit greater recovery after lateralized compared to symmetrical spinal cord injuries. Although this observation has major implications for designing clinical trials and translational therapies, advantages in recovery of nonhuman primates over other species has not been shown statistically to date, nor have the associated repair mechanisms been identified. We monitored recovery in more than 400 quadriplegic patients and found that that functional gains increased with the laterality of spinal cord damage. Electrophysiological analyses suggested that corticospinal tract reorganization contributes to the greater recovery after lateralized compared with symmetrical injuries. To investigate underlying mechanisms, we modeled lateralized injuries in rats and monkeys using a lateral hemisection, and compared anatomical and functional outcomes with patients who suffered similar lesions. Standardized assessments revealed that monkeys and humans showed greater recovery of locomotion and hand function than rats. Recovery correlated with the formation of corticospinal detour circuits below the injury, which were extensive in monkeys, but nearly absent in rats. Our results uncover pronounced inter-species differences in the nature and extent of spinal cord repair mechanisms, likely resulting from fundamental differences in the anatomical and functional characteristics of the motor systems in primates versus rodents. Although rodents remain essential for advancing regenerative therapies, the unique response of the primate corticospinal tract after injury re-emphasizes the importance of primate models for designing clinically relevant treatments. PMID:26311729

Managing the stigma: Exploring body image experiences and self-presentation among people with spinal cord injury

PubMed Central

Bailey, K Alysse; Gammage, Kimberley L; van Ingen, Cathy; Ditor, David S

2016-01-01

Using modified constructivist grounded theory, the purpose of this study was to explore body image experiences in people with spinal cord injury. Nine participants (five women, four men) varying in age (21–63 years), type of injury (C3-T7; complete and incomplete), and years post-injury (4–36 years) took part in semi-structured in-depth interviews. The following main categories were found: appearance, weight concerns, negative functional features, impact of others, body disconnection, hygiene and incontinence, and self-presentation. Findings have implications for the health and well-being of those living with a spinal cord injury. PMID:28070405

[Dynamics of morphological changes in the spinal cord following exposure to non-ionizing microwave radiation].

PubMed

Belokrinitskiĭ, V S

1983-05-01

The structure of different portions (cervical, thoracic, lumbar, sacral and coccygeal) of the spinal cord were studied in the experiments on 50 animals with the use of the Nissl, Zimmermann, Cajal and other methods on days 1, 10, 20 and 30 after exposure to non-ionizing microwave radiation (NMI). Single exposure to NMI (wave length 12.6 cm, intensity 400-500 mW/cm2) for one hour (cats) or four hours (dogs) produces a severe distress of glial neurones and cells, which is marked by the appearance of dystrophic processes along the entire spinal cord. The disease progresses, leading to abnormalities of motor and other physiological functions of the body.

Training professionals' communication and motivation skills to improve spinal cord injury patients' satisfaction and clinical outcomes: Study protocol of the ESPELMA trial.

PubMed

Lusilla-Palacios, Pilar; Castellano-Tejedor, Carmina; Lucrecia-Ramírez-Garcerán; Navarro-Sanchís, José A; Rodríguez-Urrutia, Amanda; Parramon-Puig, Gemma; Valero-Ventura, Sergi; Cuxart-Fina, Ampar

2015-10-01

Acute spinal cord injury leaves patients severely impaired and generates high levels of psychological distress among them and their families, which can cause a less active role in rehabilitation, worse functional recovery, and less perceived satisfaction with the results. Additionally, rehabilitation professionals who deal with this psychological distress could ultimately experience higher stress and more risk of burnout. This article presents the study protocol of the ESPELMA project, aimed to train rehabilitation professionals in the clinical management of acute spinal cord injury-associated psychological distress, and to measure the impact of this training on the patients' perceived satisfaction with treatment. © The Author(s) 2013.

Beyond the Laboratory, Into the Clinic: What Dogs with Disk Disease Have Taught Us About Photobiomodulation for Spinal Cord Injury.

PubMed

Robinson, Narda G

2017-11-01

For spinal-cord-injured (SCI) patients, integrative medicine approaches such as photomedicine and acupuncture can renew hope and offer previously unrecognized ways to help regain function and improve quality of life. By understanding the mechanisms of action that these two modalities share, practitioners can better target specific attributes of spinal cord pathophysiology that are limiting recovery. Naturally occurring intervertebral disk disease (IVDD) in dogs affords unparalleled translational opportunities to develop treatment strategies involving photobiomodulation and acupuncture. Insights derived through clinical trials of dogs with IVDD have the potential to raise the standard of care for both human and canine SCI patients.

Effect of low-energy extracorporeal shock wave on vascular regeneration after spinal cord injury and the recovery of motor function.

PubMed

Wang, Lei; Jiang, Yuquan; Jiang, Zheng; Han, Lizhang

2016-01-01

Latest studies show that low-energy extracorporeal shock wave therapy (ESWT) can upregulate levels of vascular endothelial growth factor (VEGF). VEGF can ease nervous tissue harm after spinal cord injury (SCI). This study aims to explore whether low-energy ESWT can promote expression of VEGF, protect nervous tissue after SCI, and improve motor function. Ninety adult female rats were divided into the following groups: Group A (simple laminectomy), Group B (laminectomy and low-energy ESWT), Group C (spinal cord injury), and Group D (spinal cord injury and low-energy ESWT). Impinger was used to cause thoracic spinal cord injury. Low-energy ESWT was applied as treatment after injury three times a week, for 3 weeks. After SCI, the Basso, Beattie, and Bresnahan (BBB) scale was used to evaluate motor function over a period of 42 days at different time points. Hematoxylin and eosin (HE) staining was used to evaluate nerve tissue injury. Neuronal nuclear antigen (NeuN) staining was also used to evaluate loss of neurons. Polymerase chain reaction was used to detect messenger RNA (mRNA) expression of VEGF and its receptor fms-like tyrosine kinase 1 (Flt-1). Immunostaining was used to evaluate VEGF protein expression level in myeloid tissue. BBB scores of Groups A and B showed no significant result related to dyskinesia. HE and NeuN staining indicated that only using low-energy ESWT could not cause damage of nervous tissue in Group B. Recovery of motor function at 7, 35, and 42 days after SCI in Group D was better than that in Group C (P<0.05). Compared with Group C, number of NeuN-positive cells at 42 days after SCI increased significantly (P<0.05). The mRNA levels of VEGF and Flt-1 and VEGF expression at 7 days after SCI in Group D were significantly higher than those in Group C (P<0.05). Low-energy ESWT promotes expression of VEGF, decreases secondary damage of nerve tissue, and improves recovery of motor function. It can be regarded as one mode of clinical routine adjunctive therapy for spinal injury.

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.

AN IL-1 RECEPTOR ANTAGONIST BLOCKS A MORPHINE-INDUCED ATTENUATION OF LOCOMOTOR RECOVERY AFTER SPINAL CORD INJURY

PubMed Central

Hook, Michelle A.; Washburn, Stephanie N.; Moreno, Georgina; Woller, Sarah A.; Puga, Denise; Lee, Kuan H.; Grau, James W.

2010-01-01

Morphine is one of the most commonly prescribed medications for the treatment of chronic pain after a spinal cord injury (SCI). Despite widespread use, however, little is known about the secondary consequences of morphine use after SCI. Unfortunately, our previous studies show that administration of a single dose of morphine, in the acute phase of a moderate spinal contusion injury, significantly attenuates locomotor function, reduces weight gain, and produces symptoms of paradoxical pain (Hook et al., 2009). The current study focused on the cellular mechanisms that mediate these effects. Based on data from other models, we hypothesized that pro-inflammatory cytokines might play a role in the morphine-induced attenuation of function. Experiment 1 confirmed that systemic morphine (20 mg/kg) administered one day after a contusion injury significantly increased expression levels of spinal IL-1β 24 hrs later. Experiment 2 extended these findings, demonstrating that a single dose of morphine (90 µg, i.t.) applied directly onto the spinal cord increased expression levels of spinal IL-1β at both 30 min and 24 hrs after administration. Experiment 3 showed that administration of an interleukin-1 receptor antagonist (IL-1ra, i.t.) prior to intrathecal morphine (90 µg), blocked the adverse effects of morphine on locomotor recovery. Further, pre-treatment with 3 µg IL-1ra prevented the increased expression of at-level neuropathic pain symptoms that was observed 28 days later in the group treated with morphine-alone. However, the IL-1ra also had adverse effects that were independent of morphine. Treatment with the IL-1ra alone undermined recovery of locomotor function, potentiated weight loss and significantly increased tissue loss at the injury site. Overall, these data suggest that morphine disrupts a critical balance in concentrations of pro-inflammatory cytokines in the spinal cord, and this undermines recovery of function. PMID:20974246

Electroencephalographic evoked pain response is suppressed by spinal cord stimulation in complex regional pain syndrome: a case report.

PubMed

Hylands-White, Nicholas; Duarte, Rui V; Beeson, Paul; Mayhew, Stephen D; Raphael, Jon H

2016-12-01

Pain is a subjective response that limits assessment. The purpose of this case report was to explore how the objectivity of the electroencephalographic response to thermal stimuli would be affected by concurrent spinal cord stimulation. A patient had been implanted with a spinal cord stimulator for the management of complex regional pain syndrome of both hands for 8 years. Following ethical approval and written informed consent we induced thermal stimuli using the Medoc PATHWAY Pain & Sensory Evaluation System on the right hand of the patient with the spinal cord stimulator switched off and with the spinal cord stimulator switched on. The patient reported a clinically significant reduction in thermal induced pain using the numerical rating scale (71.4 % reduction) with spinal cord stimulator switched on. Analysis of electroencephalogram recordings indicated the occurrence of contact heat evoked potentials (N2-P2) with spinal cord stimulator off, but not with spinal cord stimulator on. This case report suggests that thermal pain can be reduced in complex regional pain syndrome patients with the use of spinal cord stimulation and offers objective validation of the reported outcomes with this treatment.

Lentiviral-mediated targeted NF-kappaB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat.

PubMed

Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

2007-04-01

Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor kappaB (NF-kappaB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-kappaB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-kappaB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-kappaB super- repressor IkappaBalpha resulted in an inhibition of the NF-kappaB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IkappaBalpha overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-kappaB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-kappaB pathway in the development of neuropathic pain after peripheral nerve injury.

Effects of the Post-Spinal Cord Injury Microenvironment on the Differentiation Capacity of Human Neural Stem Cells Derived from Induced Pluripotent Stem Cells.

PubMed

López-Serrano, Clara; Torres-Espín, Abel; Hernández, Joaquim; Alvarez-Palomo, Ana B; Requena, Jordi; Gasull, Xavier; Edel, Michael J; Navarro, Xavier

2016-10-01

Spinal cord injury (SCI) causes loss of neural functions below the level of the lesion due to interruption of spinal pathways and secondary neurodegenerative processes. The transplant of neural stem cells (NSCs) is a promising approach for the repair of SCI. Reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) is expected to provide an autologous source of iPSC-derived NSCs, avoiding the immune response as well as ethical issues. However, there is still limited information on the behavior and differentiation pattern of transplanted iPSC-derived NSCs within the damaged spinal cord. We transplanted iPSC-derived NSCs, obtained from adult human somatic cells, into rats at 0 or 7 days after SCI, and evaluated motor-evoked potentials and locomotion of the animals. We histologically analyzed engraftment, proliferation, and differentiation of the iPSC-derived NSCs and the spared tissue in the spinal cords at 7, 21, and 63 days posttransplant. Both transplanted groups showed a late decline in functional recovery compared to vehicle-injected groups. Histological analysis showed proliferation of transplanted cells within the tissue and that cells formed a mass. At the final time point, most grafted cells differentiated to neural and astroglial lineages, but not into oligodendrocytes, while some grafted cells remained undifferentiated and proliferative. The proinflammatory tissue microenviroment of the injured spinal cord induced proliferation of the grafted cells and, therefore, there are possible risks associated with iPSC-derived NSC transplantation. New approaches are needed to promote and guide cell differentiation, as well as reduce their tumorigenicity once the cells are transplanted at the lesion site.

Activity-specific aquatic therapy targeting gait for a patient with incomplete spinal cord injury.

PubMed

Wall, Tracy; Falvo, Lisa; Kesten, Adam

2017-04-01

Aquatic therapy can lead to improved mobility and health in individuals with various conditions. This case report looks at an activity-specific aquatic therapy targeting gait for a patient with incomplete spinal cord injury (iSCI). The patient participated in an individualized aquatic therapy program two times a week for 6 weeks. Assessment occurred prior to the intervention. There were two follow-up assessments after the intervention. Follow-up assessment 1 was completed within the same week as the final intervention. Follow-up assessment 2 was completed 4 weeks after the first follow-up to assess for carryover. Improvements that met minimal detectable change and minimal clinically important difference were noted in The Walking for Spinal Cord Injury Index-II, Spinal Cord Injury Functional Ambulation Index gait parameters, and gait speed. An activity-specific aquatic therapy program improved gait in a patient with iSCI. The properties of water create a practical environment for safe practice of skills. Further studies are warranted in large samples.

[Intramedullary spinal cord metastasis from gastric adenocarcinoma: Case report and review of literature].

PubMed

Pérez-Suárez, Javier; Barrio-Fernández, Patricia; Ibáñez-Plágaro, Francisco Javier; Ribas-Ariño, Teresa; Calvo-Calleja, Pablo; Mostaza-Saavedra, Antonio Luis

2016-01-01

Intramedullary spinal cord metastases are very rare and usually associated with lung or breast cancer, with gastric origin being exceptional. Their clinical onset tends to be faster than that of primary intramedullary tumours. The most common early symptoms of intramedullary spinal cord metastasis are motor deficit in one or more limbs, pain, sensory loss, and sphincter disturbances. The appearance of a rapidly progressive Brown-Séquard syndrome in an oncology patient should orientate the diagnosis of this condition. The prognosis is very poor, with a median survival of 4 months. However, recent research has shown that surgery could offer a slight benefit in survival and functionality. The case is reported of a 61-year-old man with an intramedullary spinal cord metastasis from a gastric carcinoma, as well as a literature review of this topic. It has been found that this case is the fourth one reported in the literature. Copyright © 2015. Published by Elsevier España.

Progressive Paraplegia from Spinal Cord Stimulator Lead Fibrotic Encapsulation: A Case Report.

PubMed

Benfield, Jon; Maknojia, Asif; Epstein, Franklin

2016-03-01

Ten years after placement of a spinal cord stimulator (SCS) and resolution of pain, this patient presented with progressive paraplegia, worsening thoracic radicular pain at the same dermatome level of the electrodes, and bowel and bladder incontinence. Computed tomographic myelogram confirmed thoracic spinal cord central canal stenosis at the level of electrodes. After removal of the fibrotic tissue and electrodes, the patient had resolution of his thoracic radicular pain and a return of his pre-SCS pain and minimal neurologic and functional return. To the authors' knowledge, no studies have been identified with thoracic SCS lead fibrosis in the United States causing permanent paraplegia. Only one other case has been reported in Madrid, Spain. Patients with SCS presenting with loss of pain relief, new-onset radicular or neuropathic pain in same dermatome(s) as SCS electrodes, worsening neuromuscular examination, or new bladder or bowel incontinence need to be evaluated for complications regarding SCS implantation causing spinal stenosis and subsequent cord compression to avoid permanent neurologic deficits.

Using Transcranial Magnetic Stimulation to Evaluate the Motor Pathways After an Intraoperative Spinal Cord Injury and to Predict the Recovery of Intraoperative Transcranial Electrical Motor Evoked Potentials: A Case Report.

PubMed

Grover, Helen J; Thornton, Rachel; Lutchman, Lennel N; Blake, Julian C

2016-06-01

The authors report a case of unilateral loss of intraoperative transcranial electrical motor evoked potentials (TES MEP) associated with a spinal cord injury during scoliosis correction and the subsequent use of extraoperative transcranial magnetic stimulation to monitor the recovery of spinal cord function. The authors demonstrate the absence of TES MEPs and absent transcranial magnetic stimulation responses in the immediate postoperative period, and document the partial recovery of transcranial magnetic stimulation responses, which corresponded to partial recovery of TES MEPs. Intraoperative TES MEPs were enhanced using spatial facilitation technique, which enabled the patient to undergo further surgery to stabilize the spine and correct her scoliosis. This case report supports evidence of the use of extraoperative transcranial magnetic stimulation to predict the presence of intraoperative TES responses and demonstrates the usefulness of spatial facilitation to monitor TES MEPs in a patient with a preexisting spinal cord injury.

Noninvasive Optical Monitoring of Spinal Cord Hemodynamics and Oxygenation after Acute Spinal Cord Injury

DTIC Science & Technology

2017-09-01

oxygen delivery and oxygen consumption . The oxygen portion of the Oxylite probe emits short pulses of blue LED light resulting in a fluorescent...Award Number: W81XWH-16-1-0602 TITLE: Noninvasive Optical Monitoring of Spinal Cord Hemodynamics and Oxygenation after Acute Spinal Cord Injury...COVERED 1 Sep 2016 - 31 Aug 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Noninvasive Optical Monitoring of Spinal Cord Hemodynamics and Oxygenation

Cervical Spinal Cord Atrophy Profile in Adult SMN1-Linked SMA

PubMed Central

El Mendili, Mohamed-Mounir; Lenglet, Timothée; Stojkovic, Tanya; Behin, Anthony; Guimarães-Costa, Raquel; Salachas, François; Meininger, Vincent; Bruneteau, Gaelle; Le Forestier, Nadine; Laforêt, Pascal; Lehéricy, Stéphane; Benali, Habib; Pradat, Pierre-François

2016-01-01

Purpose The mechanisms underlying the topography of motor deficits in spinal muscular atrophy (SMA) remain unknown. We investigated the profile of spinal cord atrophy (SCA) in SMN1-linked SMA, and its correlation with the topography of muscle weakness. Materials and Methods Eighteen SMN1-linked SMA patients type III/V and 18 age/gender-matched healthy volunteers were included. Patients were scored on manual muscle testing and functional scales. Spinal cord was imaged using 3T MRI system. Radial distance (RD) and cord cross-sectional area (CSA) measurements in SMA patients were compared to those in controls and correlated with strength and disability scores. Results CSA measurements revealed a significant cord atrophy gradient mainly located between C3 and C6 vertebral levels with a SCA rate ranging from 5.4% to 23% in SMA patients compared to controls. RD was significantly lower in SMA patients compared to controls in the anterior-posterior direction with a maximum along C4 and C5 vertebral levels (p-values < 10−5). There were no correlations between atrophy measurements, strength and disability scores. Conclusions Spinal cord atrophy in adult SMN1-linked SMA predominates in the segments innervating the proximal muscles. Additional factors such as neuromuscular junction or intrinsic skeletal muscle defects may play a role in more complex mechanisms underlying weakness in these patients. PMID:27089520

Identification of spinal 5-HT sub 3 receptors and their role in the modulation of nociceptive responses in the rat

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

Glaum, S.R.

1988-01-01

The project consisted of two related studies: (1) the characterization of serotonin binding sites in crude and purified synaptic membranes prepared from the rat spinal cord, and (2) the association of serotonin binding sites with functional 5-HT receptor responses in the modulation of nociceptive information at the level of the spinal cord. The first series of experiments involved the preparation of membranes from the dorsal and ventral halves of the rat spinal cord and the demonstration of specific ({sup 3}H)serotonin binding to these membranes. High affinity binding sites which conformed to the 5-HT{sub 3} subtype were identified in dorsal, butmore » not ventral spinal cord synaptic membranes. These experiments also confirmed the presence of high affinity ({sup 3}H)5-HT binding sites in dorsal spinal cord synaptic membranes of the 5-HT{sub 1} subtype. The second group of studies demonstrated the ability of selective 5-HT{sub 3} antagonists to inhibit the antinociceptive response to intrathecally administered 5-HT, as measured by a change in tail flick and hot plate latencies. Intrathecal pretreatment with the selective 5-HT{sub 3} antagonists ICS 205-930 or MDL 72222 abolished the antinociceptive effects of 5-HT. Furthermore, the selective 5-HT{sub 3} agonist 2-methyl-5-HT mimicked the antinociceptive effects of 5-HT.« less

Meningocele repair - series (image)

MedlinePlus

... containing a portion of the spinal cord membrane (meninges), spinal fluid, and a portion of spinal cord ... The spinal cord is covered with the membranes (meninges) and the skin is closed over the protruding ...

Part 1: recognizing neonatal spinal cord injury.

PubMed

Brand, M Colleen

2006-02-01

Neonatal spinal cord injury can occur in utero, as well as after either a difficult delivery or a nontraumatic delivery. Spinal cord injury can also be related to invasive nursery procedures or underlying neonatal pathology. Early clinical signs of spinal cord injury that has occurred in utero or at delivery includes severe respiratory compromise and profound hypotonia. Knowledge of risk factors and awareness of symptoms is required for early recognition and appropriate treatment. This article reviews the embryological development of the spinal column highlighting mechanisms of injury and identifying underlying factors that increase the risk of spinal cord injury in newborns. Signs and symptoms of injury, cervical spine immobilization, and the differential diagnosis are discussed. Nursing implications, general prognosis, and research in spinal cord injury are provided.

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.

Effects of aquatic exercise on physical function and fitness among people with spinal cord injury: A systematic review.

PubMed

Li, Chunxiao; Khoo, Selina; Adnan, Athirah

2017-03-01

The aim of this review is to synthesize the evidence on the effects of aquatic exercise interventions on physical function and fitness among people with spinal cord injury. Six major databases were searched from inception till June 2015: MEDLINE, CINAHL, EMBASE, PsychInfo, SPORTDiscus, and Cochrane Center Register of Controlled Trials. Two reviewers independently rated methodological quality using the modified Downs and Black Scale and extracted and synthesized key findings (i.e., participant characteristics, study design, physical function and fitness outcomes, and adverse events). Eight of 276 studies met the inclusion criteria, of which none showed high research quality. Four studies assessed physical function outcomes and 4 studies evaluated aerobic fitness as outcome measures. Significant improvements on these 2 outcomes were generally found. Other physical or fitness outcomes including body composition, muscular strength, and balance were rarely reported. There is weak evidence supporting aquatic exercise training to improve physical function and aerobic fitness among adults with spinal cord injury. Suggestions for future research include reporting details of exercise interventions, evaluating other physical or fitness outcomes, and improving methodological quality.

Combined polymer-curcumin conjugate and ependymal progenitor/stem cell treatment enhances spinal cord injury functional recovery.

PubMed

Requejo-Aguilar, Raquel; Alastrue-Agudo, Ana; Cases-Villar, Marta; Lopez-Mocholi, Eric; England, Richard; Vicent, María J; Moreno-Manzano, Victoria

2017-01-01

Spinal cord injury (SCI) suffers from a lack of effective therapeutic strategies. Animal models of acute SCI have provided evidence that transplantation of ependymal stem/progenitor cells of the spinal cord (epSPCs) induces functional recovery, while systemic administration of the anti-inflammatory curcumin provides neuroprotection. However, functional recovery from chronic stage SCI requires additional enhancements in available therapeutic strategies. Herein, we report on a combination treatment for SCI using epSPCs and a pH-responsive polymer-curcumin conjugate. The incorporation of curcumin in a pH-responsive polymeric carrier mainchain, a polyacetal (PA), enhances blood bioavailability, stability, and provides a means for highly localized delivery. We find that PA-curcumin enhances neuroprotection, increases axonal growth, and can improve functional recovery in acute SCI. However, when combined with epSPCs, PA-curcumin also enhances functional recovery in a rodent model of chronic SCI. This suggests that combination therapy may be an exciting new therapeutic option for the treatment of chronic SCI in humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

Survey of spinal cord injury-induced neurogenic bladder studies using the Web of Science.

PubMed

Zou, Benjing; Zhang, Yongli; Li, Yucheng; Wang, Zantao; Zhang, Ping; Zhang, Xiyin; Wang, Bingdong; Long, Zhixin; Wang, Feng; Song, Guo; Wang, Yan

2012-08-15

To identify global trends in research on spinal cord injury-induced neurogenic bladder, through a bibliometric analysis using the Web of Science. We performed a bibliometric analysis of studies on spinal cord injury-induced neurogenic bladder using the Web of Science. Data retrieval was performed using key words "spinal cord injury", "spinal injury", "neurogenic bladder", "neuropathic bladder", "neurogenic lower urinary tract dysfunction", "neurogenic voiding dysfunction", "neurogenic urination disorder" and "neurogenic vesicourethral dysfunction". (a) published peer-reviewed articles on spinal cord injury-induced neurogenic bladder indexed in the Web of Science; (b) type of articles: original research articles and reviews; (c) year of publication: no limitation. (a) articles that required manual searching or telephone access; (b) Corrected papers and book chapters. (1) Annual publication output; (2) distribution according to journals; (3) distribution according to subject areas; (4) distribution according to country; (5) distribution according to institution; and (6) top cited publications. There were 646 research articles addressing spinal cord injury-induced neurogenic bladder in the Web of Science. Research on spinal cord injury-induced neurogenic bladder was found in the Science Citation Index-Expanded as of 1946. The United States, Ireland and Switzerland were the three major countries contributing to studies in spinal cord injury-induced neurogenic bladder in the 1970s. However, in the 1990s, the United States, the United Kingdom, the Netherlands, Germany and Japan published more papers on spinal cord injury-induced neurogenic bladder than Switzerland, and Ireland fell off the top ten countries list. In this century, the United States ranks first in spinal cord injury-induced neurogenic bladder studies, followed by France, the United Kingdom, Germany, Switzerland and Japan. Subject categories including urology, nephrology and clinical neurology, as well as rehabilitation, are represented in spinal cord injury-induced neurogenic bladder studies. From our analysis of the literature and research trends, we conclude that spinal cord injury-induced neurogenic bladder is a hot topic that will continue to generate considerable research interest in the future.

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

Balance and coordination training, but not endurance training, enhances synaptophysin and neurotrophin-3 immunoreactivity in the lumbar spinal cord after sciatic nerve crush.

PubMed

Bonetti, Leandro Viçosa; Ilha, Jocemar; Schneider, Ana Paula Krauthein; Barbosa, Silvia; Faccioni-Heuser, Maria Cristina

2016-04-01

Numerous rehabilitation treatments have been shown to be useful for peripheral and central restoration after (PNI). After sciatic nerve crush, we investigated 4 weeks of endurance training (ET) and balance and coordination training (BCT) with sciatic function index, hind-paw stride length, and spinal cord dorsal horn synaptophysin and neurotrophin-3 immunoreactivity. Our results demonstrated no significant differences between the non-trained (NT), ET, and BCT groups in sciatic functional index, and in stride-length analysis, but the ET showed higher values compared with the NT group. Synaptophysin immunoreactivity was higher in the BCT group compared with the NT group, and neurotrophin-3 immunoreactivity in the BCT group was greater compared with the other groups. BCT can positively affect spinal cord plasticity after a (PNI), and these modifications are important in the rehabilitation process. © 2015 Wiley Periodicals, Inc.

Patients, doctors, and therapists perceptions of professional roles in spinal cord injury rehabilitation: do they agree?

PubMed

Pellatt, Glynis Collis

2007-03-01

Spinal cord injury is a devastating condition, requiring extensive rehabilitation from a range of health care professionals. However, it is unclear if patients view the professionals' input into their rehabilitation in the same way as those professionals. This paper presents findings from a qualitative study into patient participation in spinal cord injury rehabilitation. The aim of the part of the study reported here was to identify whether there is agreement between health care professionals and patients perceptions of professional roles in spinal cord injury rehabilitation. Results are presented from semi-structured interviews conducted with five doctors, five physiotherapists, three occupational therapists and 20 patients in a spinal cord injury unit in England. Findings suggest considerable agreement between professionals and patients about the role those professionals play in their rehabilitation. Physiotherapists are perceived to be key to rehabilitation, occupational therapists focus on hand function but physiotherapists and occupational therapists complement each other. Doctors coordinate the team yet reduce their input as patients move out of the acute phase into rehabilitation. There are some tensions but the early input of these professionals into patients' rehabilitation may help to develop understanding of roles. Congruence between patients and professionals may mean that patients have realistic expectations and encourage a more equal relationship between them.

X-ray phase-contrast computed tomography visualizes the microstructure and degradation profile of implanted biodegradable scaffolds after spinal cord injury

PubMed Central

Takashima, Kenta; Hoshino, Masato; Uesugi, Kentaro; Yagi, Naoto; Matsuda, Shojiro; Nakahira, Atsushi; Osumi, Noriko; Kohzuki, Masahiro; Onodera, Hiroshi

2015-01-01

Tissue engineering strategies for spinal cord repair are a primary focus of translational medicine after spinal cord injury (SCI). Many tissue engineering strategies employ three-dimensional scaffolds, which are made of biodegradable materials and have microstructure incorporated with viable cells and bioactive molecules to promote new tissue generation and functional recovery after SCI. It is therefore important to develop an imaging system that visualizes both the microstructure of three-dimensional scaffolds and their degradation process after SCI. Here, X-ray phase-contrast computed tomography imaging based on the Talbot grating interferometer is described and it is shown how it can visualize the polyglycolic acid scaffold, including its microfibres, after implantation into the injured spinal cord. Furthermore, X-ray phase-contrast computed tomography images revealed that degradation occurred from the end to the centre of the braided scaffold in the 28 days after implantation into the injured spinal cord. The present report provides the first demonstration of an imaging technique that visualizes both the microstructure and degradation of biodegradable scaffolds in SCI research. X-ray phase-contrast imaging based on the Talbot grating interferometer is a versatile technique that can be used for a broad range of preclinical applications in tissue engineering strategies. PMID:25537600

Changes in Locomotor Muscle Activity After Treadmill Training in Subjects With Incomplete Spinal Cord Injury

PubMed Central

Gorassini, Monica A.; Norton, Jonathan A.; Nevett-Duchcherer, Jennifer; Roy, Francois D.; Yang, Jaynie F.

2009-01-01

Intensive treadmill training after incomplete spinal cord injury can improve functional walking abilities. To determine the changes in muscle activation patterns that are associated with improvements in walking, we measured the electromyography (EMG) of leg muscles in 17 individuals with incomplete spinal cord injury during similar walking conditions both before and after training. Specific differences were observed between subjects that eventually gained functional improvements in overground walking (responders), compared with subjects where treadmill training was ineffective (nonresponders). Although both groups developed a more regular and less clonic EMG pattern on the treadmill, it was only the tibialis anterior and hamstring muscles in the responders that displayed increases in EMG activation. Likewise, only the responders demonstrated decreases in burst duration and cocontraction of proximal (hamstrings and quadriceps) muscle activity. Surprisingly, the proximal muscle activity in the responders, unlike nonresponders, was three- to fourfold greater than that in uninjured control subjects walking at similar speeds and level of body weight support, suggesting that the ability to modify muscle activation patterns after injury may predict the ability of subjects to further compensate in response to motor training. In summary, increases in the amount and decreases in the duration of EMG activity of specific muscles are associated with functional recovery of walking skills after treadmill training in subjects that are able to modify muscle activity patterns following incomplete spinal cord injury. PMID:19073799

Anterior spinal artery syndrome. Paraplegia following segmental ischaemic injury to the spinal cord after oesophagectomy.

PubMed

Djurberg, H; Haddad, M

1995-04-01

A case of unexpected paraplegia after oesophageal resection under general anaesthesia combined with epidural analgesia and intra-operative intercostal block is described. Patients with compromised cardiovascular and respiratory function undergoing thoracic or major abdominal surgery can benefit significantly intra-operatively from a combination of general anaesthesia and regional analgesia. The continued use of regional analgesia into the postoperative period offers even more advantages. General anaesthesia administered before regional analgesia may, however, mask complications related to the regional technique and delay the instigation of corrective measures. The blood supply to the anterior part of the spinal cord, through the artery of Adamkiewicz, may be impaired intra-operatively leading to neurological sequelae known as the anterior spinal artery syndrome, characterised by loss of motor function with intact or partially intact sensory function. Patients at risk of developing the syndrome can be identified pre-operatively.

[A robotic system for gait re-education in patients with an incomplete spinal cord injury].

PubMed

Esclarín-De Ruz, A; Alcobendas-Maestro, M; Casado-López, R; Muñoz-Gonzalez, A; Florido-Sánchez, M A; González-Valdizán, E

A spinal cord injury involves the loss or alteration of motor patterns in walking, the recovery of which depends partly on the rearrangement of the preserved neural circuits. AIM. To evaluate the changes that take place in the gait of patients with incomplete spinal cord injuries who were treated with a robotic walking system in association with conventional therapy. The study conducted was an open-label, prospective, descriptive trial with statistical inference in patients with C2-L3 spinal cord injuries that were classified as degrees C and D according to the American Spinal Injury Association (ASIA) scale. The variables that were analysed on the first and the last day of the study were: number of walkers, 10-m gait test, the Walking Index for Spinal Cord Injury scale revision, technical aids, muscle balance in the lower limbs, locomotor subscale of the measure of functional independence, modified Ashworth scale for spasticity and the visual analogue scale for pain. At the end, data were recorded from the impression of change scale. The analysis was conducted by means of Student's t, chi squared and Pearson's correlation; p < or = 0.05. Forty-five patients, with a mean age of 44 +/- 14.3 years, finished the study; 76% were males, injury was caused by trauma in 58% of cases, and the time of progression was 139 +/- 70 days. Statistically significant increases were observed in the number of subjects capable of walking, walking speed, less need for technical aids, strength in the lower limbs and independence in activities of daily living. Treatment using the robotic system in association with conventional therapy improves walking capacity in patients with incomplete spinal cord injuries.

Exploration of Spinal Cord Aging-Related Proteins Using a Proteomics Approach.

PubMed

Kamiya, Koshiro; Furuya, Takeo; Hashimoto, Masayuki; Mannoji, Chikato; Inada, Taigo; Ota, Mitsutoshi; Maki, Satoshi; Ijima, Yasushi; Saito, Junya; Kitamura, Mitsuhiro; Ohtori, Seiji; Orita, Sumihisa; Inage, Kazuhide; Yamazaki, Masashi; Koda, Masao

2017-01-01

How aging affects the spinal cord at a molecular level is unclear. The aim of this study was to explore spinal cord aging-related proteins that may be involved in pathological mechanisms of age-related changes in the spinal cord. Spinal cords of 2-year-old and 8-week-old female Sprague-Dawley rats were dissected from the animals. Protein samples were subjected to 2-dimentional polyacrylamide gel electrophoresis followed by mass spectrometry. Screened proteins were further investigated with immunohistochemistry and Western blotting. Among the screened proteins, we selected α-crystallin B-subunit (αB-crystallin) and peripherin for further investigation because these proteins were previously reported to be related to central nervous system pathologies. Immunohistochemistry and Western blotting revealed significant upregulation of αB-crystallin and peripherin expression in aged rat spinal cord. Further exploration is needed to elucidate the precise mechanism and potential role of these upregulated proteins in spinal cord aging processes.

Spinal Cord Lesions in Congenital Toxoplasmosis Demonstrated with Neuroimaging, Including Their Successful Treatment in an Adult.

PubMed

Burrowes, Delilah; Boyer, Kenneth; Swisher, Charles N; Noble, A Gwendolyn; Sautter, Mari; Heydemann, Peter; Rabiah, Peter; Lee, Daniel; McLeod, Rima

2012-03-01

Neuroimaging studies for persons in the National Collaborative Chicago-Based Congenital Toxoplasmosis Study (NCCCTS) with symptoms and signs referable to the spinal cord were reviewed. Three infants had symptomatic spinal cord lesions, another infant a Chiari malformation, and another infant a symptomatic peri-spinal cord lipoma. One patient had an unusual history of prolonged spinal cord symptoms presenting in middle age. Neuroimaging was used to establish her diagnosis and response to treatment. This 43 year-old woman with congenital toxoplasmosis developed progressive leg spasticity, weakness, numbness, difficulty walking, and decreased visual acuity and color vision without documented re-activation of her chorioretinal disease. At 52 years of age, spinal cord lesions in locations correlating with her symptoms and optic atrophy were diagnosed with 3 Tesla MRI scan. Treatment with pyrimethamine and sulfadiazine decreased her neurologic symptoms, improved her neurologic examination, and resolved her enhancing spinal cord lesions seen on MRI.

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.

Regional variations and age-related changes in arginine metabolism in the rat brain stem and spinal cord.

PubMed

Jing, Y; Fleete, M S; Collie, N D; Zhang, H; Liu, P

2013-11-12

Accumulating evidence suggests that the metabolism of l-arginine, a metabolically versatile amino acid, is critically involved in the aging process. The present study compared the activity and protein expression of nitric oxide synthase (NOS) and arginase, and the levels of l-arginine and its eight down-stream metabolites in the brain stem (pons and medulla) and the cervical spinal cord in 3- (young) and 22- (aged) month-old male Sprague-Dawley rats. Total NOS activity was significantly reduced with age in the spinal cord (but not brain stem), and there were no age-related changes in arginase activity in both regions. Western blot revealed decreased protein expression of endothelial NOS, but not neuronal NOS, with age in both regions. Furthermore, there were significantly decreased l-arginine, glutamate, GABA and spermine levels and increased putrescine and spermidine levels with age in both regions. Although the absolute concentrations of l-arginine and six metabolites were significantly different between the brain stem and spinal cord in both age groups, there were similar clusters between l-arginine and its three main metabolites (l-citrulline, l-ornithine and agmatine) in both regions, which changed as a function of age. These findings, for the first time, demonstrate the regional variations and age-related changes in arginine metabolism in the rat brain stem and spinal cord. Future research is required to understand the functional significance of these changes and the underlying mechanisms. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Music modulation of pain perception and pain-related activity in the brain, brain stem, and spinal cord: a functional magnetic resonance imaging study.

PubMed

Dobek, Christine E; Beynon, Michaela E; Bosma, Rachael L; Stroman, Patrick W

2014-10-01

The oldest known method for relieving pain is music, and yet, to date, the underlying neural mechanisms have not been studied. Here, we investigate these neural mechanisms by applying a well-defined painful stimulus while participants listened to their favorite music or to no music. Neural responses in the brain, brain stem, and spinal cord were mapped with functional magnetic resonance imaging spanning the cortex, brain stem, and spinal cord. Subjective pain ratings were observed to be significantly lower when pain was administered with music than without music. The pain stimulus without music elicited neural activity in brain regions that are consistent with previous studies. Brain regions associated with pleasurable music listening included limbic, frontal, and auditory regions, when comparing music to non-music pain conditions. In addition, regions demonstrated activity indicative of descending pain modulation when contrasting the 2 conditions. These regions include the dorsolateral prefrontal cortex, periaqueductal gray matter, rostral ventromedial medulla, and dorsal gray matter of the spinal cord. This is the first imaging study to characterize the neural response of pain and how pain is mitigated by music, and it provides new insights into the neural mechanism of music-induced analgesia within the central nervous system. This article presents the first investigation of neural processes underlying music analgesia in human participants. Music modulates pain responses in the brain, brain stem, and spinal cord, and neural activity changes are consistent with engagement of the descending analgesia system. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

21 CFR 882.5880 - Implanted spinal cord stimulator for pain relief.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted spinal cord stimulator for pain relief. 882.5880 Section 882.5880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Implanted spinal cord stimulator for pain relief. (a) Identification. An implanted spinal cord stimulator...

76 FR 71623 - Agency Information Collection (Spinal Cord Injury Patient Care Survey) Under OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-18

... Collection (Spinal Cord Injury Patient Care Survey) Under OMB Review AGENCY: Veterans Benefits Administration... INFORMATION: Title: Spinal Cord Injury Patient Care Survey, VA Form 10-0515. OMB Control Number: OMB Control... 10-0515 will be used to determine spinal cord patients' satisfaction with VA rehabilitation and...

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.

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

Effects of pacing-induced myocardial stress and spinal cord stimulation on whole body and cardiac norepinephrine spillover.

PubMed

Norrsell, H; Eliasson, T; Mannheimer, C; Augustinsson, L E; Bergh, C H; Andersson, B; Waagstein, F; Friberg, P

1997-12-01

Spinal cord stimulation has been used in the treatment of intractable angina pectoris since the beginning of the 1980s. This study was designed to investigate whether the documented anti-ischaemic effects of spinal cord stimulation are mediated through a decrease in sympathetic activity. Ten patients with a spinal cord stimulator implanted as anti-anginal treatment were included in the study. Atrial pacing until the patient experienced moderate angina was performed and after 50 min rest the procedure was repeated during spinal cord stimulation. Total body and cardiac norepinephrine spillover was calculated and the former was found to have increased during pacing (47%, P = 0.02). When spinal cord stimulation was applied, total body norepinephrine spillover decreased at a comparable pacing rate (18%, P = 0.02). Cardiac norepinephrine spillover was not affected during the procedure. The results of this study indicate that the anti-ischaemic effect of spinal cord stimulation is not due to reduced cardiac sympathetic activity. However, spinal cord stimulation decreases overall sympathetic activity which may benefit the heart, possibly by reducing oxygen demand.

Parasitic twin--a supernumerary limb associated with spinal malformations. A case report.

PubMed

Sahlu, Abat; Mesfin, Brook; Tirsit, Abenezer; Debebe, Tequam; Wester, Knut

2016-03-01

We describe a case of rachipagus parasitic twin with spinal cord malformations (lipomyelomeningocele and tethered cord) in a 7-month-old Ethiopian infant. The parasitic mass had a well-formed foot, ankle and lower leg and a small sinus that resembled an anus. Magnetic resonance imaging scans revealed spinal malformations including a distal syringohydromyelia. The mass was successfully resected and the dural attachment was closed. Histopathological examination confirmed the diagnosis. Postoperatively, the child had unchanged, intact neurological function in both lower limbs. Almost all rachipagus parasitic twins are associated with spinal malformations. They should, therefore, be operated on by surgeons experienced in myelomeningocele surgery.

Intraoperative monitoring of somatosensory-evoked potential in the spinal cord rectification operation by means of wavelet analysis

NASA Astrophysics Data System (ADS)

Liu, W.; Du, M. H.; Chan, Francis H. Y.; Lam, F. K.; Luk, D. K.; Hu, Y.; Fung, Kan S. M.; Qiu, W.

1998-09-01

Recently there has been a considerable interest in the use of a somatosensory evoked potential (SEP) for monitoring the functional integrity of the spinal cord during surgery such as spinal scoliosis. This paper describes a monitoring system and signal processing algorithms, which consists of 50 Hz mains filtering and a wavelet signal analyzer. Our system allows fast detection of changes in SEP peak latency, amplitude and signal waveform, which are the main parameters of interest during intra-operative procedures.

Curcumin Increase the Expression of Neural Stem/Progenitor Cells and Improves Functional Recovery after Spinal Cord Injury

PubMed Central

Bang, Woo-Seok; Kim, Kyoung-Tae; Seo, Ye Jin; Cho, Dae-Chul; Sung, Joo-Kyung; Kim, Chi Heon

2018-01-01

Objective To investigates the effect of curcumin on proliferation of spinal cord neural stem/progenitor cells (SC-NSPCs) and functional outcome in a rat spinal cord injury (SCI) model. Methods Sixty adult male Sprague-Dawley rats were randomly and blindly allocated into three groups (sham control group; curcumin treated group after SCI; vehicle treated group after SCI). Functional recovery was evaluated by the Basso, Beattie, and Bresnahan (BBB) scale during 6 weeks after SCI. The expression of SC-NSPC proliferation and astrogliosis were analyzed by nestin/Bromodeoxyuridine (BrdU) and Glial fibrillary acidic protein (GFAP) staining. The injured spinal cord was then examined histologically, including quantification of cavitation. Results The BBB score of the SCI-curcumin group was better than that of SCI-vehicle group up to 14 days (p<0.05). The co-immunoreactivity of nestin/BrdU in the SCI-curcumin group was much higher than that of the SCI-vehicle group 1 week after surgery (p<0.05). The GFAP immunoreactivity of the SCI-curcumin group was remarkably lower than that of the SCI-vehicle group 4 weeks after surgery (p<0.05). The lesion cavity was significantly reduced in the curcumin group as compared to the control group (p<0.05). Conclusion These results indicate that curcumin could increase the expression of SC-NSPCs, and reduce the activity of reactive astrogliosis and lesion cavity. Consequently curcumin could improve the functional recovery after SCI via SC-NSPC properties. PMID:29354231

Ebselen protects mitochondrial function and oxidative stress while inhibiting the mitochondrial apoptosis pathway after acute spinal cord injury.

PubMed

Jia, Zhi-Qiang; Li, San-Qiang; Qiao, Wei-Qiang; Xu, Wen-Zhong; Xing, Jian-Wu; Liu, Jian-Tao; Song, Hui; Gao, Zhong-Yang; Xing, Bing-Wen; He, Xi-Jing

2018-05-04

Ebselen is a fat-soluble small molecule and organic selenium compound that regulates the activity of glutathione peroxidase to alleviate mitochondrial oxidative stress and improve mitochondrial function. In the present study, we aimed to investigate the effects of ebselen on mitochondrial oxidative stress response, mitochondrial apotosis, and motor behaviors after spinal cord injury (SCI). We found that ebselen significantly increased the BBB score in motor behavior, thus suggesting a rescue effect of ebselen on motor function after SCI in rats. Meanwhile, we revealed that ebselen can increase glutathione (GSH) content as well as superoxide dismutase (SOD) and catalase (CAT) activities after SCI-this suggests ebselen has an antioxidant effect. Furthermore, the ATP content and Na + -K + -ATPase activity in mitochondria were increased by ebselen after SCI, while the mitochondrial membrane potential (MMP) was decreased by ebselen. The Cytochrome C and Smac release from mitochondria were reduced by ebselen after SCI, thus indicating improved membrane permeability by ebselen. Moreover, the alterations in caspase-3, Bax and Bcl-2 protein expression, as well as the proportion of cell apoptosis were improved by ebselen treatment, which together suggested that ebselen has an inhibitory effect on mitochondrial apotosis pathways after SCI. Taken together, our results suggest that ebselen can inhibit secondary damage caused by spinal cord injury. Indeed it plays a neuroprotective role in spinal cord injury perhaps by improving mitochondrial function and inhibiting the mitochondrial apoptosis pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Treatment of spinal fractures with paraplegia.

PubMed

Riska, E B; Myllynen, P

1981-01-01

Of 206 patients with vertebral fractures in the thoraco-lumbar spine with spinal cord injuries, an antero-lateral decompression with stabilization of the injured segment of the vertebral column was undertaken in 56 cases. In all these cases there was a compression of the spinal cord from the front. 8 patients made a complete recovery, 31 a good recovery, and 6 were improved. In 8 patients no improvement was noted. 2 patients developed pressure sores later and 1 patient died one year after the operation of uraemia. 22 patients out of 55 got a normal function of the bladder and 25 patients out of 54 a normal function of the anal sphincter. 16 patients out of 17 made a complete or good recovery after removal of a displaced rotated vertebral bony fragment from the spinal canal, and 7 patients out of 9 with wedge shaped fractures. In our clinic today, in cases of vertebral fractures with neural involvement, reduction and internal fixation with Harrington rods and fusion of the injured segment is undertaken as soon as possible, also during the night. If narrowing of the neural canal and compression of the spinal cord are verified, a decompression operation with interbody fusion is undertaken during the next days.

Transplanted Peripheral Blood Stem Cells Mobilized by Granulocyte Colony-Stimulating Factor Promoted Hindlimb Functional Recovery After Spinal Cord Injury in Mice.

PubMed

Takahashi, Hiroshi; Koda, Masao; Hashimoto, Masayuki; Furuya, Takeo; Sakuma, Tsuyoshi; Kato, Kei; Okawa, Akihiko; Inada, Taigo; Kamiya, Koshiro; Ota, Mitsutoshi; Maki, Satoshi; Takahashi, Kazuhisa; Yamazaki, Masashi; Mannoji, Chikato

2016-01-01

Granulocyte colony-stimulating factor (G-CSF) mobilizes peripheral blood stem cells (PBSCs) derived from bone marrow. We hypothesized that intraspinal transplantation of PBSCs mobilized by G-CSF could promote functional recovery after spinal cord injury. Spinal cords of adult nonobese diabetes/severe immunodeficiency mice were injured using an Infinite Horizon impactor (60 kdyn). One week after the injury, 3.0 µl of G-CSF-mobilized human mononuclear cells (MNCs; 0.5 × 10(5)/µl), G-CSF-mobilized human CD34-positive PBSCs (CD34; 0.5 × 10(5)/µl), or normal saline was injected to the lesion epicenter. We performed immunohistochemistry. Locomotor recovery was assessed by Basso Mouse Scale. The number of transplanted human cells decreased according to the time course. The CD31-positive area was significantly larger in the MNC and CD34 groups compared with the vehicle group. The number of serotonin-positive fibers was significantly larger in the MNC and CD34 groups than in the vehicle group. Immunohistochemistry revealed that the number of apoptotic oligodendrocytes was significantly smaller in cell-transplanted groups, and the areas of demyelination in the MNC- and CD34-transplanted mice were smaller than that in the vehicle group, indicating that cell transplantation suppressed oligodendrocyte apoptosis and demyelination. Both the MNC and CD34 groups showed significantly better hindlimb functional recovery compared with the vehicle group. There was no significant difference between the two types of transplanted cells. Intraspinal transplantation of G-CSF-mobilized MNCs or CD34-positive cells promoted angiogenesis, serotonergic fiber regeneration/sparing, and preservation of myelin, resulting in improved hindlimb function after spinal cord injury in comparison with vehicle-treated control mice. Transplantation of G-CSF-mobilized PBSCs has advantages for treatment of spinal cord injury in the ethical and immunological viewpoints, although further exploration is needed to move forward to clinical application.

Spinal cord regeneration in Xenopus tadpoles proceeds through activation of Sox2-positive cells

PubMed Central

2012-01-01

Background In contrast to mammals, amphibians, such as adult urodeles (for example, newts) and anuran larvae (for example, Xenopus) can regenerate their spinal cord after injury. However, the cellular and molecular mechanisms involved in this process are still poorly understood. Results Here, we report that tail amputation results in a global increase of Sox2 levels and proliferation of Sox2+ cells. Overexpression of a dominant negative form of Sox2 diminished proliferation of spinal cord resident cells affecting tail regeneration after amputation, suggesting that spinal cord regeneration is crucial for the whole process. After spinal cord transection, Sox2+ cells are found in the ablation gap forming aggregates. Furthermore, Sox2 levels correlated with regenerative capabilities during metamorphosis, observing a decrease in Sox2 levels at non-regenerative stages. Conclusions Sox2+ cells contribute to the regeneration of spinal cord after tail amputation and transection. Sox2 levels decreases during metamorphosis concomitantly with the lost of regenerative capabilities. Our results lead to a working hypothesis in which spinal cord damage activates proliferation and/or migration of Sox2+ cells, thus allowing regeneration of the spinal cord after tail amputation or reconstitution of the ependymal epithelium after spinal cord transection. PMID:22537391

Twiddler's syndrome in spinal cord stimulation.

PubMed

Al-Mahfoudh, Rafid; Chan, Yuen; Chong, Hsu Pheen; Farah, Jibril Osman

2016-01-01

The aims are to present a case series of Twiddler's syndrome in spinal cord stimulators with analysis of the possible mechanism of this syndrome and discuss how this phenomenon can be prevented. Data were collected retrospectively between 2007 and 2013 for all patients presenting with failure of spinal cord stimulators. The diagnostic criterion for Twiddler's syndrome is radiological evidence of twisting of wires in the presence of failure of spinal cord stimulation. Our unit implants on average 110 spinal cord stimulators a year. Over the 5-year study period, all consecutive cases of spinal cord stimulation failure were studied. Three patients with Twiddler's syndrome were identified. Presentation ranged from 4 to 228 weeks after implantation. Imaging revealed repeated rotations and twisting of the wires of the spinal cord stimulators leading to hardware failure. To the best of our knowledge this is the first reported series of Twiddler's syndrome with implantable pulse generators (IPGs) for spinal cord stimulation. Hardware failure is not uncommon in spinal cord stimulation. Awareness and identification of Twiddler's syndrome may help prevent its occurrence and further revisions. This may be achieved by implanting the IPG in the lumbar region subcutaneously above the belt line. Psychological intervention may have a preventative role for those who are deemed at high risk of Twiddler's syndrome from initial psychological screening.

Characteristics of spinal cord stroke in clinical neurology.

PubMed

Romi, Fredrik; Naess, Halvor

2011-01-01

Spinal cord stroke accounts for about 0.3% of all strokes in our department. Thirty-two patients (15 males, 17 females; mean age 63.3 years) treated in the period 1995-2010 were included. Patients underwent thorough investigation including the use of different stroke scales (National Institute of Health Stroke Scale, Barthel Index and modified Rankin Scale). Twenty-eight patients had infarctions, 3 had hemorrhages, and 1 had arterio-venous fistula. Twenty-eight spinal cord strokes were spontaneous, 2 were secondary to aorta aneurysms, and 2 post surgery. Biphasic ictus was seen in 17% of all spontaneous infarctions. Younger age, male gender, hypertension, diabetes mellitus, and higher blood glucose on admission regardless of diabetes mellitus, were risk factors associated with more severe spinal cord stroke. Treatment and prevention of these risk factors should be essential in spinal cord stroke. We recommend a clinical classification into upper (cervical) and lower (thoracic or medullary conus) spinal cord strokes. Patients with upper strokes in this study had more severe strokes initially, but they had a better prognosis. Therefore it is important to identify this patient group.Acute sensory spinal cord deficit symptoms, common initial symptoms in biphasic spinal cord strokes, should be considered as possible spinal cord stroke, especially when preceded by radiating pain between the shoulders. Copyright © 2011 S. Karger AG, Basel.

Electrical field distribution within the injured cat spinal cord: injury potentials and field distribution.

PubMed

Khan, T; Myklebust, J; Swiontek, T; Sayers, S; Dauzvardis, M

1994-12-01

This study investigated the spontaneous injury potentials measured after contusion or transection injury to the cat spinal cord. In addition, the distribution of electrical field potentials on the surface and within the spinal cord were measured following applied electrical fields after transection and contusion injuries. After transection of the spinal cord, the injury potentials were -19.8 +/- 2.6 mV; after contusion of the spinal cord, the injury potentials were -9.5 +/- 2.2 mV. These potentials returned to control values within 2.5-4h after injury. The electrical field distribution measured on the dorsal surface, as well as within the spinal cord, after the application of a 10 microA current, showed little difference between contusion and transection injuries. Scalar potential fields were measured using two configurations of stimulating electrodes: dorsal to dorsal (D-D), in which both electrodes were placed epidurally on the dorsal surface of the spinal cord, and ventral to dorsal (V-D), in which one electrode was placed dorsally and one ventrally. As reported in normal uninjured cats, the total current in the midsagittal plane for the D-D configuration was largely confined to the dorsal portion of the spinal cord; with the V-D configuration, the current distribution was uniform throughout the spinal cord. In the injured spinal cord, the equipotential lines midway between the stimulating electrodes have a wider separation than in the uninjured spinal cord. Because the magnitude of the electrical field E is equal to the current density J multiplied by the resistivity r, this suggests that either the current density is reduced or that the resistivity is reduced.

Gastrointestinal symptoms in spinal cord injury: relationships with level of injury and psychologic factors.

PubMed

Ng, Clinton; Prott, Gillian; Rutkowski, Susan; Li, Yueming; Hansen, Ross; Kellow, John; Malcolm, Allison

2005-08-01

Previous surveys of gastrointestinal symptoms after spinal cord injury have not used validated questionnaires and have not focused on the full spectrum of such symptoms and their relationship to factors, such as level of spinal cord injury and psychologic dysfunction. This study was designed to detail the spectrum and prevalence of gastrointestinal symptoms in spinal cord injury and to determine clinical and psychologic factors associated with such symptoms. Established spinal cord injury patients (>12 months) randomly selected from a spinal cord injury database completed the following three questionnaires: 1) Rome II Integrative Questionnaire, 2) Hospital Anxiety and Depression Scale, and 3) Burwood Bowel Dysfunction after spinal cord injury. A total of 110 patients participated. The prevalence of abdominal bloating and constipation were 22 and 46 percent, respectively. Bloating was associated with cervical (odds ratio = 9.5) and lumbar (odds ratio = 12.1) level but not with thoracic level of injury. Constipation was associated with a higher level of injury (cervical odds ratio = 5.6 vs. lumbar) but not with psychologic factors. In contrast, abdominal pain (33 percent) and fecal incontinence (41 percent) were associated with higher levels of anxiety (odds ratio = 6.8, and odds ratio = 2.4) but not with the level of injury. There is a high prevalence and wide spectrum of gastrointestinal symptoms in spinal cord injury. Abdominal bloating and constipation are primarily related to specific spinal cord levels of injury, whereas abdominal pain and fecal incontinence are primarily associated with higher levels of anxiety. Based on our findings, further physiologic and psychologic research studies in spinal cord injury patients should lead to more rational management strategies for the common gastrointestinal symptoms in spinal cord injury.

Topologically preserving straightening of spinal cord MRI.

PubMed

De Leener, Benjamin; Mangeat, Gabriel; Dupont, Sara; Martin, Allan R; Callot, Virginie; Stikov, Nikola; Fehlings, Michael G; Cohen-Adad, Julien

2017-10-01

To propose a robust and accurate method for straightening magnetic resonance (MR) images of the spinal cord, based on spinal cord segmentation, that preserves spinal cord topology and that works for any MRI contrast, in a context of spinal cord template-based analysis. The spinal cord curvature was computed using an iterative Non-Uniform Rational B-Spline (NURBS) approximation. Forward and inverse deformation fields for straightening were computed by solving analytically the straightening equations for each image voxel. Computational speed-up was accomplished by solving all voxel equation systems as one single system. Straightening accuracy (mean and maximum distance from straight line), computational time, and robustness to spinal cord length was evaluated using the proposed and the standard straightening method (label-based spline deformation) on 3T T 2 - and T 1 -weighted images from 57 healthy subjects and 33 patients with spinal cord compression due to degenerative cervical myelopathy (DCM). The proposed algorithm was more accurate, more robust, and faster than the standard method (mean distance = 0.80 vs. 0.83 mm, maximum distance = 1.49 vs. 1.78 mm, time = 71 vs. 174 sec for the healthy population and mean distance = 0.65 vs. 0.68 mm, maximum distance = 1.28 vs. 1.55 mm, time = 32 vs. 60 sec for the DCM population). A novel image straightening method that enables template-based analysis of quantitative spinal cord MRI data is introduced. This algorithm works for any MRI contrast and was validated on healthy and patient populations. The presented method is implemented in the Spinal Cord Toolbox, an open-source software for processing spinal cord MRI data. 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1209-1219. © 2017 International Society for Magnetic Resonance in Medicine.

Cytoarchitecture of the spinal cord of the postnatal (P4) mouse.

PubMed

Sengul, Gulgun; Puchalski, Ralph B; Watson, Charles

2012-05-01

Interpretation of the new wealth of gene expression and molecular mechanisms in the developing mouse spinal cord requires an accurate anatomical base on which data can be mapped. Therefore, we have assembled a spinal cord atlas of the P4 mouse to facilitate direct comparison with the adult specimens and to contribute to studies of the development of the mouse spinal cord. This study presents the anatomy of the spinal cord of the P4 C57Bl/6J mouse using Nissl and acetyl cholinesterase-stained sections. It includes a detailed map of the laminar organization of selected spinal cord segments and a description of named cell groups of the spinal cord such as the central cervical (CeCv), lateral spinal nucleus, lateral cervical, and dorsal nuclei. The motor neuron groups have also been identified according to the muscle groups they are likely to supply. General features of Rexed's laminae of the P4 spinal cord showed similarities to that of the adult (P56). However, certain differences were observed with regard to the extent of laminae and location of certain cell groups, such as the dorsal nucleus having a more dispersed structure and a more ventral and medial position or the CeCv being located in the medial part of lamina 5 in contrast to the adult where it is located in lamina 7. Motor neuron pools appeared to be more tightly packed in the P4 spinal cord. The dorsal horn was relatively larger and there was more white matter in the P56 spinal cord. Copyright © 2012 Wiley Periodicals, Inc.

General Information about Childhood Brain and Spinal Cord Tumors

MedlinePlus

... Cord Tumors Treatment Overview (PDQ®)–Patient Version General Information About Childhood Brain and Spinal Cord Tumors Go ... types of brain and spinal cord tumors. The information from tests and procedures done to detect (find) ...

The beneficial effects of treadmill step training on activity-dependent synaptic and cellular plasticity markers after complete spinal cord injury.

PubMed

Ilha, Jocemar; Centenaro, Lígia A; Broetto Cunha, Núbia; de Souza, Daniela F; Jaeger, Mariane; do Nascimento, Patrícia S; Kolling, Janaína; Ben, Juliana; Marcuzzo, Simone; Wyse, Angela T S; Gottfried, Carmem; Achaval, Matilde

2011-06-01

Several studies have shown that treadmill training improves neurological outcomes and promotes plasticity in lumbar spinal cord of spinal animals. The morphological and biochemical mechanisms underlying these phenomena remain unclear. The purpose of this study was to provide evidence of activity-dependent plasticity in spinal cord segment (L5) below a complete spinal cord transection (SCT) at T8-9 in rats in which the lower spinal cord segments have been fully separated from supraspinal control and that subsequently underwent treadmill step training. Five days after SCT, spinal animals started a step-training program on a treadmill with partial body weight support and manual step help. Hindlimb movements were evaluated over time and scored on the basis of the open-field BBB scale and were significantly improved at post-injury weeks 8 and 10 in trained spinal animals. Treadmill training also showed normalization of withdrawal reflex in trained spinal animals, which was significantly different from the untrained animals at post-injury weeks 8 and 10. Additionally, compared to controls, spinal rats had alpha motoneuronal soma size atrophy and reduced synaptophysin protein expression and Na(+), K(+)-ATPase activity in lumbar spinal cord. Step-trained rats had motoneuronal soma size, synaptophysin expression and Na(+), K(+)-ATPase activity similar to control animals. These findings suggest that treadmill step training can promote activity-dependent neural plasticity in lumbar spinal cord, which may lead to neurological improvements without supraspinal descending control after complete spinal cord injury.

Longitudinal Recovery and Reduced Costs After 120 Sessions of Locomotor Training for Motor Incomplete Spinal Cord Injury.

PubMed

Morrison, Sarah A; Lorenz, Douglas; Eskay, Carol P; Forrest, Gail F; Basso, D Michele

2018-03-01

To determine the impact of long-term, body weight-supported locomotor training after chronic, incomplete spinal cord injury (SCI), and to estimate the health care costs related to lost recovery potential and preventable secondary complications that may have occurred because of visit limits imposed by insurers. Prospective observational cohort with longitudinal follow-up. Eight outpatient rehabilitation centers that participate in the Christopher & Dana Reeve Foundation NeuroRecovery Network (NRN). Individuals with motor incomplete chronic SCI (American Spinal Injury Association Impairment Scale C or D; N=69; 0.1-45y after SCI) who completed at least 120 NRN physical therapy sessions. Manually assisted locomotor training (LT) in a body weight-supported treadmill environment, overground standing and stepping activities, and community integration tasks. International Standards for Neurological Classification of Spinal Cord Injury motor and sensory scores, orthostatic hypotension, bowel/bladder/sexual function, Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI), Berg Balance Scale, Modified Functional Reach, 10-m walk test, and 6-minute walk test. Longitudinal outcome measure collection occurred every 20 treatments and at 6- to 12-month follow-up after discharge from therapy. Significant improvement occurred for upper and lower motor strength, functional activities, psychological arousal, sensation of bowel movement, and SCI-FAI community ambulation. Extended training enabled minimal detectable changes at 60, 80, 100, and 120 sessions. After detectable change occurred, it was sustained through 120 sessions and continued 6 to 12 months after treatment. Delivering at least 120 sessions of LT improves recovery from incomplete chronic SCI. Because walking reduces rehospitalization, LT delivered beyond the average 20-session insurance limit can reduce rehospitalizations and long-term health costs. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Anatomical and functional evidence for trace amines as unique modulators of locomotor function in the mammalian spinal cord

PubMed Central

Gozal, Elizabeth A.; O'Neill, Brannan E.; Sawchuk, Michael A.; Zhu, Hong; Halder, Mallika; Chou, Ching-Chieh; Hochman, Shawn

2014-01-01

The trace amines (TAs), tryptamine, tyramine, and β-phenylethylamine, are synthesized from precursor amino acids via aromatic-L-amino acid decarboxylase (AADC). We explored their role in the neuromodulation of neonatal rat spinal cord motor circuits. We first showed that the spinal cord contains the substrates for TA biosynthesis (AADC) and for receptor-mediated actions via trace amine-associated receptors (TAARs) 1 and 4. We next examined the actions of the TAs on motor activity using the in vitro isolated neonatal rat spinal cord. Tyramine and tryptamine most consistently increased motor activity with prominent direct actions on motoneurons. In the presence of N-methyl-D-aspartate, all applied TAs supported expression of a locomotor-like activity (LLA) that was indistinguishable from that ordinarily observed with serotonin, suggesting that the TAs act on common central pattern generating neurons. The TAs also generated distinctive complex rhythms characterized by episodic bouts of LLA. TA actions on locomotor circuits did not require interaction with descending monoaminergic projections since evoked LLA was maintained following block of all Na+-dependent monoamine transporters or the vesicular monoamine transporter. Instead, TA (tryptamine and tyramine) actions depended on intracellular uptake via pentamidine-sensitive Na+-independent membrane transporters. Requirement for intracellular transport is consistent with the TAs having much slower LLA onset than serotonin and for activation of intracellular TAARs. To test for endogenous actions following biosynthesis, we increased intracellular amino acid levels with cycloheximide. LLA emerged and included distinctive TA-like episodic bouts. In summary, we provided anatomical and functional evidence of the TAs as an intrinsic spinal monoaminergic modulatory system capable of promoting recruitment of locomotor circuits independent of the descending monoamines. These actions support their known sympathomimetic function. PMID:25426030

Anatomical and functional evidence for trace amines as unique modulators of locomotor function in the mammalian spinal cord.

PubMed

Gozal, Elizabeth A; O'Neill, Brannan E; Sawchuk, Michael A; Zhu, Hong; Halder, Mallika; Chou, Ching-Chieh; Hochman, Shawn

2014-01-01

The trace amines (TAs), tryptamine, tyramine, and β-phenylethylamine, are synthesized from precursor amino acids via aromatic-L-amino acid decarboxylase (AADC). We explored their role in the neuromodulation of neonatal rat spinal cord motor circuits. We first showed that the spinal cord contains the substrates for TA biosynthesis (AADC) and for receptor-mediated actions via trace amine-associated receptors (TAARs) 1 and 4. We next examined the actions of the TAs on motor activity using the in vitro isolated neonatal rat spinal cord. Tyramine and tryptamine most consistently increased motor activity with prominent direct actions on motoneurons. In the presence of N-methyl-D-aspartate, all applied TAs supported expression of a locomotor-like activity (LLA) that was indistinguishable from that ordinarily observed with serotonin, suggesting that the TAs act on common central pattern generating neurons. The TAs also generated distinctive complex rhythms characterized by episodic bouts of LLA. TA actions on locomotor circuits did not require interaction with descending monoaminergic projections since evoked LLA was maintained following block of all Na(+)-dependent monoamine transporters or the vesicular monoamine transporter. Instead, TA (tryptamine and tyramine) actions depended on intracellular uptake via pentamidine-sensitive Na(+)-independent membrane transporters. Requirement for intracellular transport is consistent with the TAs having much slower LLA onset than serotonin and for activation of intracellular TAARs. To test for endogenous actions following biosynthesis, we increased intracellular amino acid levels with cycloheximide. LLA emerged and included distinctive TA-like episodic bouts. In summary, we provided anatomical and functional evidence of the TAs as an intrinsic spinal monoaminergic modulatory system capable of promoting recruitment of locomotor circuits independent of the descending monoamines. These actions support their known sympathomimetic function.

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.

Usability of a New Writing Assistive Device for Persons with Cervical Spinal Cord Injury.

PubMed

Lim, MyungJoon; Park, Jiyoung; Lee, Kuem Ju; Kweon, Hyosun; Kim, Byungchul; Cho, Kyujin; Choi, Hyun

2015-01-01

The hand function for persons with cervical spinal cord injury (PCSCI) is most frequently cause difficulties in leading normal lives. The purpose of this study was to test the usability of a new writing assistive device (NWAD) for PCSCI. To access its usability, the authors design usability testing method and test the NWAD to five individuals with cervical spinal cord injury. From the usability testing, we have found number of issues that lead us to key design concept about developing the NWAD. The NWAD will be redesigned based on the result of the present study. We expect that the NWAD will help PCSCI use their affected hand better and improve the level of independence and quality of life.

RAR/RXR and PPAR/RXR Signaling in Spinal Cord Injury

PubMed Central

van Neerven, Sabien; Mey, Jörg

2007-01-01

The retinoid acid receptors (RAR) and peroxisome proliferator-activated receptors (PPAR) have been implicated in the regulation of inflammatory reactions. Both receptor families contain ligand-activated transcription factors which form heterodimers with retinoid X receptors (RXR). We review data that imply RAR/RXR and PPAR/RXR pathways in physiological reactions after spinal cord injury. Experiments show how RAR signaling may improve axonal regeneration and modulate reactions of glia cells. While anti-inflammatory properties of PPAR are well documented in the periphery, their possible roles in the central nervous system have only recently become evident. Due to its anti-inflammatory function this transcription factor family promises to be a useful target after spinal cord or brain lesions. PMID:18060014

Pediatric intramedullary spinal cord lesions: Pathological spectrum and outcome of surgery

PubMed Central

Sahu, Rajni Kant; Das, Kuntal Kanti; Bhaisora, Kamlesh Singh; Singh, Amit Kumar; Mehrotra, Anant; Srivastava, Arun Kumar; Sahu, Rabi Narayan; Jaiswal, Awadhesh Kumar; Behari, Sanjay

2015-01-01

Background: Pediatric intramedullary spinal cord lesions are not only rare but also different from adults in a number of aspects. We aimed to study the incidence and the frequencies of various pediatric intramedullary mass lesions, their outcome to treatment and the factors determining their outcome of treatment. Materials and Methods: Thirty-one consecutive children (aged 1–18 years, mean 11.1 years, male: female = 1.8:1) with pathologically proven intramedullary spinal cord lesions treated at our center were studied. Clinico-radiological, histopathological, operative, and outcome data were reviewed retrospectively. The functional status was assessed using the modified McCormick grading system. Results: Gross total tumor excision was performed in 19 patients (61.3%), subtotal in 9 patients (29%), partial excision was performed in 2 (6.5%) patient, and only biopsy was performed in 1 patient (6.5%). There was one peroperative death, 2 patients died at follow-up. Complications included wound related complications (n = 4), transient deterioration in the motor power, and respiratory complication requiring a tracheostomy. Six patients showed recurrence at a mean follow-up of 16.4 months. Developmental tumors, high-grade ependymomas, and incompletely excised grade 2 ependymomas showed a tendency to recur. Conclusions: Children constituted nearly 1/5th (17.4%) of intramedullary spinal cord tumors. Astrocytomas and ependymomas taken together constituted the most common intramedullary spinal lesions in children; however, developmental tumors predominated in the first decade. Children usually presented in good functional grades preoperatively and maintained good grades after surgery. Functional outcome was dependent on the preoperative neurological status and histopathology of the lesions. PMID:26557160

Intensive exercise program after spinal cord injury ("Full-On"): study protocol for a randomized controlled trial.

PubMed

Galea, Mary P; Dunlop, Sarah A; Davis, Glen M; Nunn, Andrew; Geraghty, Timothy; Hsueh, Ya-seng Arthur; Churilov, Leonid

2013-09-11

Rehabilitation after spinal cord injury (SCI) has traditionally involved teaching compensatory strategies for identified impairments and deficits in order to improve functional independence. There is some evidence that regular and intensive activity-based therapies, directed at activation of the paralyzed extremities, promotes neurological improvement. The aim of this study is to compare the effects of a 12-week intensive activity-based therapy program for the whole body with a program of upper body exercise. A multicenter, parallel group, assessor-blinded randomized controlled trial will be conducted. One hundred eighty-eight participants with spinal cord injury, who have completed their primary rehabilitation at least 6 months prior, will be recruited from five SCI units in Australia and New Zealand. Participants will be randomized to an experimental or control group. Experimental participants will receive a 12-week program of intensive exercise for the whole body, including locomotor training, trunk exercises and functional electrical stimulation-assisted cycling. Control participants will receive a 12-week intensive upper body exercise program. The primary outcome is the American Spinal Injuries Association (ASIA) Motor Score. Secondary outcomes include measurements of sensation, function, pain, psychological measures, quality of life and cost effectiveness. All outcomes will be measured at baseline, 12 weeks, 6 months and 12 months by blinded assessors. Recruitment commenced in January 2011. The results of this trial will determine the effectiveness of a 12-week program of intensive exercise for the whole body in improving neurological recovery after spinal cord injury. NCT01236976 (10 November 2010), ACTRN12610000498099 (17 June 2010).

What Are the Key Statistics about Brain and Spinal Cord Cancers?

MedlinePlus

... Brain and Spinal Cord Tumors in Adults Key Statistics for Brain and Spinal Cord Tumors The American ... Cord Tumors . Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Written by References ...

A Prediction Model for Functional Outcomes in Spinal Cord Disorder Patients Using Gaussian Process Regression.

PubMed

Lee, Sunghoon Ivan; Mortazavi, Bobak; Hoffman, Haydn A; Lu, Derek S; Li, Charles; Paak, Brian H; Garst, Jordan H; Razaghy, Mehrdad; Espinal, Marie; Park, Eunjeong; Lu, Daniel C; Sarrafzadeh, Majid

2016-01-01

Predicting the functional outcomes of spinal cord disorder patients after medical treatments, such as a surgical operation, has always been of great interest. Accurate posttreatment prediction is especially beneficial for clinicians, patients, care givers, and therapists. This paper introduces a prediction method for postoperative functional outcomes by a novel use of Gaussian process regression. The proposed method specifically considers the restricted value range of the target variables by modeling the Gaussian process based on a truncated Normal distribution, which significantly improves the prediction results. The prediction has been made in assistance with target tracking examinations using a highly portable and inexpensive handgrip device, which greatly contributes to the prediction performance. The proposed method has been validated through a dataset collected from a clinical cohort pilot involving 15 patients with cervical spinal cord disorder. The results show that the proposed method can accurately predict postoperative functional outcomes, Oswestry disability index and target tracking scores, based on the patient's preoperative information with a mean absolute error of 0.079 and 0.014 (out of 1.0), respectively.

Involvement of the Spinal Cord in Mitochondrial Disorders.

PubMed

Finsterer, Josef; Zarrouk-Mahjoub, Sinda

2018-01-01

This review aims at summarising and discussing the current status concerning the clinical presentation, pathogenesis, diagnosis, and treatment of spinal cord affection in mitochondrial disorders (MIDs). A literature search using the database Pubmed was carried out by application of appropriate search terms and their combinations. Involvement of the spinal cord in MIDs is more frequent than anticipated. It occurs in specific and non-specific MIDs. Among the specific MIDs it has been most frequently described in LBSL, LS, MERRF, KSS, IOSCA, MIRAS, and PCH and only rarely in MELAS, CPEO, and LHON. Clinically, spinal cord involvement manifests as monoparesis, paraparesis, quadruparesis, sensory disturbances, hypotonia, spasticity, urinary or defecation dysfunction, spinal column deformities, or as transverse syndrome. Diagnosing spinal cord involvement in MIDs requires a thoroughly taken history, clinical exam, and imaging studies. Additionally, transcranial magnetic stimulation, somato-sensory-evoked potentials, and cerebro-spinal fluid can be supportive. Treatment is generally not at variance compared to the underlying MID but occasionally surgical stabilisation of the spinal column may be necessary. It is concluded that spinal cord involvement in MIDs is more frequent than anticipated but may be missed if cerebral manifestations prevail. Spinal cord involvement in MIDs may strongly determine the mobility of these patients.

Human spinal locomotor control is based on flexibly organized burst generators.

PubMed

Danner, Simon M; Hofstoetter, Ursula S; Freundl, Brigitta; Binder, Heinrich; Mayr, Winfried; Rattay, Frank; Minassian, Karen

2015-03-01

Constant drive provided to the human lumbar spinal cord by epidural electrical stimulation can cause local neural circuits to generate rhythmic motor outputs to lower limb muscles in people paralysed by spinal cord injury. Epidural spinal cord stimulation thus allows the study of spinal rhythm and pattern generating circuits without their configuration by volitional motor tasks or task-specific peripheral feedback. To reveal spinal locomotor control principles, we studied the repertoire of rhythmic patterns that can be generated by the functionally isolated human lumbar spinal cord, detected as electromyographic activity from the legs, and investigated basic temporal components shared across these patterns. Ten subjects with chronic, motor-complete spinal cord injury were studied. Surface electromyographic responses to lumbar spinal cord stimulation were collected from quadriceps, hamstrings, tibialis anterior, and triceps surae in the supine position. From these data, 10-s segments of rhythmic activity present in the four muscle groups of one limb were extracted. Such samples were found in seven subjects. Physiologically adequate cycle durations and relative extension- and flexion-phase durations similar to those needed for locomotion were generated. The multi-muscle activation patterns exhibited a variety of coactivation, mixed-synergy and locomotor-like configurations. Statistical decomposition of the electromyographic data across subjects, muscles and samples of rhythmic patterns identified three common temporal components, i.e. basic or shared activation patterns. Two of these basic patterns controlled muscles to contract either synchronously or alternatingly during extension- and flexion-like phases. The third basic pattern contributed to the observed muscle activities independently from these extensor- and flexor-related basic patterns. Each bifunctional muscle group was able to express both extensor- and flexor-patterns, with variable ratios across the samples of rhythmic patterns. The basic activation patterns can be interpreted as central drives implemented by spinal burst generators that impose specific spatiotemporally organized activation on the lumbosacral motor neuron pools. Our data thus imply that the human lumbar spinal cord circuits can form burst-generating elements that flexibly combine to obtain a wide range of locomotor outputs from a constant, repetitive input. It may be possible to use this flexibility to incorporate specific adaptations to gait and stance to improve locomotor control, even after severe central nervous system damage. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Human spinal locomotor control is based on flexibly organized burst generators

PubMed Central

Danner, Simon M.; Hofstoetter, Ursula S.; Freundl, Brigitta; Binder, Heinrich; Mayr, Winfried; Rattay, Frank

2015-01-01

Constant drive provided to the human lumbar spinal cord by epidural electrical stimulation can cause local neural circuits to generate rhythmic motor outputs to lower limb muscles in people paralysed by spinal cord injury. Epidural spinal cord stimulation thus allows the study of spinal rhythm and pattern generating circuits without their configuration by volitional motor tasks or task-specific peripheral feedback. To reveal spinal locomotor control principles, we studied the repertoire of rhythmic patterns that can be generated by the functionally isolated human lumbar spinal cord, detected as electromyographic activity from the legs, and investigated basic temporal components shared across these patterns. Ten subjects with chronic, motor-complete spinal cord injury were studied. Surface electromyographic responses to lumbar spinal cord stimulation were collected from quadriceps, hamstrings, tibialis anterior, and triceps surae in the supine position. From these data, 10-s segments of rhythmic activity present in the four muscle groups of one limb were extracted. Such samples were found in seven subjects. Physiologically adequate cycle durations and relative extension- and flexion-phase durations similar to those needed for locomotion were generated. The multi-muscle activation patterns exhibited a variety of coactivation, mixed-synergy and locomotor-like configurations. Statistical decomposition of the electromyographic data across subjects, muscles and samples of rhythmic patterns identified three common temporal components, i.e. basic or shared activation patterns. Two of these basic patterns controlled muscles to contract either synchronously or alternatingly during extension- and flexion-like phases. The third basic pattern contributed to the observed muscle activities independently from these extensor- and flexor-related basic patterns. Each bifunctional muscle group was able to express both extensor- and flexor-patterns, with variable ratios across the samples of rhythmic patterns. The basic activation patterns can be interpreted as central drives implemented by spinal burst generators that impose specific spatiotemporally organized activation on the lumbosacral motor neuron pools. Our data thus imply that the human lumbar spinal cord circuits can form burst-generating elements that flexibly combine to obtain a wide range of locomotor outputs from a constant, repetitive input. It may be possible to use this flexibility to incorporate specific adaptations to gait and stance to improve locomotor control, even after severe central nervous system damage. PMID:25582580

Nuclear Organization in the Spinal Cord Depends on Motor Neuron Lamination Orchestrated by Catenin and Afadin Function.

PubMed

Dewitz, Carola; Pimpinella, Sofia; Hackel, Patrick; Akalin, Altuna; Jessell, Thomas M; Zampieri, Niccolò

2018-02-13

Motor neurons in the spinal cord are found grouped in nuclear structures termed pools, whose position is precisely orchestrated during development. Despite the emerging role of pool organization in the assembly of spinal circuits, little is known about the morphogenetic programs underlying the patterning of motor neuron subtypes. We applied three-dimensional analysis of motor neuron position to reveal the roles and contributions of cell adhesive function by inactivating N-cadherin, catenin, and afadin signaling. Our findings reveal that nuclear organization of motor neurons is dependent on inside-out positioning, orchestrated by N-cadherin, catenin, and afadin activities, controlling cell body layering on the medio-lateral axis. In addition to this lamination-like program, motor neurons undergo a secondary, independent phase of organization. This process results in segregation of motor neurons along the dorso-ventral axis of the spinal cord, does not require N-cadherin or afadin activity, and can proceed even when medio-lateral positioning is perturbed. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Methylprednisolone Administration Following Spinal Cord Injury Reduces Aquaporin 4 Expression and Exacerbates Edema

PubMed Central

Martínez-Cruz, Angelina; Reyes-Sánchez, Alejandro; Guizar-Sahagún, Gabriel

2017-01-01

Spinal cord injury (SCI) is an incapacitating condition that affects motor, sensory, and autonomic functions. Since 1990, the only treatment administered in the acute phase of SCI has been methylprednisolone (MP), a synthetic corticosteroid that has anti-inflammatory effects; however, its efficacy remains controversial. Although MP has been thought to help in the resolution of edema, there are no scientific grounds to support this assertion. Aquaporin 4 (AQP4), the most abundant component of water channels in the CNS, participates in the formation and elimination of edema, but it is not clear whether the modulation of AQP4 expression by MP plays any role in the physiopathology of SCI. We studied the functional expression of AQP4 modulated by MP following SCI in an experimental model in rats along with the associated changes in the permeability of the blood-spinal cord barrier. We analyzed these effects in male and female rats and found that SCI increased AQP4 expression in the spinal cord white matter and that MP diminished such increase to baseline levels. Moreover, MP increased the extravasation of plasma components after SCI and enhanced tissue swelling and edema. Our results lend scientific support to the increasing motion to avoid MP treatment after SCI. PMID:28572712

Usability assessment of ASIBOT: a portable robot to aid patients with spinal cord injury.

PubMed

Jardón, Alberto; Gil, Ángel M; de la Peña, Ana I; Monje, Concepción A; Balaguer, Carlos

2011-01-01

The usability concept refers to aspects related to the use of products that are closely linked to the user's degree of satisfaction. Our goal is to present a functional evaluation methodology for assessing the usability of sophisticated technical aids, such as a portable robot for helping disabled patients with severe spinal cord injuries. The specific manipulator used for this task is ASIBOT, a personal assistance robot totally developed by RoboticsLab at the University Carlos III of Madrid. Our purpose is also to improve some aspects of the manipulator according to the user's perception. For our case study, a population of six patients with spinal cord injury is considered. These patients have been suffering spinal cord injuries for a period of time longer than 1 year before the tests are carried out. The methodology followed for the information gathering is based on the Quebec User Evaluation of Satisfaction with assistive Technology (QUEST). Different daily functions, such as drinking, brushing one's teeth and washing one's face, are considered to assess the user's perception when using ASIBOT as a technical aid. The human factor in this procedure is the main base to establish the specific needs and tools to make the end product more suitable and usable.

International bowel function basic spinal cord injury data set.

PubMed

Krogh, K; Perkash, I; Stiens, S A; Biering-Sørensen, F

2009-03-01

International expert working group. To develop an International Bowel Function Basic Spinal Cord Injury (SCI) Data Set presenting a standardized format for the collection and reporting of a minimal amount of information on bowel function in daily practice or in research. Working group consisting of members appointed by the American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS). A draft prepared by the working group was reviewed by Executive Committee of the International SCI Standards and Data Sets, and later by ISCoS Scientific Committee and the ASIA Board. Relevant and interested scientific and professional (international) organizations and societies (approximately 40) were also invited to review the data set and it was posted on the ISCoS and ASIA websites for 3 months to allow comments and suggestions. The ISCoS Scientific Committee, Council and ASIA Board received the data set for final review and approval. The International Bowel Function Basic SCI Data Set includes the following 12 items: date of data collection, gastrointestinal or anal sphincter dysfunction unrelated to SCI, surgical procedures on the gastrointestinal tract, awareness of the need to defecate, defecation method and bowel care procedures, average time required for defecation, frequency of defecation, frequency of fecal incontinence, need to wear pad or plug, medication affecting bowel function/constipating agents, oral laxatives and perianal problems. An International Bowel Function Basic SCI Data Set has been developed.

Oral erlotinib, but not rapamycin, causes modest acceleration of bladder and hindlimb recovery from spinal cord injury in rats.

PubMed

Kjell, J; Pernold, K; Olson, L; Abrams, M B

2014-03-01

Erlotinib and Rapamycin are both in clinical use and experimental inhibition of their respective molecular targets, EGFR and mTORC1, has improved recovery from spinal cord injury. Our aim was to determine if daily Erlotinib or Rapamycin treatment started directly after spinal contusion injury in rats improves locomotion function or recovery of bladder function. Stockholm, Sweden. Rats were subjected to contusion injuries and treated during the acute phase with either Erlotinib or Rapamycin. Recovery of bladder function was monitored by measuring residual urine volume and hindlimb locomotion assessed by open-field observations using the BBB rating scale as well as by automated registration of gait parameters. Body weights were monitored. To determine whether Erlotinib and Rapamycin inhibit the same signaling pathway, a cell culture system and western blots were used. Erlotinib accelerated locomotor recovery and slightly improved bladder recovery; however, we found no long-term improvements of locomotor function. Rapamycin did neither improved locomotor function nor bladder recovery. In vitro studies confirmed that Erlotinib and Rapamycin both inhibit the EGFR-mTORC1 signaling pathway. We conclude that none of these two drug regimes improved long-term functional outcome in our current model of spinal cord injury. Nevertheless, oral treatment with Erlotinib may offer modest temporary advantages, whereas treatment with Rapamycin does not.

Panax ginseng Improves Functional Recovery after Contusive Spinal Cord Injury by Regulating the Inflammatory Response in Rats: An In Vivo Study

PubMed Central

Kim, Young Ock; Kim, Youngkyung; Lee, Koeun; Na, Sae Won; Hong, Seon Pyo; Valan Arasu, Mariadhas; Yoon, Young Wook; Kim, Junesun

2015-01-01

Spinal cord injury (SCI) results in permanent loss of motor function below the injured site. Neuroinflammatory reaction following SCI can aggravate neural injury and functional impairment. Ginseng is well known to possess anti-inflammatory effects. The present study investigated the neuroprotective effects of Panax ginseng C.A. Mayer (P. ginseng) after SCI. A spinal contusion was made at the T11-12 spinal cord in adult male Sprague-Dawley rats (n = 47) using the NYU impactor. Motor function was assessed using the Basso-Beattie-Bresnahan (BBB) score in P. ginseng (0.1, 0.5, 1, 3, and 5 mg/kg) or vehicle (saline) treated after SCI. We also assessed the protein expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) at the lesion site by western blot and then measured the cavity area using luxol fast blue/cresyl violet staining. P. ginseng treated group in SCI showed a significant improvement in locomotor function after the injury. The protein expression of COX-2 and iNOS at the lesion site and the cavity area were decreased following SCI by P. ginseng treatment. These results suggest that P. ginseng may improve the recovery of motor function after SCI which provides neuroprotection by alleviating posttraumatic inflammatory responses. PMID:26451158

The Extract of Roots of Sophora flavescens Enhances the Recovery of Motor Function by Axonal Growth in Mice with a Spinal Cord Injury

PubMed Central

Tanabe, Norio; Kuboyama, Tomoharu; Kazuma, Kohei; Konno, Katsuhiro; Tohda, Chihiro

2016-01-01

Although axonal extension to reconstruct spinal tracts should be effective for restoring function after spinal cord injury (SCI), chondroitin sulfate proteoglycan (CSPG) levels increase at spinal cord lesion sites, and inhibit axonal regrowth. In this study, we found that the water extract of roots of Sophora flavescens extended the axons of mouse cortical neurons, even on a CSPG-coated surface. Consecutive oral administrations of S. flavescens extract to SCI mice for 31 days increased the density of 5-HT-positive axons at the lesion site and improved the motor function. Further, the active constituents in the S. flavescens extract were identified. The water and alkaloid fractions of the S. flavescens extract each exhibited axonal extension activity in vitro. LC/MS analysis revealed that these fractions mainly contain matrine and/or oxymatrine, which are well-known major compounds in S. flavescens. Matrine and oxymatrine promoted axonal extension on the CSPG-coated surface. This study is the first to demonstrate that S. flavescens extract, matrine, and oxymatrine enhance axonal growth in vitro, even on a CSPG-coated surface, and that S. flavescens extract improves motor function and increases axonal density in SCI mice. PMID:26834638

Protection of rats spinal cord ischemia-reperfusion injury by inhibition of MiR-497 on inflammation and apoptosis: Possible role in pediatrics.

PubMed

Xu, Meng; Wang, Hai-Feng; Zhang, Ying-Ying; Zhuang, Hui-Wen

2016-07-01

MicroRNAs are extensively included in the pathogenesis and progression of many diseases by inhibiting target gene expression. Recently, studies have demonstrated that microRNA-497 (miR-497) may be implicated in human breast cancer that miR-497 predicts the prognosis of breast cancer patients from the posttranscriptional level. However, the specific function of miR-497 in spinal cord ischemia-reperfusion (IR) injury is far from clear nowadays. The present study was designed to determine the role of miR-497 in spinal cord IR injury and investigate the underlying spinal cord protective mechanism. The rat spinal cord IR injury model was performed by occluding the left anterior descending coronary artery for 30 min, which is then followed by 12h reperfusion. As predicted, miR-497 over-expression markedly decreased the expression of IL-1 receptor associated kinase (IRAK1) and Cyclic AMP response element binding protein (CREB). Moreover, Toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB) and Caspase-3, as miR-497 potential targets were significantly suppressed after miR-497 transfection, then preventing inflammatory cytokines and factors regulating apoptosis. We also found that tumor necrosis factor-a (TNF-α) and interleukin-1beta (IL-1β) activity, pro-apoptotic related genes, such as extracellular regulated protein kinases (ERK), Bcl-2 Associated X Protein (Bax), Bcl-2, Bcl-xL levels were all decreased associated with the down-regulation of IRAK1 and CREB. In conclusion, our data demonstrate that miR-497 could inhibit inflammation and apoptosis of spinal cord IR through its targets, IRAK1 of TLR4 and CREB signaling pathway. Thus, miR-497 may constitute a new therapeutic target for the prevention of spinal cord IR injury. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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.

Degenerative Cervical Myelopathy: A Spectrum of Related Disorders Affecting the Aging Spine.

PubMed

Tetreault, Lindsay; Goldstein, Christina L; Arnold, Paul; Harrop, James; Hilibrand, Alan; Nouri, Aria; Fehlings, Michael G

2015-10-01

Cervical spinal cord dysfunction can result from either traumatic or nontraumatic causes, including tumors, infections, and degenerative changes. In this article, we review the range of degenerative spinal disorders resulting in progressive cervical spinal cord compression and propose the adoption of a new term, degenerative cervical myelopathy (DCM). DCM comprises both osteoarthritic changes to the spine, including spondylosis, disk herniation, and facet arthropathy (collectively referred to as cervical spondylotic myelopathy), and ligamentous aberrations such as ossification of the posterior longitudinal ligament and hypertrophy of the ligamentum flavum. This review summarizes current knowledge of the pathophysiology of DCM and describes the cascade of events that occur after compression of the spinal cord, including ischemia, destruction of the blood-spinal cord barrier, demyelination, and neuronal apoptosis. Important features of the diagnosis of DCM are discussed in detail, and relevant clinical and imaging findings are highlighted. Furthermore, this review outlines valuable assessment tools for evaluating functional status and quality of life in these patients and summarizes the advantages and disadvantages of each. Other topics of this review include epidemiology, the prevalence of degenerative changes in the asymptomatic population, the natural history and rates of progression, risk factors of diagnosis (clinical, imaging and genetic), and management strategies.

Effect of Robotic-Assisted Gait Training in Patients With Incomplete Spinal Cord Injury

PubMed Central

Shin, Ji Cheol; Kim, Ji Yong; Park, Han Kyul

2014-01-01

Objective To determine the effect of robotic-assisted gait training (RAGT) compared to conventional overground training. Methods Sixty patients with motor incomplete spinal cord injury (SCI) were included in a prospective, randomized clinical trial by comparing RAGT to conventional overground training. The RAGT group received RAGT three sessions per week at duration of 40 minutes with regular physiotherapy in 4 weeks. The conventional group underwent regular physiotherapy twice a day, 5 times a week. Main outcomes were lower extremity motor score of American Spinal Injury Association impairment scale (LEMS), ambulatory motor index (AMI), Spinal Cord Independence Measure III mobility section (SCIM3-M), and walking index for spinal cord injury version II (WISCI-II) scale. Results At the end of rehabilitation, both groups showed significant improvement in LEMS, AMI, SCIM3-M, and WISCI-II. Based on WISCI-II, statistically significant improvement was observed in the RAGT group. For the remaining variables, no difference was found. Conclusion RAGT combined with conventional physiotherapy could yield more improvement in ambulatory function than conventional therapy alone. RAGT should be considered as one additional tool to provide neuromuscular reeducation in patient with incomplete SCI. PMID:25566469

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.

Lentiviral-mediated Targeted NF-κB Blockade in Dorsal Spinal Cord Glia Attenuates Sciatic Nerve Injury-induced Neuropathic Pain in the Rat.

PubMed

Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

2007-04-01

Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor κB (NF-κB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-κB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-κB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-κB super- repressor IκBα resulted in an inhibition of the NF-κB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IκBα overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-κB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-κB pathway in the development of neuropathic pain after peripheral nerve injury. Copyright © 2007 The American Society of Gene Therapy. Published by Elsevier Inc. All rights reserved.

Imaging spinal cord atrophy in progressive myelopathies: HTLV-I-associated neurological disease (HAM/TSP) and multiple sclerosis (MS).

PubMed

Azodi, Shila; Nair, Govind; Enose-Akahata, Yoshimi; Charlip, Emily; Vellucci, Ashley; Cortese, Irene; Dwyer, Jenifer; Billioux, B Jeanne; Thomas, Chevaz; Ohayon, Joan; Reich, Daniel S; Jacobson, Steven

2017-11-01

Previous work measures spinal cord thinning in chronic progressive myelopathies, including human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and multiple sclerosis (MS). Quantitative measurements of spinal cord atrophy are important in fully characterizing these and other spinal cord diseases. We aimed to investigate patterns of spinal cord atrophy and correlations with clinical markers. Spinal cord cross-sectional area was measured in individuals (24 healthy controls [HCs], 17 asymptomatic carriers of HTLV-1 (AC), 47 HAM/TSP, 74 relapsing-remitting MS [RRMS], 17 secondary progressive MS [SPMS], and 40 primary progressive MS [PPMS]) from C1 to T10. Clinical disability scores, viral markers, and immunological parameters were obtained for patients and correlated with representative spinal cord cross-sectional area regions at the C2 to C3, C4 to C5, and T4 to T9 levels. In 2 HAM/TSP patients, spinal cord cross-sectional area was measured over 3 years. All spinal cord regions are thinner in HAM/TSP (56 mm 2 [standard deviation, 10], 59 [10], 23 [5]) than in HC (76 [7], 83 [8], 38 [4]) and AC (71 [7], 78 [9], 36 [7]). SPMS (62 [9], 66 [9], 32 [6]) and PPMS (65 [11], 68 [10], 35 [7]) have thinner cervical cords than HC and RRMS (73 [9], 77 [10], 37 [6]). Clinical disability scores (Expanded Disability Status Scale [p = 0.009] and Instituto de Pesquisas de Cananeia [p = 0.03]) and CD8 + T-cell frequency (p = 0.04) correlate with T4 to T9 spinal cord cross-sectional area in HAM/TSP. Higher cerebrospinal fluid HTLV-1 proviral load (p = 0.01) was associated with thinner spinal cord cross-sectional area. Both HAM/TSP patients followed longitudinally showed thoracic thinning followed by cervical thinning. Group average spinal cord cross-sectional area in HAM/TSP and progressive MS show spinal cord atrophy. We further hypothesize in HAM/TSP that is possible that neuroglial loss from a thoracic inflammatory process results in anterograde and retrograde degeneration of axons, leading to the temporal progression of thoracic to cervical atrophy described here. Ann Neurol 2017;82:719-728. © 2017 American Neurological Association.

Migration of luque rods through a laminectomy defect causing spinal cord compression.

PubMed

Quint, D J; Salton, G

1993-01-01

Internal fixation of traumatic spinal injuries has been associated with spinal canal stenosis, spinal cord compression, and nerve root impingement. We present a case of spinal cord/cauda equina compression due to migration of intact, anchored thoracolumbar Luque rods into the spinal canal through a laminectomy defect, leading to neurologic complications 10 years after the original operation.

Studies on the cellular localization of spinal cord substance P receptors.

PubMed

Helke, C J; Charlton, C G; Wiley, R G

1986-10-01

Substance P-immunoreactivity and specific substance P binding sites are present in the spinal cord. Receptor autoradiography showed the discrete localization of substance P binding sites in both sensory and motor regions of the spinal cord and functional studies suggested an important role for substance P receptor activation in autonomic outflow, nociception, respiration and somatic motor function. In the current studies, we investigated the cellular localization of substance P binding sites in rat spinal cord using light microscopic autoradiography combined with several lesioning techniques. Unilateral injections of the suicide transport agent, ricin, into the superior cervical ganglion reduced substance P binding and cholinesterase-stained preganglionic sympathetic neurons in the intermediolateral cell column. However, unilateral electrolytic lesions of ventral medullary substance P neurons which project to the intermediolateral cell column did not alter the density of substance P binding in the intermediolateral cell column. Likewise, 6-hydroxydopamine and 5,7-dihydroxytryptamine, which destroy noradrenergic and serotonergic nerve terminals, did not reduce the substance P binding in the intermediolateral cell column. It appears, therefore, that the substance P binding sites are located postsynaptically on preganglionic sympathetic neurons rather than presynaptically on substance P-immunoreactive processes (i.e. as autoreceptors) or on monoamine nerve terminals. Unilateral injections of ricin into the phrenic nerve resulted in the unilateral destruction of phrenic motor neurons in the cervical spinal cord and caused a marked reduction in the substance P binding in the nucleus. Likewise, sciatic nerve injections of ricin caused a loss of associated motor neurons in the lateral portion of the ventral horn of the lumbar spinal cord and a reduction in the substance P binding. Sciatic nerve injections of ricin also destroyed afferent nerves of the associated dorsal root ganglia and increased the density of substance P binding in the dorsal horn. Capsaicin, which destroys small diameter primary sensory neurons, similarly increased the substance P binding in the dorsal horn. These studies show that the cellular localization of substance P binding sites can be determined by analysis of changes in substance P binding to discrete regions of spinal cord after selective lesions of specific groups of neurons. The data show the presence of substance P binding sites on preganglionic sympathetic neurons in the intermediolateral cell column and on somatic motor neurons in the ventral horn, including the phrenic motor nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

Developmental regulation of N-methyl-D-aspartate- and kainate-type glutamate receptor expression in the rat spinal cord

NASA Technical Reports Server (NTRS)

Stegenga, S. L.; Kalb, R. G.

2001-01-01

Spinal motor neurons undergo experience-dependent development during a critical period in early postnatal life. It has been suggested that the repertoire of glutamate receptor subunits differs between young and mature motor neurons and contributes to this activity-dependent development. In the present study we examined the expression patterns of N-methyl-D-aspartate- and kainate-type glutamate receptor subunits during the postnatal maturation of the spinal cord. Young motor neurons express much higher levels of the N-methyl-D-aspartate receptor subunit NR1 than do adult motor neurons. Although there are eight potential splice variants of NR1, only a subgroup is expressed by motor neurons. With respect to NR2 receptor subunits, young motor neurons express NR2A and C, while adult motor neurons express only NR2A. Young motor neurons express kainate receptor subunits GluR5, 6 and KA2 but we are unable to detect these or any other kainate receptor subunits in the adult spinal cord. Other spinal cord regions display a distinct pattern of developmental regulation of N-methyl-D-aspartate and kainate receptor subunit expression in comparison to motor neurons. Our findings indicate a precise spatio-temporal regulation of individual subunit expression in the developing spinal cord. Specific combinations of subunits in developing neurons influence their excitable properties and could participate in the emergence of adult neuronal form and function.

Long-Term Extensive Ectopic Hair Growth on the Spinal Cord of Mice from Transplanted Whisker Follicles.

PubMed

Cao, Wenluo; Li, Lingna; Mii, Sumiyuki; Amoh, Yasuyuki; Liu, Fang; Hoffman, Robert M

2015-01-01

We have previously demonstrated that hair follicles contain nestin-expressing pluripotent stem cells that can effect nerve and spinal cord repair upon transplantation. In the present study, isolated whisker follicles from nestin-driven green fluorescent protein (ND-GFP) mice were histocultured on Gelfoam for 3 weeks for the purpose of transplantation to the spinal cord to heal an induced injury. The hair shaft was cut off from Gelfoam-histocultured whisker follicles, and the remaining part of the whisker follicles containing GFP-nestin expressing pluripotent stem cells were transplanted into the injured spinal cord of nude mice, along with the Gelfoam. After 90 days, the mice were sacrificed and the spinal cord lesion was observed to have healed. ND-GFP expression was intense at the healed area of the spinal cord, as observed by fluorescence microscopy, demonstrating that the hair follicle stem cells were involved in healing the spinal cord. Unexpectedly, the transplanted whisker follicles sprouted out remarkably long hair shafts in the spinal cord during the 90 days after transplantation of Gelfoam whisker histocultures to the injured spine. The pigmented hair fibers, grown from the transplanted whisker histocultures, curved and enclosed the spinal cord. The unanticipated results demonstrate the great potential of hair growth after transplantation of Gelfoam hair follicle histocultures, even at an ectopic site.

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.

Spinal cord stimulation for refractory angina in a patient implanted with a cardioverter defibrillator.

PubMed

Ferrero, Paolo; Grimaldi, Roberto; Massa, Riccardo; Chiribiri, Amedeo; De Luca, Anna; Castellano, Maddalena; Cardano, Paola; Trevi, Gian Paolo

2007-01-01

Spinal cord stimulation is currently used to treat refractory angina. Some concerns may arise about the possible interaction concerning the spinal cord stimulator in patients already implanted with a pacemaker or a cardioverter defibrillator. We are going to describe the successful implantation of a spinal cord stimulator in a patient previously implanted with a cardioverter defibrillator.

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.

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.

Exploration of Spinal Cord Aging–Related Proteins Using a Proteomics Approach

PubMed Central

Kamiya, Koshiro; Furuya, Takeo; Hashimoto, Masayuki; Mannoji, Chikato; Inada, Taigo; Ota, Mitsutoshi; Maki, Satoshi; Ijima, Yasushi; Saito, Junya; Kitamura, Mitsuhiro; Ohtori, Seiji; Orita, Sumihisa; Inage, Kazuhide; Yamazaki, Masashi; Koda, Masao

2017-01-01

How aging affects the spinal cord at a molecular level is unclear. The aim of this study was to explore spinal cord aging–related proteins that may be involved in pathological mechanisms of age-related changes in the spinal cord. Spinal cords of 2-year-old and 8-week-old female Sprague-Dawley rats were dissected from the animals. Protein samples were subjected to 2-dimentional polyacrylamide gel electrophoresis followed by mass spectrometry. Screened proteins were further investigated with immunohistochemistry and Western blotting. Among the screened proteins, we selected α-crystallin B-subunit (αB-crystallin) and peripherin for further investigation because these proteins were previously reported to be related to central nervous system pathologies. Immunohistochemistry and Western blotting revealed significant upregulation of αB-crystallin and peripherin expression in aged rat spinal cord. Further exploration is needed to elucidate the precise mechanism and potential role of these upregulated proteins in spinal cord aging processes. PMID:28634429

Plasticity and regeneration in the injured spinal cord after cell transplantation therapy.

PubMed

Nori, Satoshi; Nakamura, Masaya; Okano, Hideyuki

2017-01-01

Spinal cord injury (SCI) typically damages the long axonal tracts of the spinal cord which results in permanent disability. However, regeneration of the injured spinal cord is approaching reality according to the advances in stem cell biology. Cell transplantation therapy holds potential to lead to recovery following SCI through some positive mechanisms. Grafted cells induce plasticity and regeneration in the injured spinal cord by promoting remyelination of damaged axons, reconstruction of neural circuits by synapse formation between host neurons and graft-derived neurons, and secreting neurotrophic factors to promote axonal elongation as well as reduce retrograde axonal degeneration. In this review, we will delineate (1) the microenvironment of the injured spinal cord that influence the plasticity and regeneration capacity after SCI, (2) a number of different kinds of cell transplantation therapies for SCI that has been extensively studied by researchers, and (3) potential mechanisms of grafted cell-induced regeneration and plasticity in the injured spinal cord. © 2017 Elsevier B.V. All rights reserved.

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

Quantitative measurement of intervertebral disc signal using MRI.

PubMed

Niemeläinen, R; Videman, T; Dhillon, S S; Battié, M C

2008-03-01

To investigate the spinal cord as an alternative intra-body reference to cerebrospinal fluid (CSF) in evaluating thoracic disc signal intensity. T2-weighted magnetic resonance imaging (MRI) images of T6-T12 were obtained using 1.5 T machines for a population-based sample of 523 men aged 35-70 years. Quantitative data on the signal intensities were acquired using an image analysis program (SpEx). A random sample of 30 subjects and intraclass correlation coefficients (ICC) were used to examine the repeatability of the spinal cord measurements. The validity of using the spinal cord as a reference was examined by correlating cord and CSF samples. Finally, thoracic disc signal was validated by correlating it with age without adjustment and adjusting for either cord or CSF. Pearson's r was used for correlational analyses. The repeatability of the spinal cord signal measurements was extremely high (>or=0.99). The correlations between the signals of spinal cord and CSF by level were all above 0.9. The spinal cord-adjusted disc signal and age correlated similarly with CSF-adjusted disc signal and age (r=-0.30 to -0.40 versus r=-0.26 to -0.36). Adjacent spinal cord is a good alternative reference to the current reference standard, CSF, for quantitative measurements of disc signal intensity. Clearly fewer levels were excluded when using spinal cord as compared to CSF due to missing reference samples.

[Review of the regeneration mechanism of complete spinal cord injury].

PubMed

Li, Jiayin; Li, Xing; Xiao, Zhifeng; Dai, Jianwu

2018-06-01

Spinal cord injury (SCI), especially the complete SCI, usually results in complete paralysis below the level of the injury and seriously affects the patient's quality of life. SCI repair is still a worldwide medical problem. In the last twenty years, Professor DAI Jianwu and his team pioneered complete SCI model by removing spinal tissue with varied lengths in rodents, canine, and non-human primates to verify therapeutic effect of different repair strategies. Moreover, they also started the first clinical study of functional collagen scaffold on patients with acute complete SCI on January 16th, 2015. This review mainly focusses on the possible mechanisms responsible for complete SCI. In common, recovery of some sensory and motor functions post complete SCI include the following three contributing reasons. ① Regeneration of long ascending and descending axons throughout the lesion site to re-connect the original targets; ② New neural circuits formed in the lesion site by newly generated neurons post injury, which effectively re-connect the transected stumps; ③ The combined effect of ① and ②. The numerous studies have confirmed that neural circuits rebuilt across the injury site by newborn neurons might be the main mechanisms for functional recovery of animals from rodents to dogs. In many SCI model, especially the complete spinal cord transection model, many studies have convincingly demonstrated that the quantity and length of regenerated long descending axons, particularly like CST fibers, are too few to across the lesion site that is millimeters in length to realize motor functional recovery. Hence, it is more feasible in guiding neuronal relays formation by bio-scaffolds implantation than directing long motor axons regeneration in improving motor function of animals with complete spinal cord transection. However, some other issues such as promoting more neuronal relays formation, debugging wrong connections, and maintaining adequate neural circuits for functional recovery are urgent problems to be addressed.

Magnetic resonance imaging tractography as a diagnostic tool in patients with spinal cord injury treated with human embryonic stem cells.

PubMed

Shroff, Geeta

2017-02-01

Introduction Spinal cord injury is a cause of severe disability and mortality. The pharmacological and non-pharmacological methods used, are unable to improve the quality of life in spinal cord injury. Spinal disorders have been treated with human embryonic stem cells. Magnetic resonance imaging and tractography were used as imaging modality to document the changes in the damaged cord, but the magnetic resonance imaging tractography was seen to be more sensitive in detecting the changes in the spinal cord. The present study was conducted to evaluate the diagnostic modality of magnetic resonance imaging tractography to determine the efficacy of human embryonic stem cells in chronic spinal cord injury. Materials and methods The study included the patients with spinal cord injury for whom magnetic resonance imaging tractography was performed before and after the therapy. Omniscan (gadodiamide) magnetic resonance imaging tractography was analyzed to assess the spinal defects and the improvement by human embryonic stem cell treatment. The patients were also scored by American Spinal Injury Association scale. Results Overall, 15 patients aged 15-44 years with clinical manifestations of spinal cord injury had magnetic resonance imaging tractography performed. The average treatment period was nine months. The majority of subjects ( n = 13) had American Spinal Injury Association score A, and two patients were at score C at the beginning of therapy. At the end of therapy, 10 patients were at score A, two patients were at score B and three patients were at score C. Improvements in patients were clearly understood through magnetic resonance imaging tractography as well as in clinical signs and symptoms. Conclusion Magnetic resonance imaging tractography can be a crucial diagnostic modality to assess the improvement in spinal cord injury patients.

Cervical spinal stenosis and sports-related cervical cord neurapraxia in children.

PubMed

Boockvar, J A; Durham, S R; Sun, P P

2001-12-15

Congenital spinal stenosis has been demonstrated to contribute to cervical cord neurapraxia after cervical spinal cord injury in adult athletes. A sagittal canal diameter <14 mm and/or a Torg ratio (sagittal diameter of the spinal canal: midcervical sagittal vertebral body diameter) of <0.8 are indicative of significant cervical spinal stenosis. Although sports-related cervical spine injuries are common in children, the role of congenital cervical stenosis in the etiology of these injuries remains unclear. The authors measured the sagittal canal diameter and the Torg ratio in children presenting with cervical cord neurapraxia resulting from sports-related cervical spinal cord injuries to determine the presence of congenital spinal stenosis. A total of 13 children (9 male, 4 female) presented with cervical cord neurapraxia after a sports-related cervical spinal cord injury. Age ranged from 7 to 15 years (mean +/- SD, 11.5 +/- 2.7 years). The sports involved were football (n = 4), wrestling (n = 2), hockey (n = 2), and soccer, gymnastics, baseball, kickball, and pogosticking (n = 1 each). Lateral cervical spine radiographs were used to determine the sagittal canal diameter and the Torg ratio at C4. The sagittal canal diameter (mean +/- SD, 17.58 +/- 1.63 mm) and the Torg ratio (mean +/- SD, 1.20 +/- 0.24) were normal in all of these children. Using the sagittal canal diameter and the Torg ratio as a measurement of congenital spinal stenosis, the authors did not find evidence of congenital cervical spinal stenosis in a group of children with sports-related cervical spinal cord neurapraxia. The occurrence of cervical cord neurapraxia in pediatric patients can be attributed to the mobility of the pediatric spine rather than to congenital cervical spinal stenosis.

Neurological deterioration during intubation in cervical spine disorders

PubMed Central

Durga, Padmaja; Sahu, Barada Prasad

2014-01-01

Anaesthesiologists are often involved in the management of patients with cervical spine disorders. Airway management is often implicated in the deterioration of spinal cord function. Most evidence on neurological deterioration resulting from intubation is from case reports which suggest only association, but not causation. Most anaesthesiologists and surgeons probably believe that the risk of spinal cord injury (SCI) during intubation is largely due to mechanical compression produced by movement of the cervical spine. But it is questionable that the small and brief deformations produced during intubation can produce SCI. Difficult intubation, more frequently encountered in patients with cervical spine disorders, is likely to produce greater movement of spine. Several alternative intubation techniques are shown to improve ease and success, and reduce cervical spine movement but their role in limiting SCI is not studied. The current opinion is that most neurological injuries during anaesthesia are the result of prolonged deformation, impaired perfusion of the cord, or both. To prevent further neurological injury to the spinal cord and preserve spinal cord function, minimizing movement during intubation and positioning for surgery are essential. The features that diagnose laryngoscopy induced SCI are myelopathy present on recovery, short period of unconsciousness, autonomic disturbances following laryngoscopy, cranio-cervical junction disease or gross instability below C3. It is difficult to accept or refute the claim that neurological deterioration was induced by intubation. Hence, a record of adequate care at laryngoscopy and also perioperative period are important in the event of later medico-legal proceedings. PMID:25624530

Human hepatocyte growth factor promotes functional recovery in primates after spinal cord injury.

PubMed

Kitamura, Kazuya; Fujiyoshi, Kanehiro; Yamane, Jun-Ichi; Toyota, Fumika; Hikishima, Keigo; Nomura, Tatsuji; Funakoshi, Hiroshi; Nakamura, Toshikazu; Aoki, Masashi; Toyama, Yoshiaki; Okano, Hideyuki; Nakamura, Masaya

2011-01-01

Many therapeutic interventions for spinal cord injury (SCI) using neurotrophic factors have focused on reducing the area damaged by secondary, post-injury degeneration, to promote functional recovery. Hepatocyte growth factor (HGF), which is a potent mitogen for mature hepatocytes and a mediator of the inflammatory responses to tissue injury, was recently highlighted as a potent neurotrophic factor in the central nervous system. We previously reported that introducing exogenous HGF into the injured rodent spinal cord using a herpes simplex virus-1 vector significantly reduces the area of damaged tissue and promotes functional recovery. However, that study did not examine the therapeutic effects of administering HGF after injury, which is the most critical issue for clinical application. To translate this strategy to human treatment, we induced a contusive cervical SCI in the common marmoset, a primate, and then administered recombinant human HGF (rhHGF) intrathecally. Motor function was assessed using an original open field scoring system focusing on manual function, including reach-and-grasp performance and hand placement in walking. The intrathecal rhHGF preserved the corticospinal fibers and myelinated areas, thereby promoting functional recovery. In vivo magnetic resonance imaging showed significant preservation of the intact spinal cord parenchyma. rhHGF-treatment did not give rise to an abnormal outgrowth of calcitonin gene related peptide positive fibers compared to the control group, indicating that this treatment did not induce or exacerbate allodynia. This is the first study to report the efficacy of rhHGF for treating SCI in non-human primates. In addition, this is the first presentation of a novel scale for assessing neurological motor performance in non-human primates after contusive cervical SCI.

Human Hepatocyte Growth Factor Promotes Functional Recovery in Primates after Spinal Cord Injury

PubMed Central

Kitamura, Kazuya; Fujiyoshi, Kanehiro; Yamane, Jun-ichi; Toyota, Fumika; Hikishima, Keigo; Nomura, Tatsuji; Funakoshi, Hiroshi; Nakamura, Toshikazu; Aoki, Masashi; Toyama, Yoshiaki; Okano, Hideyuki; Nakamura, Masaya

2011-01-01

Many therapeutic interventions for spinal cord injury (SCI) using neurotrophic factors have focused on reducing the area damaged by secondary, post-injury degeneration, to promote functional recovery. Hepatocyte growth factor (HGF), which is a potent mitogen for mature hepatocytes and a mediator of the inflammatory responses to tissue injury, was recently highlighted as a potent neurotrophic factor in the central nervous system. We previously reported that introducing exogenous HGF into the injured rodent spinal cord using a herpes simplex virus-1 vector significantly reduces the area of damaged tissue and promotes functional recovery. However, that study did not examine the therapeutic effects of administering HGF after injury, which is the most critical issue for clinical application. To translate this strategy to human treatment, we induced a contusive cervical SCI in the common marmoset, a primate, and then administered recombinant human HGF (rhHGF) intrathecally. Motor function was assessed using an original open field scoring system focusing on manual function, including reach-and-grasp performance and hand placement in walking. The intrathecal rhHGF preserved the corticospinal fibers and myelinated areas, thereby promoting functional recovery. In vivo magnetic resonance imaging showed significant preservation of the intact spinal cord parenchyma. rhHGF-treatment did not give rise to an abnormal outgrowth of calcitonin gene related peptide positive fibers compared to the control group, indicating that this treatment did not induce or exacerbate allodynia. This is the first study to report the efficacy of rhHGF for treating SCI in non-human primates. In addition, this is the first presentation of a novel scale for assessing neurological motor performance in non-human primates after contusive cervical SCI. PMID:22140459

Neurogenin3 restricts serotonergic neuron differentiation to the hindbrain.

PubMed

Carcagno, Abel L; Di Bella, Daniela J; Goulding, Martyn; Guillemot, Francois; Lanuza, Guillermo M

2014-11-12

The development of the nervous system is critically dependent on the production of functionally diverse neuronal cell types at their correct locations. In the embryonic neural tube, dorsoventral signaling has emerged as a fundamental mechanism for generating neuronal diversity. In contrast, far less is known about how different neuronal cell types are organized along the rostrocaudal axis. In the developing mouse and chick neural tube, hindbrain serotonergic neurons and spinal glutamatergic V3 interneurons are produced from ventral p3 progenitors, which possess a common transcriptional identity but are confined to distinct anterior-posterior territories. In this study, we show that the expression of the transcription factor Neurogenin3 (Neurog3) in the spinal cord controls the correct specification of p3-derived neurons. Gain- and loss-of-function manipulations in the chick and mouse embryo show that Neurog3 switches ventral progenitors from a serotonergic to V3 differentiation program by repressing Ascl1 in spinal p3 progenitors through a mechanism dependent on Hes proteins. In this way, Neurog3 establishes the posterior boundary of the serotonergic system by actively suppressing serotonergic specification in the spinal cord. These results explain how equivalent p3 progenitors within the hindbrain and the spinal cord produce functionally distinct neuron cell types. Copyright © 2014 the authors 0270-6474/14/3415223-11$15.00/0.

Neuropeptide Y in human spinal cord.

PubMed

Allen, J M; Gibson, S J; Adrian, T E; Polak, J M; Bloom, S R

1984-08-06

The distribution of a newly described peptide, neuropeptide Y (NPY) within the human spinal cord has been determined using radioimmunoassay and immunocytochemistry. Higher concentrations were found in the lumbar (49.9 +/- 6.8 pmol/g) and sacral (47.0 +/- 10.6 pmol/g) regions than in the cervical (27.6 +/- 2.7 pmol/g) and thoracic spinal cord (33.8 +/- 5.3 pmol/g). Immunocytochemistry revealed numerous nerve fibers containing NPY in the spinal cord; these were particularly concentrated in the substantia gelatinosa of the dorsal horn. In the ventral spinal cord NPY-containing nerves were sparse becoming more abundant in lumbosacral segments.

Focal dysfunction of the proteasome: a pathogenic factor in a mouse model of amyotrophic lateral sclerosis.

PubMed

Kabashi, Edor; Agar, Jeffrey N; Taylor, David M; Minotti, Sandra; Durham, Heather D

2004-06-01

Mutations in the Cu/Zn-superoxide dismutase (SOD-1) gene are responsible for a familial form of amyotrophic lateral sclerosis (fALS). The present study demonstrated impaired proteasomal function in the lumbar spinal cord of transgenic mice expressing human SOD-1 with the ALS-causing mutation G93A (SOD-1(G93A)) compared to non-transgenic littermates (LM) and SOD-1(WT) transgenic mice. Chymotrypsin-like activity was decreased as early as 45 days of age. By 75 days, chymotrypsin-, trypsin-, and caspase-like activities of the proteasome were impaired, at about 50% of control activity in lumbar spinal cord, but unchanged in thoracic spinal cord and liver. Both total and specific activities of the proteasome were reduced to a similar extent, indicating that a change in proteasome function, rather than a decrease in proteasome levels, had occurred. Similar decreases of total and specific activities of the proteasome were observed in NIH 3T3 cell lines expressing fALS mutants SOD-1(G93A) and SOD-1(G41S), but not in SOD-1(WT) controls. Although overall levels of proteasome were maintained in spinal cord of SOD-1(G93A) transgenic mice, the level of 20S proteasome was substantially reduced in lumbar spinal motor neurons relative to the surrounding neuropil. It is concluded that impairment of the proteasome is an early event and contributes to ALS pathogenesis.

Relationship of life satisfaction to impairment, disability, and handicap among persons with spinal cord injury living in the community.

PubMed

Fuhrer, M J; Rintala, D H; Hart, K A; Clearman, R; Young, M E

1992-06-01

The level and correlates of the life satisfaction of persons with spinal cord injury who are residing in the community were investigated. One hundred men and 40 women were chosen randomly from a cohort of 640 persons with spinal cord injury residing in a 13-county area in southeast Texas. The mean Life Satisfaction Index-A (LSIA-A) was lower than reported previously for persons in the general population. The LSIA-A was not correlated significantly with chronologic variables, the ASIA Total Motor Index Score, or a self-report version of the Functional Independence Measure. The LSIA-A was associated positively with self-assessed health, perceived control, and social support, as well as with the Social Integration, Occupation, and Mobility dimensions of the Craig Handicap Assessment and Reporting Technique. From the standpoint of an augmented version of the World Health Organization model of disablement, the life satisfaction of persons with spinal cord injury appears to be influenced, albeit indirectly, by selective aspects of their social role performance (handicap), but not by their degree of impairment or disability.

Quantitative aspects of the clinical performance of transverse tripolar spinal cord stimulation.

PubMed

Wesselink, W A; Holsheimer, J; King, G W; Torgerson, N A; Boom, H B

1999-01-01

A multicenter study was initiated to evaluate the performance of the transverse tripolar system for spinal cord stimulation. Computer modeling had predicted steering of paresthesia with a dual channel stimulator to be the main benefit of the system. The quantitative analysis presented here includes the results of 484 tests in 30 patients. For each test, paresthesia coverage as a function of voltage levels was stored in a computerized database, including a body map which enabled calculation of the degree of paresthesia coverage of separate body areas, as well as the overlap with the painful areas. The results show that with the transverse tripolar system steering of the paresthesia is possible, although optimal steering requires proper placement of the electrode with respect to the spinal cord. Therefore, with this steering ability as well as a larger therapeutic stimulation window as compared to conventional systems, we expect an increase of the long-term efficacy of spinal cord stimulation. Moreover, in view of the stimulation-induced paresthesia patterns, the system allows selective stimulation of the medial dorsal columns.

Gene Delivery Strategies to Promote Spinal Cord Repair

PubMed Central

Walthers, Christopher M; Seidlits, Stephanie K

2015-01-01

Gene therapies hold great promise for the treatment of many neurodegenerative disorders and traumatic injuries in the central nervous system. However, development of effective methods to deliver such therapies in a controlled manner to the spinal cord is a necessity for their translation to the clinic. Although essential progress has been made to improve efficiency of transgene delivery and reduce the immunogenicity of genetic vectors, there is still much work to be done to achieve clinical strategies capable of reversing neurodegeneration and mediating tissue regeneration. In particular, strategies to achieve localized, robust expression of therapeutic transgenes by target cell types, at controlled levels over defined time periods, will be necessary to fully regenerate functional spinal cord tissues. This review summarizes the progress over the last decade toward the development of effective gene therapies in the spinal cord, including identification of appropriate target genes, improvements to design of genetic vectors, advances in delivery methods, and strategies for delivery of multiple transgenes with synergistic actions. The potential of biomaterials to mediate gene delivery while simultaneously providing inductive scaffolding to facilitate tissue regeneration is also discussed. PMID:25922572

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.

Spinal cord evoked magnetic field measurement using a magnetospinography system equipped with a cryocooler.

PubMed

Adachi, Yoshiaki; Oyama, Daisuke; Kawai, Jun; Kawabata, Shigenori; Uehara, Gen

2013-01-01

We have developed a magnetospinography (MSG) system that detects weak magnetic fields associated with spinal cord neural activity using an array of low-temperature superconducting quantum interference device (SQUID)-based magnetic flux sensors. A functional image of the spinal cord can be obtained noninvasively by using this system, and it is effective for precise lesion localization in the diagnosis of spinal cord diseases. The running cost of the developed MSG system mainly depends on liquid helium (LHe) consumption, which is required to maintain the superconducting state of the SQUID sensors. To reduce the LHe consumption, we incorporate a pulse-tube-refrigerator-based cryocooler into the MSG system. Cold gaseous helium is circulated between the cryocooler and the MSG system for cooling the thermal radiation shield of the dewar vessel. Consequently, we achieved a 46% decrease in the LHe consumption rate. Conventional biomagnetic field detection such as magnetoencephalography is often hindered by severe low-frequency band noise from the cryocooler. However, in the case of MSG measurements, such noise can be filtered out because the band of the signal is much higher than that of the cryocooler noise. We demonstrated that the signal-to-noise ratio of the cervical spinal cord evoked magnetic field measurement performed with a working cryocooler is comparable to that of the measurement without a cryocooler.

Pelvic floor muscle training in spinal cord injury and its impact on neurogenic detrusor over-activity and incontinence.

PubMed

Vásquez, N; Knight, S L; Susser, J; Gall, A; Ellaway, P H; Craggs, M D

2015-12-01

Two case studies. To determine whether 6 weeks of regular pelvic floor muscle training (PFMT) can improve the strength and endurance of voluntary contractions in incomplete spinal cord injury and reduce neurogenic detrusor over-activity (NDO) and incontinence. The London Spinal Cord Injury Centre, Stanmore, London, UK. A 6-week programme of PFMT was conducted in two male subjects with stable supra-sacral motor incomplete (AIS C and D) spinal cord injuries. Clinical evaluations before and after training comprised measures of strength and endurance of voluntary pelvic floor contractions both objectively by anal canal-pressure measurements and subjectively using the modified Oxford grading system. NDO was determined by standard urodynamic tests of bladder function and incontinence measured by the International Consultation on Incontinence Questionnaire-Urology. Both subjects improved the strength and endurance of their pelvic floor muscle contractions by over 100% at the end of training. After training, Subject 1 (AIS D) was able to reduce bladder pressure during over-activity almost completely by voluntarily contracting the pelvic floor muscles. Subject 2 (AIS C) achieved a lesser reduction overall after training. Continence improved only in subject 1. These case studies provide evidence that a 6-week programme of PFMT may have a beneficial effect on promoting voluntary control of NDO and reduce incontinence in selected cases with a motor incomplete spinal cord lesion.

Complete reorganization of the motor cortex of adult rats following long-term spinal cord injuries.

PubMed

Tandon, Shashank; Kambi, Niranjan; Mohammed, Hisham; Jain, Neeraj

2013-07-01

Understanding brain reorganization following long-term spinal cord injuries is important for optimizing recoveries based on residual function as well as developing brain-controlled assistive devices. Although it has been shown that the motor cortex undergoes partial reorganization within a few weeks after peripheral and spinal cord injuries, it is not known if the motor cortex of rats is capable of large-scale reorganization after longer recovery periods. Here we determined the organization of the rat (Rattus norvegicus) motor cortex at 5 or more months after chronic lesions of the spinal cord at cervical levels using intracortical microstimulation. The results show that, in the rats with the lesions, stimulation of neurons in the de-efferented forelimb motor cortex no longer evokes movements of the forelimb. Instead, movements of the body parts in the adjacent representations, namely the whiskers and neck were evoked. In addition, at many sites, movements of the ipsilateral forelimb were observed at threshold currents. The extent of representations of the eye, jaw and tongue movements was unaltered by the lesion. Thus, large-scale reorganization of the motor cortex leads to complete filling-in of the de-efferented cortex by neighboring representations following long-term partial spinal cord injuries at cervical levels in adult rats. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Glycogen synthase kinase-3 beta inhibition reduces secondary damage in experimental spinal cord trauma.

PubMed

Cuzzocrea, Salvatore; Genovese, Tiziana; Mazzon, Emanuela; Crisafulli, Concetta; Di Paola, Rosanna; Muià, Carmelo; Collin, Marika; Esposito, Emanuela; Bramanti, Placido; Thiemermann, Christoph

2006-07-01

Glycogen synthase kinase-3 (GSK-3) has recently been identified as an ubiquitous serine-threonine protein kinase that participates in a multitude of cellular processes and plays an important role in the pathophysiology of a number of diseases. The aim of this study was to investigate the effects of GSK-3beta inhibition on the degree of experimental spinal cord trauma induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. Spinal cord injury (SCI) in mice resulted in severe trauma characterized by edema, neutrophil infiltration, production of a range of inflammatory mediators, tissue damage, and apoptosis. Treatment of the mice with 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), a potent and selective GSK-3beta inhibitor, significantly reduced the degree of 1) spinal cord inflammation and tissue injury (histological score); 2) neutrophil infiltration (myeloperoxidase activity); 3) inducible nitric-oxide synthase, nitrotyrosine, and cyclooxygenase-2 expression; and 4) and apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and Bax and Bcl-2 expression). In a separate set of experiments, TDZD-8 significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with TDZD-8 reduces the development of inflammation and tissue injury associated with spinal cord trauma.

Metastatic Spinal Cord Compression from Non-Small-Cell Lung Cancer Treated with Surgery and Adjuvant Therapies: A Retrospective Analysis of Outcomes and Prognostic Factors in 116 Patients.

PubMed

Tang, Yu; Qu, Jintao; Wu, Juan; Li, Song; Zhou, Yue; Xiao, Jianru

2015-09-02

Metastatic spinal cord compression is a disastrous consequence of non-small-cell lung cancer (NSCLC). There have been few studies of the outcomes or prognostic factors in patients with metastatic spinal cord compression from NSCLC treated with surgery and adjuvant therapies. From 2002 to 2013, 116 patients with metastatic spinal cord compression from NSCLC treated with surgery and adjuvant therapies were enrolled in this retrospective analysis. Kaplan-Meier methods and Cox regression analysis were used to estimate overall survival and identify prognostic factors for survival. Multivariate analysis suggested that the Eastern Cooperative Oncology Group performance status (ECOG-PS), preoperative and postoperative Frankel scores, postoperative adjuvant radiation therapy, and target therapy were independent prognostic factors. Ninety patients died at a median of twelve months (range, three to forty-seven months) postoperatively, and twenty-six patients were still alive at the time of final follow-up (at a median of fifteen months [range, five to fifty-four months]). The complete disappearance of deficits in spinal cord function after surgery was the most robust predictor of survival. Adjuvant radiation therapy and target therapy were also associated with a better prognosis. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Stress-resistant neural stem cells positively influence regional energy metabolism after spinal cord injury in mice.

PubMed

Schwerdtfeger, Karsten; Mautes, Angelika E M; Bernreuther, Christian; Cui, Yifang; Manville, Jérôme; Dihné, Marcel; Blank, Simon; Schachner, Melitta

2012-02-01

The importance of stem cells to ameliorate the devastating consequences of traumatic injuries in the adult mammalian central nervous system calls for improvements in the capacity of these cells to cope, in particular, with the host response to the injury. We have previously shown, however, that in the acutely traumatized spinal cord local energy metabolism led to decreased ATP levels after neural stem cell (NSC) transplantation. As this might counteract NSC-mediated regenerative processes, we investigated if NSC selected for increased oxidative stress resistance are better suited to preserve local energy content. For this purpose, we exposed wild-type (WT) NSC to hydrogen peroxide prior to transplantation. We demonstrate here that transplantation of WT-NSC into a complete spinal cord compression injury model even lowers the ATP content beyond the level detected in spinal cord injury-control animals. Compared to WT-NSC, stress-resistant (SR) NSC did not lead to a further decrease in ATP content. These differences between WT- and SR-NSC were observed 4 h after the lesion with subsequent transplantation. At 24 h after lesioning, these differences were no more as obvious. Thus, in contrast to native NSC, transplantation of NSC selected for oxidative stress resistance can positively influence local energy metabolism in the first hours after spinal cord compression. The functional relevance of this observation has to be tested in further experiments.

Injectable Hydrogels for Spinal Cord Repair: A Focus on Swelling and Intraspinal Pressure.

PubMed

Khaing, Zin Z; Ehsanipour, Arshia; Hofstetter, Christoph P; Seidlits, Stephanie K

Spinal cord injury (SCI) is a devastating condition that leaves patients with limited motor and sensory function at and below the injury site, with little to no hope of a meaningful recovery. Because of their ability to mimic multiple features of central nervous system (CNS) tissues, injectable hydrogels are being developed that can participate as therapeutic agents in reducing secondary injury and in the regeneration of spinal cord tissue. Injectable biomaterials can provide a supportive substrate for tissue regeneration, deliver therapeutic factors, and regulate local tissue physiology. Recent reports of increasing intraspinal pressure after SCI suggest that this physiological change can contribute to injury expansion, also known as secondary injury. Hydrogels contain high water content similar to native tissue, and many hydrogels absorb water and swell after formation. In the case of injectable hydrogels for the spinal cord, this process often occurs in or around the spinal cord tissue, and thus may affect intraspinal pressure. In the future, predictable swelling properties of hydrogels may be leveraged to control intraspinal pressure after injury. Here, we review the physiology of SCI, with special attention to the current clinical and experimental literature, underscoring the importance of controlling intraspinal pressure after SCI. We then discuss how hydrogel fabrication, injection, and swelling can impact intraspinal pressure in the context of developing injectable biomaterials for SCI treatment. © 2016 S. Karger AG, Basel.

Local delivery of thyroid hormone enhances oligodendrogenesis and myelination after spinal cord injury

NASA Astrophysics Data System (ADS)

Shultz, Robert B.; Wang, Zhicheng; Nong, Jia; Zhang, Zhiling; Zhong, Yinghui

2017-06-01

Objective. Traumatic spinal cord injury (SCI) causes apoptosis of myelin-forming oligodendrocytes (OLs) and demyelination of surviving axons, resulting in conduction failure. Remyelination of surviving denuded axons provides a promising therapeutic target for spinal cord repair. While cell transplantation has demonstrated efficacy in promoting remyelination and functional recovery, the lack of ideal cell sources presents a major obstacle to clinical application. The adult spinal cord contains oligodendrocyte precursor cells and multipotent neural stem/progenitor cells that have the capacity to differentiate into mature, myelinating OLs. However, endogenous oligodendrogenesis and remyelination processes are limited by the upregulation of remyelination-inhibitory molecules in the post-injury microenvironment. Multiple growth factors/molecules have been shown to promote OL differentiation and myelination. Approach. In this study we screened these therapeutics and found that 3, 3‧, 5-triiodothyronine (T3) is the most effective in promoting oligodendrogenesis and OL maturation in vitro. However, systemic administration of T3 to achieve therapeutic doses in the injured spinal cord is likely to induce hyperthyroidism, resulting in serious side effects. Main results. In this study we developed a novel hydrogel-based drug delivery system for local delivery of T3 to the injury site without eliciting systemic toxicity. Significance. Using a clinically relevant cervical contusion injury model, we demonstrate that local delivery of T3 at doses comparable to safe human doses promoted new mature OL formation and myelination after SCI.

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.

A Review on Locomotor Training after Spinal Cord Injury: Reorganization of Spinal Neuronal Circuits and Recovery of Motor Function

PubMed Central

2016-01-01

Locomotor training is a classic rehabilitation approach utilized with the aim of improving sensorimotor function and walking ability in people with spinal cord injury (SCI). Recent studies have provided strong evidence that locomotor training of persons with clinically complete, motor complete, or motor incomplete SCI induces functional reorganization of spinal neuronal networks at multisegmental levels at rest and during assisted stepping. This neuronal reorganization coincides with improvements in motor function and decreased muscle cocontractions. In this review, we will discuss the manner in which spinal neuronal circuits are impaired and the evidence surrounding plasticity of neuronal activity after locomotor training in people with SCI. We conclude that we need to better understand the physiological changes underlying locomotor training, use physiological signals to probe recovery over the course of training, and utilize established and contemporary interventions simultaneously in larger scale research studies. Furthermore, the focus of our research questions needs to change from feasibility and efficacy to the following: what are the physiological mechanisms that make it work and for whom? The aforementioned will enable the scientific and clinical community to develop more effective rehabilitation protocols maximizing sensorimotor function recovery in people with SCI. PMID:27293901

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.

Does consumption of polyunsaturated fatty acids influence on neurorehabilitation in traumatic spinal cord-injured individuals? A double-blinded clinical trial.

PubMed

Norouzi Javidan, A; Sabour, H; Latifi, S; Abrishamkar, M; Soltani, Z; Shidfar, F; Emami Razavi, H

2014-05-01

A double-blinded randomized clinical trial. The anti-inflammatory and neuroprotective effect of omega-3 fatty acids have been shown so far, but still its influence on clinical measures in spinal cord-injured human models were not known. We tried to investigate changes in disability and dependency scores in chronic traumatic spinal cord-injured patients after 14 months of ω-3 fatty-acid consumption. Main inclusion criteria were: traumatic spinal cord injury (SCI) and post injury duration longer than 1 year. Disability and dependency was assessed using U.K Functional Independence Measure and Functional Assessment Measure (FIM+FAM) scale. MorDHA capsules (435 mg of docosahexaenoic acid and 65 mg of eicosapentaenoic acid) were administered in treatment group, whereas control group received placebo capsules for 14 months. U.K. FIM+FAM scale were estimated before intervention and at the end of the trial. Fifty-four patients in treatment group and 50 patients in placebo group completed the trial. Highest scores were detected in cognitive domain in both groups before and after intervention. Most dependency was observed in locomotion subscale and secondly in sphincter control. Scores of none of these components were changed by ω-3 fatty-acid consumption. Although omega-3 fatty acids have been shown to have neuroprotective effect in acute phase of SCI, it seems that they have no significant influence in chronic inflammatory state of SCI. The positive effect of ω-3 fatty acid in chronic neurorecovery process, if exists, is weaker to exert any significant improvement in UK FIM+FAM scores in spinal cord-injured individuals.

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

Mangiferin attenuates contusive spinal cord injury in rats through the regulation of oxidative stress, inflammation and the Bcl‑2 and Bax pathway.

PubMed

Luo, Yang; Fu, Changfeng; Wang, Zhenyu; Zhang, Zhuo; Wang, Hongxia; Liu, Yi

2015-11-01

Mangiferin has antioxidant, antiviral, apoptosis regulating, anti‑inflammatory, antitumor and antidiabetic effects, which can also inhibit osteoclast formation and bone resorption. However, whether mangiferin ameliorates the neurological pain of spinal cord injury (SCI) in ratS remains to be elucidated. The present study investigated the therapeutic effects of mangiferin on neurological function, the water content of spinal cord, oxidative stress, the expression of inflammatory cytokines and the protein expression of Bcl‑2/Bax in a SCI rat model. In the present study, the Basso, Beattie and Bresnahan scores, and the water content of the spinal cord were used to analyze the therapeutic effects of mangiferin on neurological pain in the SCI rat. The concentrations of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and the serum levels of glutathione peroxidase (GSH‑PX), nuclear factor‑κB p65 unit, tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6 and caspase‑3/9 were detected using commercial kits. The expression levels of Bcl‑2 and Bax were measured using western blot analysis. The results demonstrated that administrating mangiferin began to ameliorate neurological function and the water content of the spinal cord in the SCI rat. The mangiferin‑treated group were found to have lower oxidative stress activity and lower expression levels of inflammatory cytokines, compared with the SCI rat. In addition, mangiferin significantly reduced the protein expression of Bax and promoted the protein expression of Bcl-2 in the SCI rat model. Finally, mangiferin markedly suppressed the expression of caspase‑3/9, indicating that the protective action of mangiferin may be associated with anti‑apoptosis activation. In conclusion, mangiferin attenuated contusive SCI in the rats through regulating oxidative stress, inflammation and the Bcl‑2 and Bax pathway.

Nerve growth factor delivery by ultrasound-mediated nanobubble destruction as a treatment for acute spinal cord injury in rats

PubMed Central

Song, Zhaojun; Wang, Zhigang; Shen, Jieliang; Xu, Shengxi; Hu, Zhenming

2017-01-01

Background Spinal cord injuries (SCIs) can cause severe disability or death. Treatment options include surgical intervention, drug therapy, and stem cell transplantation. However, the efficacy of these methods for functional recovery remains unsatisfactory. Purpose This study was conducted to explore the effect of ultrasound (US)-mediated destruction of poly(lactic-co-glycolic acid) (PLGA) nanobubbles (NBs) expressing nerve growth factor (NGF) (NGF/PLGA NBs) on nerve regeneration in rats following SCI. Materials and methods Adult male Sprague Dawley rats were randomly divided into four treatment groups after Allen hit models of SCI were established. The groups were normal saline (NS) group, NGF and NBs group, NGF and US group, and NGF/PLGA NBs and US group. Histological changes after SCI were observed by hematoxylin and eosin staining. Neuron viability was determined by Nissl staining. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining was used to examine cell apoptosis. NGF gene and protein expressions were detected by quantitative reverse transcription polymerase chain reaction and Western blotting. Green fluorescent protein expression in the spinal cord was examined using an inverted fluorescence microscope. The recovery of neural function was determined using the Basso, Beattie, and Bresnahan test. Results NGF therapy using US-mediated NGF/PLGA NBs destruction significantly increased NGF expression, attenuated histological injury, decreased neuron loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in rats with SCI. Conclusion US-mediated NGF/PLGA NBs destruction effectively transfects the NGF gene into target tissues and has a significant effect on the injured spinal cord. The combination of US irradiation and gene therapy through NGF/PLGA NBs holds great promise for the future of nanomedicine and the development of noninvasive treatment options for SCI and other diseases. PMID:28280337

Rehabilitation R&D Progress Reports 1995, Volume 33, June 1996

DTIC Science & Technology

1996-06-01

Stimulation 72 Rehabilitation of the Colon after Spinal Cord Injury: A Pilot Study 73 Electrical Control of Bladder and Bowel following Spinal Cord Injury...A. General 130 Design of New Toilet Prototypes for Elderly and Disabled Veterans 131 Design of a New Bowel Care/Shower Chair for SCI Veterans...and Rehabilitation 292 Functional Restoration of Grasp: A Pilot Study 293 High-Frequency Magnetic Stimulation of the Bladder and Bowel 294 Treatment

A Multicenter, Randomized Controlled Trial of Cerebrospinal Fluid Drainage in Acute Spinal Cord Injury

DTIC Science & Technology

2015-10-01

Injury PRINCIPAL INVESTIGATOR: Nicholas Theodore, MD CONTRACTING ORGANIZATION: Dignity Health San Francisco, CA 94107-1773 REPORT DATE: October 2015...TASK NUMBER E-Mail: Nicholas.Theodore@bnaneuro.net 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Dignity Health AND ADDRESS...patients aims to reduce cell death and axonal damage leading to improved neurological function in patients. 2. KEYWORDS acute spinal cord injury

Effects of Enhanced Oxygen Delivery by Perfluorocarbons in Spinal Cord Injury

DTIC Science & Technology

2013-01-01

spinal cord ischemia. Acta Med Okayama 1997; 51:71–77. 10. Daugherty WP, Levasseur JE, Sun D, Spiess BD, Bullock MR: Perfluorocarbon emulsion improves...cerebral oxygenation and mitochondrial function after fluid percussion brain injury in rats. Neurosurgery 2004; 54:1223–1230. 11. Spiess B...2008; 2: 213-20. 13. Zhou Z, Sun D, Levasseur JE, Merenda A, Hamm RJ, Zhu J, Spiess BD, Bullock MR. Perfluorocarbon emulsions improve cognitive

Effects of aquatic exercise on physical function and fitness among people with spinal cord injury

PubMed Central

Li, Chunxiao; Khoo, Selina; Adnan, Athirah

2017-01-01

Abstract Objective: The aim of this review is to synthesize the evidence on the effects of aquatic exercise interventions on physical function and fitness among people with spinal cord injury. Data source: Six major databases were searched from inception till June 2015: MEDLINE, CINAHL, EMBASE, PsychInfo, SPORTDiscus, and Cochrane Center Register of Controlled Trials. Study appraisal and synthesis methods: Two reviewers independently rated methodological quality using the modified Downs and Black Scale and extracted and synthesized key findings (i.e., participant characteristics, study design, physical function and fitness outcomes, and adverse events). Results: Eight of 276 studies met the inclusion criteria, of which none showed high research quality. Four studies assessed physical function outcomes and 4 studies evaluated aerobic fitness as outcome measures. Significant improvements on these 2 outcomes were generally found. Other physical or fitness outcomes including body composition, muscular strength, and balance were rarely reported. Conclusions and implications of key findings: There is weak evidence supporting aquatic exercise training to improve physical function and aerobic fitness among adults with spinal cord injury. Suggestions for future research include reporting details of exercise interventions, evaluating other physical or fitness outcomes, and improving methodological quality. PMID:28296754

A Toll-Like Receptor 9 Antagonist Improves Bladder Function and White Matter Sparing in Spinal Cord Injury

PubMed Central

David, Brian T.; Sampath, Sujitha; Dong, Wei; Heiman, Adee; Rella, Courtney E.; Elkabes, Stella

2014-01-01

Abstract Spinal cord injury (SCI) affects motor, sensory, and autonomic functions. As current therapies do not adequately alleviate functional deficits, the development of new and more effective approaches is of critical importance. Our earlier investigations indicated that intrathecal administration of a toll-like receptor 9 (TLR9) antagonist, cytidine-phosphate-guanosine oligodeoxynucleotide 2088 (CpG ODN 2088), to mice sustaining a severe, mid-thoracic contusion injury diminished neuropathic pain but did not alter locomotor deficits. These changes were paralleled by a decrease in the pro-inflammatory response at the injury epicenter. Using the same SCI paradigm and treatment regimen, the current studies investigated the effects of the TLR9 antagonist on bladder function. We report that the TLR9 antagonist decreases SCI-elicited urinary retention and ameliorates bladder morphopathology without affecting kidney function. A significant improvement in white matter sparing was also observed, most likely due to alterations in the inflammatory milieu. These findings indicate that the TLR9 antagonist has beneficial effects not only in reducing sensory deficits, but also on bladder dysfunction and tissue preservation. Thus, modulation of innate immune receptor signaling in the spinal cord can impact the effects of SCI. PMID:24936867

A toll-like receptor 9 antagonist improves bladder function and white matter sparing in spinal cord injury.

PubMed

David, Brian T; Sampath, Sujitha; Dong, Wei; Heiman, Adee; Rella, Courtney E; Elkabes, Stella; Heary, Robert F

2014-11-01

Spinal cord injury (SCI) affects motor, sensory, and autonomic functions. As current therapies do not adequately alleviate functional deficits, the development of new and more effective approaches is of critical importance. Our earlier investigations indicated that intrathecal administration of a toll-like receptor 9 (TLR9) antagonist, cytidine-phosphate-guanosine oligodeoxynucleotide 2088 (CpG ODN 2088), to mice sustaining a severe, mid-thoracic contusion injury diminished neuropathic pain but did not alter locomotor deficits. These changes were paralleled by a decrease in the pro-inflammatory response at the injury epicenter. Using the same SCI paradigm and treatment regimen, the current studies investigated the effects of the TLR9 antagonist on bladder function. We report that the TLR9 antagonist decreases SCI-elicited urinary retention and ameliorates bladder morphopathology without affecting kidney function. A significant improvement in white matter sparing was also observed, most likely due to alterations in the inflammatory milieu. These findings indicate that the TLR9 antagonist has beneficial effects not only in reducing sensory deficits, but also on bladder dysfunction and tissue preservation. Thus, modulation of innate immune receptor signaling in the spinal cord can impact the effects of SCI.

Early changes in muscle atrophy and muscle fiber type conversion after spinal cord transection and peripheral nerve transection in rats.

PubMed

Higashino, Kosaku; Matsuura, Tetsuya; Suganuma, Katsuyoshi; Yukata, Kiminori; Nishisho, Toshihiko; Yasui, Natsuo

2013-05-20

Spinal cord transection and peripheral nerve transection cause muscle atrophy and muscle fiber type conversion. It is still unknown how spinal cord transection and peripheral nerve transection each affect the differentiation of muscle fiber type conversion mechanism and muscle atrophy. The aim of our study was to evaluate the difference of muscle weight change, muscle fiber type conversion, and Peroxisome proliferator-activated receptor-γ coactivatior-1α (PGC-1α) expression brought about by spinal cord transection and by peripheral nerve transection. Twenty-four Wistar rats underwent surgery, the control rats underwent a laminectomy; the spinal cord injury group underwent a spinal cord transection; the denervation group underwent a sciatic nerve transection. The rats were harvested of the soleus muscle and the TA muscle at 0 week, 1 week and 2 weeks after surgery. Histological examination was assessed using hematoxylin and eosin (H&E) staining and immunofluorescent staing. Western blot was performed with 3 groups. Both sciatic nerve transection and spinal cord transection caused muscle atrophy with the effect being more severe after sciatic nerve transection. Spinal cord transection caused a reduction in the expression of both sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection produced an increase in expression of sMHC protein and PGC-1α protein in the soleus muscle. The results of the expression of PGC-1α were expected in other words muscle atrophy after sciatic nerve transection is less than after spinal cord transection, however muscle atrophy after sciatic nerve transection was more severe than after spinal cord transection. In the conclusion, spinal cord transection diminished the expression of sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection enhanced the expression of sMHC protein and PGC-1α protein in the soleus muscle.

Neurotrophic factors and receptors in the immature and adult spinal cord after mechanical injury or kainic acid.

PubMed

Widenfalk, J; Lundströmer, K; Jubran, M; Brene, S; Olson, L

2001-05-15

Delivery of neurotrophic factors to the injured spinal cord has been shown to stimulate neuronal survival and regeneration. This indicates that a lack of sufficient trophic support is one factor contributing to the absence of spontaneous regeneration in the mammalian spinal cord. Regulation of the expression of neurotrophic factors and receptors after spinal cord injury has not been studied in detail. We investigated levels of mRNA-encoding neurotrophins, glial cell line-derived neurotrophic factor (GDNF) family members and related receptors, ciliary neurotrophic factor (CNTF), and c-fos in normal and injured spinal cord. Injuries in adult rats included weight-drop, transection, and excitotoxic kainic acid delivery; in newborn rats, partial transection was performed. The regulation of expression patterns in the adult spinal cord was compared with that in the PNS and the neonate spinal cord. After mechanical injury of the adult rat spinal cord, upregulations of NGF and GDNF mRNA occurred in meningeal cells adjacent to the lesion. BDNF and p75 mRNA increased in neurons, GDNF mRNA increased in astrocytes close to the lesion, and GFRalpha-1 and truncated TrkB mRNA increased in astrocytes of degenerating white matter. The relatively limited upregulation of neurotrophic factors in the spinal cord contrasted with the response of affected nerve roots, in which marked increases of NGF and GDNF mRNA levels were observed in Schwann cells. The difference between the ability of the PNS and CNS to provide trophic support correlates with their different abilities to regenerate. Kainic acid delivery led to only weak upregulations of BDNF and CNTF mRNA. Compared with several brain regions, the overall response of the spinal cord tissue to kainic acid was weak. The relative sparseness of upregulations of endogenous neurotrophic factors after injury strengthens the hypothesis that lack of regeneration in the spinal cord is attributable at least partly to lack of trophic support.

Characterization and regulation of (/sup 3/H)-serotonin uptake and release in rodent spinal

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

Stauderman, K.A.

1986-01-01

The uptake and release of (/sup 3/H)-serotonin were investigated in rat spinal cord synaptosomes. In the uptake experiments, sodium-dependent and sodium-independent (/sup 3/H)-serotonin accumulation processes were found. Sodium-dependent (/sup 3/H)-serotonin accumulation was: linear with sodium concentrations up to 180 mM; decreased by disruption of membrane integrity or ionic gradients; associated with purified synaptosomal fractions; and reduced after description of descending serotonergic neurons in the spinal cord. Of the uptake inhibitors tested, the most potent was fluoxetine (IC/sub 50/ 75 nM), followed by desipramine (IC/sub 50/ 430 nM) and nomifensine (IC/sub 50/ 950 nM). The sodium-independent (/sup 3/H)-serotonin accumulation process wasmore » insensitive to most treatments and probably represents nonspecific membrane binding. Thus, only sodium-dependent (/sup 3/H)-serotonin uptake represents the uptake process of serotonergic nerve terminals in rat spinal cord homogenates. In the release experiments, K/sup +/-induced release of previously accumulated (/sup 3/H)-serotonin was Ca/sup 2 +/-dependent, and originated from serotonergic synaptosomes. Exogenous serotonin and 5-methyoxy-N,N-dimethyltryptamine inhibited (/sup 3/H)-serotonin release in a concentration-dependent way. Of the antagonists tested, only methiothepin effectively blocked the effect of serotonin. These data support the existence of presynaptic serotonin autoreceptors on serotonergic nerve terminals in the rat spinal cord that act to inhibit a voltage and Ca/sup 2 +/-sensitive process linked to serotonin release. Alteration of spinai cord serotonergic function may therefore be possible by drugs acting on presynaptic serotonin autoreceptors in the spinal cord.« less

Extending technology-aided leisure and communication programs to persons with spinal cord injury and post-coma multiple disabilities.

PubMed

Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Sigafoos, Jeff; Ricciuti, Riccardo A; Trignani, Roberto; Oliva, Doretta; Signorino, Mario; D'Amico, Fiora; Sasanelli, Giovanni

2015-01-01

These two studies extended technology-aided programs to promote leisure and communication opportunities to a man with cervical spinal cord injury and a post-coma man with multiple disabilities. The studies involved the use of ABAB designs, in which A and B represented baseline and intervention phases, respectively. The programs focused on enabling the participants to activate songs, videos, requests, text messages, and telephone calls. These options were presented on a computer screen and activated through a small pressure microswitch by the man with spinal cord injury and a special touch screen by the post-coma man. To help the latter participant, who had no verbal skills, with requests and telephone calls, series of words and phrases were made available that he could activate in those situations. Data showed that both participants were successful in managing the programs arranged for them. The man with spinal cord injury activated mean frequencies of above five options per 10-min session. The post-coma man activated mean frequencies of about 12 options per 20-min session. Technology-aided programs for promoting leisure and communication opportunities might be successfully tailored to persons with spinal cord injury and persons with post-coma multiple disabilities. Implications for Rehabilitation Technology-aided programs may be critical to enable persons with pervasive motor impairment to engage in leisure activities and communication events independently. Persons with spinal cord injury, post-coma extended brain damage, and forms of neurodegenerative disease, such as amyotrophic lateral sclerosis, may benefit from those programs. The programs could be adapted to the participants' characteristics, both in terms of technology and contents, so as to improve their overall impact on the participants' functioning and general mood.

Omega-conotoxin MVIIC attenuates neuronal apoptosis in vitro and improves significant recovery after spinal cord injury in vivo in rats

PubMed Central

Oliveira, Karen M; Lavor, Mário Sérgio L; Silva, Carla Maria O; Fukushima, Fabíola B; Rosado, Isabel R; Silva, Juneo F; Martins, Bernardo C; Guimarães, Laís B; Gomez, Marcus Vinícius; Melo, Marília M; Melo, Eliane G

2014-01-01

Excessive accumulation of intracellular calcium is the most critical step after spinal cord injury (SCI). Reducing the calcium influx should result in a better recovery from SCI. Calcium channel blockers have been shown a great potential in reducing brain and spinal cord injury. In this study, we first tested the neuroprotective effect of MVIIC on slices of spinal cord subjected to ischemia evaluating cell death and caspase-3 activation. Thereafter, we evaluated the efficacy of MVIIC in ameliorating damage following SCI in rats, for the first time in vivo. The spinal cord slices subjected a pretreatment with MVIIC showed a cell protection with a reduction of dead cells in 24.34% and of caspase-3-specific protease activation. In the in vivo experiment, Wistar rats were subjected to extradural compression of the spinal cord at the T12 vertebral level using a weigh of 70 g/cm, following intralesional treatment with either placebo or MVIIC in different doses (15, 30 and 60 pmol) five minutes after injury. Behavioral testing of hindlimb function was done using the Basso Beattie Bresnahan locomotor rating scale, and revealed significant recovery with 15 pmol (G15) compared to other trauma groups. Also, histological bladder structural revealed significant outcome in G15, with no morphological alterations, and anti-NeuN and TUNEL staining showed that G15 provided neuron preservation and indicated that this group had fewer neuron cell death, similar to sham. These results showed the neuroprotective effects of MVIIC in in vitro and in vivo model of SCI with neuronal integrity, bladder and behavioral improvements. PMID:25120731

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 Impact Of Sports Activities On Quality Of Life Of Persons With A Spinal Cord Injury

PubMed Central

Eminović, Fadilj; Dopsaj, Milivoj; Pavlović, Dragan; Arsić, Sladjana; Otašević, Jadranka

2016-01-01

Abstract Objectives Studying the quality of life of people with a spinal cord injury is of great importance as it allows the monitoring of both functioning and adaptation to disability. The aim of this study was to determine the difference between persons with a spinal cord injury involved in sports activities and those not involved in sports activities in relation to their quality of life and the presence of secondary health conditions (pressure ulcers, urinary infections, muscle spasms, osteoporosis, pain, kidney problems-infections, calculosis and poor circulation). Methods The study included a total of 44 participants with spinal cord injury-paraplegia of both genders; 26 of them were athletes and 18 were not athletes. The athletes were training actively for the last two years, minimally 2-3 times per week. A specially designed questionnaire, medical documentation and the Spinal Cord Injury Quality of Life Questionnaire (SCI QL-23) were used for research purposes. Chi-square test was used to analyze the differences between the groups, while multiple analysis of variance (MANOVA) was used to determine the differences between the sets of variables. Results Among the participants, the athletes perceived higher quality of life than the non-athletes (male gender p<0.001 and female gender p<0.05). Regarding secondary health conditions, the athletes reported the presence of less pain (p=0.034) and a subjective feeling of better circulation (p=0.023). Conclusion The implementation of sports activities significantly improves quality of life in the population of people with spinal cord injury-paraplegia. However, sports activities only partially affect secondary health conditions. PMID:27284378

Small GTPase R-Ras participates in neural tube formation in zebrafish embryonic spinal cord.

PubMed

Ohata, Shinya; Uga, Hideko; Okamoto, Hitoshi; Katada, Toshiaki

2018-06-27

Ras related (R-Ras), a small GTPase, is involved in the maintenance of apico-basal polarity in neuroepithelial cells of the zebrafish hindbrain, axonal collapse in cultured murine hippocampal neurons, and maturation of blood vessels in adult mice. However, the role of R-Ras in neural tube formation remains unknown. Using antisense morpholino oligonucleotides (AMOs), we found that in the spinal cord of zebrafish embryos, the lumen was formed bilaterally in rras morphants, whereas it was formed at the midline in control embryos. As AMO can cause off-target effects, we generated rras mutant zebrafish lines using CRISPR/Cas9 technology. Although these rras mutant embryos did not have a bilateral lumen in the spinal cord, the following findings suggest that the phenotype is unlikely due to an off-target effect of rras AMO: 1) The rras morphant phenotype was rescued by an injection of AMO-resistant rras mRNA, and 2) a bilaterally segregated spinal cord was not observed in rras mutant embryos injected with rras AMO. The results suggest that the function of other ras family genes may be redundant in rras mutants. Previous research reported a bilaterally formed lumen in the spinal cord of zebrafish embryos with a mutation in a planar cell polarity (PCP) gene, van gogh-like 2 (vangl2). In the present study, in cultured cells, R-Ras was co-immunoprecipitated with Vangl2 but not with another PCP regulator, Pricke1. Interestingly, the interaction between R-Ras and Vangl2 was stronger in guanine-nucleotide free point mutants of R-Ras than in wild-type or constitutively active (GTP-bound) forms of R-Ras. R-Ras may regulate neural tube formation in cooperation with Vangl2 in the developing zebrafish spinal cord. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Client-centred assessment and the identification of meaningful treatment goals for individuals with a spinal cord injury

PubMed Central

Donnelly, Catherine; Eng, Janice J; Hall, Jill; Alford, Lindsay; Giachino, Rob; Norton, Kathy; Kerr, Debbie Scott

2011-01-01

Study Design Retrospective analysis. Objectives 1) describe the self-care, productivity and leisure problems identified by individuals with a spinal cord injury during rehabilitation, 2) describe the perceived level of satisfaction and performance with self-care, productivity and leisure activities following a spinal cord injury, 3) quantify the relationship between the Canadian Occupational Performance Measure (COPM), a client-centred, individualized measure of function, and the Functional Independence Measure (FIM). Setting Tertiary rehabilitation centre, spinal cord injury unit, GF Strong Rehabilitation Centre, Vancouver, Canada. Methods Health records from 41 individuals with a SCI admitted between 2000 and 2002 were reviewed. Information was obtained from assessments performed on admission and discharge. Self-care, productivity and leisure problems identified by individuals with a SCI were described and their perceived level of performance and satisfaction was calculated. The relationship between the COPM and the FIM was measured by the Pearson product correlation. Results Self-care goals were identified most frequently (79%) followed by productivity (12%) and leisure (9%) goals. The top three problems identified by individuals with a SCI were functional mobility (including transfers and wheelchair use), dressing and grooming. A fair relationship was found between the COPM and the FIM (r between .351 to .514, p<.05) Conclusions The results highlight the importance of including a client-centred outcome measure in the assessment of individual’s with a SCI. Initial support is provided for use of the COPM in individuals with a SCI. PMID:14993893

Living with Spinal Cord Injury

MedlinePlus

... With Spinal Cord Injury A spinal cord injury (SCI) can result from trauma, such as a motor ... these injuries occur in men. A person with SCI typically has some paralysis and decreased or loss ...

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.

Spectrum of Spinal Cord, Spinal Root, and Brain MRI Abnormalities in Congenital Zika Syndrome with and without Arthrogryposis.

PubMed

Aragao, M F V V; Brainer-Lima, A M; Holanda, A C; van der Linden, V; Vasco Aragão, L; Silva Júnior, M L M; Sarteschi, C; Petribu, N C L; Valença, M M

2017-05-01

Arthrogryposis is among the malformations of congenital Zika syndrome. Similar to the brain, there might exist a spectrum of spinal cord abnormalities. The purpose of this study was to explore and describe in detail the MR imaging features found in the spinal cords, nerve roots, and brains of children with congenital Zika syndrome with and without arthrogryposis. Twelve infants with congenital Zika syndrome (4 with arthrogryposis and 8 without) who had undergone brain and spinal cord MR imaging were retrospectively selected. Qualitative and quantitative analyses were performed and compared between groups. At visual inspection, both groups showed reduced thoracic spinal cord thickness: 75% (6/8) of the group without arthrogryposis and 100% (4/4) of the arthrogryposis group. However, the latter had the entire spinal cord reduced and more severely reduced conus medullaris anterior roots (respectively, P = .002 and .007). Quantitative differences were found for conus medullaris base and cervical and lumbar intumescences diameters (respectively, P = .008, .048, .008), with more prominent reduction in arthrogryposis. Periventricular calcifications were more frequent in infants with arthrogryposis ( P = .018). Most infants had some degree of spinal cord thickness reduction, predominant in the thoracic segment (without arthrogryposis) or in the entire spinal cord (with arthrogryposis). The conus medullaris anterior roots were reduced in both groups (thinner in arthrogryposis). A prominent anterior median fissure of the spinal cord was absent in infants without arthrogryposis. Brain stem hypoplasia was present in all infants with arthrogryposis, periventricular calcifications, in the majority, and polymicrogyria was absent. © 2017 by American Journal of Neuroradiology.

The current state-of-the-art of spinal cord imaging: Methods

PubMed Central

Stroman, P.W.; Wheeler-Kingshott, C.; Bacon, M.; Schwab, J.M.; Bosma, R.; Brooks, J.; Cadotte, D.; Carlstedt, T.; Ciccarelli, O.; Cohen-Adad, J.; Curt, A.; Evangelou, N.; Fehlings, M.G.; Filippi, M.; Kelley, B.J.; Kollias, S.; Mackay, A.; Porro, C.A.; Smith, S.; Strittmatter, S.M.; Summers, P.; Tracey, I.

2015-01-01

A first-ever spinal cord imaging meeting was sponsored by the International Spinal Research Trust and the Wings for Life Foundation with the aim of identifying the current state-of-the-art of spinal cord imaging, the current greatest challenges, and greatest needs for future development. This meeting was attended by a small group of invited experts spanning all aspects of spinal cord imaging from basic research to clinical practice. The greatest current challenges for spinal cord imaging were identified as arising from the imaging environment itself; difficult imaging environment created by the bone surrounding the spinal canal, physiological motion of the cord and adjacent tissues, and small cross-sectional dimensions of the spinal cord, exacerbated by metallic implants often present in injured patients. Challenges were also identified as a result of a lack of “critical mass” of researchers taking on the development of spinal cord imaging, affecting both the rate of progress in the field, and the demand for equipment and software to manufacturers to produce the necessary tools. Here we define the current state-of-the-art of spinal cord imaging, discuss the underlying theory and challenges, and present the evidence for the current and potential power of these methods. In two review papers (part I and part II), we propose that the challenges can be overcome with advances in methods, improving availability and effectiveness of methods, and linking existing researchers to create the necessary scientific and clinical network to advance the rate of progress and impact of the research. PMID:23685159

Spinal cord injury - Symptoms and causes

MedlinePlus

... are the leading cause of spinal cord injuries, accounting for almost half of new spinal cord injuries ... address these problems if they affect you. Respiratory system. Your injury may make it more difficult to ...

Spinal cord injury following operative shoulder intervention: A case report.

PubMed

Cleveland, Christine; Walker, Heather

2015-07-01

Cervical myelopathy is a spinal cord dysfunction that results from extrinsic compression of the spinal cord, its blood supply, or both. It is the most common cause of spinal cord dysfunction in patients greater than 55 years of age. A 57-year-old male with right shoulder septic arthritis underwent surgical debridement of his right shoulder and sustained a spinal cord injury intraoperatively. The most likely etiology is damage to the cervical spinal cord during difficult intubation requiring multiple attempts in this patient with underlying asymptomatic severe cervical stenosis. Although it is not feasible to perform imaging studies on all patients undergoing intubation for surgery, this patient's outcome would suggest consideration of inclusion of additional pre-surgical screening examination techniques, such as testing for a positive Hoffman's reflex, is appropriate to detect asymptomatic patients who may have underlying cervical stenosis.

Technical Rebuilding of Movement Function Using Functional Electrical Stimulation

NASA Astrophysics Data System (ADS)

Gföhler, Margit

To rebuild lost movement functions, neuroprostheses based on functional electrical stimulation (FES) artificially activate skeletal muscles in corresponding sequences, using both residual body functions and artificial signals for control. Besides the functional gain, FES training also brings physiological and psychological benefits for spinal cord-injured subjects. In this chapter, current stimulation technology and the main components of FES-based neuroprostheses including enhanced control systems are presented. Technology and application of FES cycling and rowing, both approaches that enable spinal cord-injured subjects to participate in mainstream activities and improve their health and fitness by exercising like able-bodied subjects, are discussed in detail, and an overview of neuroprostheses that aim at restoring movement functions for daily life as walking or grasping is given.

[Homogeneous spinal-shortening axial decompression procedure for tethered cord syndrome].

PubMed

Wang, Haibo; Sun, Jingchuan; Wang, Yuan; Wu, Zhao; Xu, Tao; Chen, Kefu; Shi, Guodong; Yuan, Wen; Jia, Lianshun; Shi, Jiangang

2015-06-16

Surgical detethering is a traditional treatment for symptomatic tethered cord syndrome. However, such complications as cerebrospinal fluid leakage and neurologic deterioration are common. Homogeneous spinal-shortening axial decompression (HSAD) is a modified procedure of monosegmental spinal-shortening osteotomy and it is a novel surgical alternative of reducing neural tension indirectly. The objective was to evaluate the surgical outcomes of HSAD for tethered cord syndrome. The surgical outcomes were examined for 15 consecutive patients with tethered cord syndrome undergoing HSAD from April 2010 to July 2014. Improvements of neurological symptoms including urinary dysfunction, lower-extremity motor and sensory disturbances and/or gait abnormalities, low-back and/or lower-extremity pain, bowel incontinence and sexual dysfunction were evaluated. Their average follow-up period was 21.5 months. The length of spinal column shortening was 17.2 ± 2.9 mm. Urinary dysfunction (n = 9) was the most common residual deficit. All 9 patients with urological symptoms reported improvements, although deficits persisted at the last follow-up. All patients with lower-extremity motor dysfunction improved and 4 (50.0%) noted complete resolution of preoperative lower-extremity sensory symptoms. All patients reported immediate low-back or lower-extremity pain relief after HSAD. One patient reported improved sexual functioning and regained complete erectile capabilities. Two patients (11%) experienced less satisfactory symptomatic or functional benefit from HSAD. However, the main objective of surgery was to prevent further worsening of neurological status. Complete bone union at osteotomy site was noted in all cases at the last follow-up. As a novel surgical option for tethered cord syndrome, HSAD may avoid such complications as cerebrospinal fluid leakage or neurologic deterioration commonly encountered during traditional detethering surgery. All patients gain satisfactory functional outcomes without complications compared to their preoperative symptoms.

21 CFR 882.5850 - Implanted spinal cord stimulator for bladder evacuation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted spinal cord stimulator for bladder evacuation. 882.5850 Section 882.5850 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND....5850 Implanted spinal cord stimulator for bladder evacuation. (a) Identification. An implanted spinal...

21 CFR 882.5850 - Implanted spinal cord stimulator for bladder evacuation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted spinal cord stimulator for bladder evacuation. 882.5850 Section 882.5850 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND....5850 Implanted spinal cord stimulator for bladder evacuation. (a) Identification. An implanted spinal...

International lower urinary tract function basic spinal cord injury data set.

PubMed

Biering-Sørensen, F; Craggs, M; Kennelly, M; Schick, E; Wyndaele, J-J

2008-05-01

To create the International Lower Urinary Tract Function Basic Spinal Cord Injury (SCI) Data Set within the framework of the International SCI Data Sets. International working group. The draft of the Data Set was developed by a working group consisting of the members appointed by the International Continence Society, the European Association of Urology, the American Spinal Injury Association (ASIA), the International Spinal Cord Society (ISCoS) and a representative of the Executive Committee of the International SCI Standards and Data Sets. The final version of the Data Set was developed after review and comments by the members of the Executive Committee of the International SCI Standards and Data Sets, the ISCoS Scientific Committee, ASIA Board, relevant and interested (international) organizations and societies (around 40) and persons, and the ISCoS Council. Endorsement of the Data Set by relevant organizations and societies will be obtained. To make the Data Set uniform, each variable and each response category within each variable have been specifically defined in a way that is designed to promote the collection and reporting of comparable minimal data. Variables included in the International Lower Urinary Tract Function Basic SCI Data Set are as follows: date of data collection, urinary tract impairment unrelated to spinal cord lesion, awareness of the need to empty the bladder, bladder emptying, average number of voluntary bladder emptyings per day during the last week, incontinence within the last 3 months, collecting appliances for urinary incontinence, any drugs for the urinary tract within the last year, surgical procedures on the urinary tract and any change in urinary symptoms within the last year. Complete instruction for data collection, data sheet and training cases available at the website of ISCoS (www.iscos.org.uk) and ASIA (www.asia-spinalinjury.org).

Intensive exercise program after spinal cord injury (“Full-On”): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Rehabilitation after spinal cord injury (SCI) has traditionally involved teaching compensatory strategies for identified impairments and deficits in order to improve functional independence. There is some evidence that regular and intensive activity-based therapies, directed at activation of the paralyzed extremities, promotes neurological improvement. The aim of this study is to compare the effects of a 12-week intensive activity-based therapy program for the whole body with a program of upper body exercise. Methods/Design A multicenter, parallel group, assessor-blinded randomized controlled trial will be conducted. One hundred eighty-eight participants with spinal cord injury, who have completed their primary rehabilitation at least 6 months prior, will be recruited from five SCI units in Australia and New Zealand. Participants will be randomized to an experimental or control group. Experimental participants will receive a 12-week program of intensive exercise for the whole body, including locomotor training, trunk exercises and functional electrical stimulation-assisted cycling. Control participants will receive a 12-week intensive upper body exercise program. The primary outcome is the American Spinal Injuries Association (ASIA) Motor Score. Secondary outcomes include measurements of sensation, function, pain, psychological measures, quality of life and cost effectiveness. All outcomes will be measured at baseline, 12 weeks, 6 months and 12 months by blinded assessors. Recruitment commenced in January 2011. Discussion The results of this trial will determine the effectiveness of a 12-week program of intensive exercise for the whole body in improving neurological recovery after spinal cord injury. Trial registration NCT01236976 (10 November 2010), ACTRN12610000498099 (17 June 2010). PMID:24025260

(18)F-FDG uptake of the spinal cord was decreased after conventional dose radiotherapy in esophageal cancer patients.

PubMed

Harata, Naoki; Yoshida, Katsuya; Oota, Sayako; Fujii, Hayahiko; Isogai, Jun; Yoshimura, Ryoichi

2016-01-01

We retrospectively investigated changes of (18)F-fluorodeocyglucose ((18)F-FDG) uptake in the spinal cord, inside and outside the radiation fields, in patients with esophageal cancer before and after conventional dose radiotherapy. A total of 17 consecutive patients with esophageal cancer (16 males, one female; age 50-83 years, mean 67.0 years), who underwent conventional dose radiotherapy and (18)F-FDG PET/CT before and 5.1 months (range 1.6-8.6 months) after the radiotherapy, were retrospectively evaluated. Sixteen patients had esophageal cancer and one patient had esophageal metastasis from thyroid cancer. Mean standardized uptake values (SUVmean) of the cervical, thoracic (inside and outside the radiation fields) and lumbar spinal cord were measured. SUVmean of the thoracic spinal cord inside the radiation field was decreased significantly after radiotherapy compared to those before radiotherapy (p < 0.001). SUVmean of the cervical spinal cord showed the same trend but it was not statistically significant (p = 0.051). SUVmean of the thoracic spinal cord outside the radiation field and the lumbar spinal cord did not differ significantly before and after the radiotherapy (p = 0.146 and p = 0.701, respectively). The results suggest that glucose metabolism of the spinal cord is decreased in esophageal cancer patients after conventional dose radiotherapy.

Improvements in bladder, bowel and sexual outcomes following task-specific locomotor training in human spinal cord injury.

PubMed

Hubscher, Charles H; Herrity, April N; Williams, Carolyn S; Montgomery, Lynnette R; Willhite, Andrea M; Angeli, Claudia A; Harkema, Susan J

2018-01-01

Locomotor training (LT) as a therapeutic intervention following spinal cord injury (SCI) is an effective rehabilitation strategy for improving motor outcomes, but its impact on non-locomotor functions is unknown. Given recent results of our labs' pre-clinical animal SCI LT studies and existing overlap of lumbosacral spinal circuitries controlling pelvic-visceral and locomotor functions, we addressed whether LT can improve bladder, bowel and sexual function in humans at chronic SCI time-points (> two years post-injury). Prospective cohort study; pilot trial with small sample size. Eight SCI research participants who were undergoing 80 daily one-hour sessions of LT on a treadmill using body-weight support, or one-hour of LT and stand training on alternate days, as part of another research study conducted at the Kentucky Spinal Cord Injury Research Center, University of Louisville, were enrolled in this pilot trial. Urodynamic assessments were performed and International Data Set questionnaire forms completed for bladder, bowel and sexual functions at pre-and post-training time points. Four usual care (non-trained; regular at-home routine) research participants were also enrolled in this study and had the same assessments collected twice, at least 3 months apart. Filling cystometry documented significant increases in bladder capacity, voiding efficiency and detrusor contraction time as well as significant decreases in voiding pressure post-training relative to baseline. Questionnaires revealed a decrease in the frequency of nocturia and urinary incontinence for several research participants as well as a significant decrease in time required for defecation and a significant increase in sexual desire post-training. No significant differences were found for usual care research participants. These results suggest that an appropriate level of sensory information provided to the spinal cord, generated through task-specific stepping and/or loading, can positively benefit the neural circuitries controlling urogenital and bowel functions. ClinicalTrials.gov NCT03036527.

Improvements in bladder, bowel and sexual outcomes following task-specific locomotor training in human spinal cord injury

PubMed Central

Williams, Carolyn S.; Montgomery, Lynnette R.; Willhite, Andrea M.; Angeli, Claudia A.; Harkema, Susan J.

2018-01-01

Objective Locomotor training (LT) as a therapeutic intervention following spinal cord injury (SCI) is an effective rehabilitation strategy for improving motor outcomes, but its impact on non-locomotor functions is unknown. Given recent results of our labs’ pre-clinical animal SCI LT studies and existing overlap of lumbosacral spinal circuitries controlling pelvic-visceral and locomotor functions, we addressed whether LT can improve bladder, bowel and sexual function in humans at chronic SCI time-points (> two years post-injury). Study design Prospective cohort study; pilot trial with small sample size. Methods Eight SCI research participants who were undergoing 80 daily one-hour sessions of LT on a treadmill using body-weight support, or one-hour of LT and stand training on alternate days, as part of another research study conducted at the Kentucky Spinal Cord Injury Research Center, University of Louisville, were enrolled in this pilot trial. Urodynamic assessments were performed and International Data Set questionnaire forms completed for bladder, bowel and sexual functions at pre-and post-training time points. Four usual care (non-trained; regular at-home routine) research participants were also enrolled in this study and had the same assessments collected twice, at least 3 months apart. Results Filling cystometry documented significant increases in bladder capacity, voiding efficiency and detrusor contraction time as well as significant decreases in voiding pressure post-training relative to baseline. Questionnaires revealed a decrease in the frequency of nocturia and urinary incontinence for several research participants as well as a significant decrease in time required for defecation and a significant increase in sexual desire post-training. No significant differences were found for usual care research participants. Conclusions These results suggest that an appropriate level of sensory information provided to the spinal cord, generated through task-specific stepping and/or loading, can positively benefit the neural circuitries controlling urogenital and bowel functions. Trial registration ClinicalTrials.gov NCT03036527 PMID:29385166

Transplantation of spinal cord-derived neural stem cells for ALS: Analysis of phase 1 and 2 trials.

PubMed

Glass, Jonathan D; Hertzberg, Vicki S; Boulis, Nicholas M; Riley, Jonathan; Federici, Thais; Polak, Meraida; Bordeau, Jane; Fournier, Christina; Johe, Karl; Hazel, Tom; Cudkowicz, Merit; Atassi, Nazem; Borges, Lawrence F; Rutkove, Seward B; Duell, Jayna; Patil, Parag G; Goutman, Stephen A; Feldman, Eva L

2016-07-26

To test the safety of spinal cord transplantation of human stem cells in patients with amyotrophic lateral sclerosis (ALS) with escalating doses and expansion of the trial to multiple clinical centers. This open-label trial included 15 participants at 3 academic centers divided into 5 treatment groups receiving increasing doses of stem cells by increasing numbers of cells/injection and increasing numbers of injections. All participants received bilateral injections into the cervical spinal cord (C3-C5). The final group received injections into both the lumbar (L2-L4) and cervical cord through 2 separate surgical procedures. Participants were assessed for adverse events and progression of disease, as measured by the ALS Functional Rating Scale-Revised, forced vital capacity, and quantitative measures of strength. Statistical analysis focused on the slopes of decline of these phase 2 trial participants alone or in combination with the phase 1 participants (previously reported), comparing these groups to 3 separate historical control groups. Adverse events were mostly related to transient pain associated with surgery and to side effects of immunosuppressant medications. There was one incident of acute postoperative deterioration in neurologic function and another incident of a central pain syndrome. We could not discern differences in surgical outcomes between surgeons. Comparisons of the slopes of decline with the 3 separate historical control groups showed no differences in mean rates of progression. Intraspinal transplantation of human spinal cord-derived neural stem cells can be safely accomplished at high doses, including successive lumbar and cervical procedures. The procedure can be expanded safely to multiple surgical centers. This study provides Class IV evidence that for patients with ALS, spinal cord transplantation of human stem cells can be safely accomplished and does not accelerate the progression of the disease. This study lacks the precision to exclude important benefit or safety issues. © 2016 American Academy of Neurology.

Normalization of Blood Pressure With Spinal Cord Epidural Stimulation After Severe Spinal Cord Injury

PubMed Central

Harkema, Susan J.; Wang, Siqi; Angeli, Claudia A.; Chen, Yangsheng; Boakye, Maxwell; Ugiliweneza, Beatrice; Hirsch, Glenn A.

2018-01-01

Chronic low blood pressure and orthostatic hypotension remain challenging clinical issues after severe spinal cord injury (SCI), affecting health, rehabilitation, and quality of life. We previously reported that targeted lumbosacral spinal cord epidural stimulation (scES) could promote stand and step functions and restore voluntary movement in patients with chronic motor complete SCI. This study addresses the effects of targeted scES for cardiovascular function (CV-scES) in individuals with severe SCI who suffer from chronic hypotension. We tested the hypothesis that CV-scES can increase resting blood pressure and attenuate chronic hypotension in individuals with chronic cervical SCI. Four research participants with chronic cervical SCI received an implant of a 16-electrode array on the dura (L1–S1 cord segments, T11–L1 vertebrae). Individual-specific CV-scES configurations (anode and cathode electrode selection, voltage, frequency, and pulse width) were identified to maintain systolic blood pressure within targeted normative ranges without skeletal muscle activity of the lower extremities as assessed by electromyography. These individuals completed five 2-h sessions using CV-scES in an upright, seated position during measurement of blood pressure and heart rate. Noninvasive continuous blood pressure was measured from a finger cuff by plethysmograph technique. For each research participant there were statistically significant increases in mean arterial pressure in response to CV-scES that was maintained within normative ranges. This result was reproducible over the five sessions with concomitant decreases or no changes in heart rate using individual-specific CV-scES that was modulated with modest amplitude changes throughout the session. Our study shows that stimulating dorsal lumbosacral spinal cord can effectively and safely activate mechanisms to elevate blood pressures to normal ranges from a chronic hypotensive state in humans with severe SCI with individual-specific CV-scES. PMID:29568266

Tethered cord release: a long-term study in 114 patients.

PubMed

Bowman, Robin M; Mohan, Avinash; Ito, Joy; Seibly, Jason M; McLone, David G

2009-03-01

All children born with a myelomeningocele at the authors' institution undergo aggressive treatment to maintain or improve functional outcome. Consequently, when any neurological, orthopedic, and/or urological changes are noted, a search for the cause is initiated. The most common cause of decline in a child born with a myelomeningocele is shunt malfunction. The second most common cause is tethering of the distal spinal cord at the site of the original back closure. In this report, the authors review the indicators of symptomatic spinal cord tethering and discuss the surgical interventions and outcomes in the children with myelomeningocele who underwent treatment at Children's Memorial Hospital from 1975 to 2008. Among the 502 children who underwent original closure at Children's Memorial Hospital, a symptomatic tethered spinal cord developed in 114 (23%). Eighty-one patients (71%) have undergone 1 untethering procedure, and 33 patients (29%) have undergone multiple untetherings, for a total of 163 total surgeries. The indicators of symptomatic spinal cord tethering include scoliosis, decline in lower-extremity (LE) motor strength, LE contractures, LE spasticity, gait change, urinary changes, and pain. Pain has shown the best response to surgical untethering, with 100% of children experiencing postoperative improvement. The results of long-term follow-up (average 12 years, range 1 month-23.3 years) in this cohort demonstrated scoliosis progression after surgical untethering in 52% of patients, with 28% requiring spinal fusion. On the 3-month postoperative manual muscle test, 70% of patients showed improved LE muscle strength compared to preoperatively. Gait was also similarly improved after untethering as evaluated by an orthopedic surgeon. Spasticity improved in two-thirds of the cohort, and as expected, LE contractures were stable (78%) postoperatively, as assessed by orthopedic and rehabilitation medicine specialists. Urologically, 64% of patients showed improvements on postoperative bladder evaluation. Although this is a clinical outcome study with no control group, the authors' experience has been that tethered cord release is beneficial in maintaining neurological, urological, and orthopedic functioning in children born with a myelomeningocele.

Associations Between Pre-Implant Psychosocial Factors and Spinal Cord Stimulation Outcome: Evaluation Using the MMPI-2-RF.

PubMed

Block, Andrew R; Marek, Ryan J; Ben-Porath, Yossef S; Kukal, Deborah

2017-01-01

Spinal cord stimulation (SCS) has variable effectiveness in controlling chronic pain. Previous research has demonstrated that psychosocial factors are associated with diminished results of SCS. The objective of this investigation is to examine associations between pre-implant psychological functioning as measured by the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) and SCS outcomes. SCS candidates at two sites (total N = 319) completed the MMPI-2-RF and measures of pain, emotional distress, and functional ability as part of a pre-implant psychological evaluation. At an average of 5 months post-implant, patients completed the measures of pain and emotional distress a second time. Poorer SCS outcomes and poorer patient satisfaction were associated with higher pre-implant MMPI-2-RF scores on scales used to assess emotional dysfunction, somatic/cognitive complaints, and interpersonal problems. Ways through which pre-implant psychological evaluations of spinal cord stimulator candidates can be informed by MMPI-2-RF findings are discussed. © The Author(s) 2015.

Outcome Measures in Spinal Cord Injury

PubMed Central

Alexander, Marcalee S.; Anderson, Kim; Biering-Sorensen, Fin; Blight, Andrew R.; Brannon, Ruth; Bryce, Thomas; Creasey, Graham; Catz, Amiram; Curt, Armin; Donovan, William; Ditunno, John; Ellaway, Peter; Finnerup, Nanna B.; Graves, Daniel E.; Haynes, Beth Ann; Heinemann, Allen W.; Jackson, Amie B.; Johnston, Mark; Kalpakjian, Claire Z.; Kleitman, Naomi; Krassioukov, Andrei; Krogh, Klaus; Lammertse, Daniel; Magasi, Susan; Mulcahey, MJ; Schurch, Brigitte; Sherwood, Arthur; Steeves, John D.; Stiens, Steven; Tulsky, David S.; van Hedel, Hubertus J.A.; Whiteneck, Gale

2009-01-01

Study Design review by the Spinal Cord Outcomes Partnership Endeavor (SCOPE), which is a broad-based international consortium of scientists and clinical researchers representing academic institutions, industry, government agencies, not-for-profit organizations and foundations. Objectives assessment of current and evolving tools for evaluating human spinal cord injury (SCI) outcomes for both clinical diagnosis and clinical research studies. Methods a framework for the appraisal of evidence of metric properties was used to examine outcome tools or tests for accuracy, sensitivity, reliability and validity for human SCI. Results imaging, neurological, functional, autonomic, sexual health, bladder/bowel, pain, and psycho-social tools were evaluated. Several specific tools for human SCI studies have or are being developed to allow the more accurate determination for a clinically meaningful benefit (improvement in functional outcome or quality of life) being achieved as a result of a therapeutic intervention. Conclusion significant progress has been made, but further validation studies are required to identify the most appropriate tools for specific targets in a human SCI study or clinical trial. PMID:19381157

The adaptation to pregnancy of spinal cord injured women.

PubMed

Craig, D I

1990-01-01

This study explored the experiences encountered by spinal cord injured women during pregnancy. The spinal cord injured women experienced complications associated with pregnancy: recurring urinary tract infections, an increase in incontinence, and autonomic dysreflexia. (The first two of these are not unique to spinal cord injury, but are common in all pregnancies.) They neither developed pressure areas nor experienced premature deliveries, major complications predicted by the literature. All felt they were victims of inadequate environmental design that hindered their mobility and inhibited their independence. Many of the psychosocial aspects studied proved to be common to pregnant women in general and not specific to the spinal cord injured population.

Dopamine: a parallel pathway for the modulation of spinal locomotor networks

PubMed Central

Sharples, Simon A.; Koblinger, Kathrin; Humphreys, Jennifer M.; Whelan, Patrick J.

2014-01-01

The spinal cord contains networks of neurons that can produce locomotor patterns. To readily respond to environmental conditions, these networks must be flexible yet at the same time robust. Neuromodulators play a key role in contributing to network flexibility in a variety of invertebrate and vertebrate networks. For example, neuromodulators contribute to altering intrinsic properties and synaptic weights that, in extreme cases, can lead to neurons switching between networks. Here we focus on the role of dopamine in the control of stepping networks in the spinal cord. We first review the role of dopamine in modulating rhythmic activity in the stomatogastric ganglion (STG) and the leech, since work from these preparations provides a foundation to understand its role in vertebrate systems. We then move to a discussion of dopamine’s role in modulation of swimming in aquatic species such as the larval xenopus, lamprey and zebrafish. The control of terrestrial walking in vertebrates by dopamine is less studied and we review current evidence in mammals with a focus on rodent species. We discuss data suggesting that the source of dopamine within the spinal cord is mainly from the A11 area of the diencephalon, and then turn to a discussion of dopamine’s role in modulating walking patterns from both in vivo and in vitro preparations. Similar to the descending serotonergic system, the dopaminergic system may serve as a potential target to promote recovery of locomotor function following spinal cord injury (SCI); evidence suggests that dopaminergic agonists can promote recovery of function following SCI. We discuss pharmacogenetic and optogenetic approaches that could be deployed in SCI and their potential tractability. Throughout the review we draw parallels with both noradrenergic and serotonergic modulatory effects on spinal cord networks. In all likelihood, a complementary monoaminergic enhancement strategy should be deployed following SCI. PMID:24982614

Common neural structures activated by epidural and transcutaneous lumbar spinal cord stimulation: Elicitation of posterior root-muscle reflexes

PubMed Central

Freundl, Brigitta; Binder, Heinrich; Minassian, Karen

2018-01-01

Epidural electrical stimulation of the lumbar spinal cord is currently regaining momentum as a neuromodulation intervention in spinal cord injury (SCI) to modify dysregulated sensorimotor functions and augment residual motor capacity. There is ample evidence that it engages spinal circuits through the electrical stimulation of large-to-medium diameter afferent fibers within lumbar and upper sacral posterior roots. Recent pilot studies suggested that the surface electrode-based method of transcutaneous spinal cord stimulation (SCS) may produce similar neuromodulatory effects as caused by epidural SCS. Neurophysiological and computer modeling studies proposed that this noninvasive technique stimulates posterior-root fibers as well, likely activating similar input structures to the spinal cord as epidural stimulation. Here, we add a yet missing piece of evidence substantiating this assumption. We conducted in-depth analyses and direct comparisons of the electromyographic (EMG) characteristics of short-latency responses in multiple leg muscles to both stimulation techniques derived from ten individuals with SCI each. Post-activation depression of responses evoked by paired pulses applied either epidurally or transcutaneously confirmed the reflex nature of the responses. The muscle responses to both techniques had the same latencies, EMG peak-to-peak amplitudes, and waveforms, except for smaller responses with shorter onset latencies in the triceps surae muscle group and shorter offsets of the responses in the biceps femoris muscle during epidural stimulation. Responses obtained in three subjects tested with both methods at different time points had near-identical waveforms per muscle group as well as same onset latencies. The present results strongly corroborate the activation of common neural input structures to the lumbar spinal cord—predominantly primary afferent fibers within multiple posterior roots—by both techniques and add to unraveling the basic mechanisms underlying electrical SCS. PMID:29381748

Neural pathways for colorectal control, relevance to spinal cord injury and treatment: a narrative review.

PubMed

Callaghan, Brid; Furness, John B; Pustovit, Ruslan V

2018-03-01

Narrative review. The purpose is to review the organisation of the nerve pathways that control defecation and to relate this knowledge to the deficits in colorectal function after SCI. A literature review was conducted to identify salient features of defecation control pathways and the functional consequences of damage to these pathways in SCI. The control pathways for defecation have separate pontine centres under cortical control that influence defecation. The pontine centres connect, separately, with autonomic preganglionic neurons of the spinal defecation centres and somatic motor neurons of Onuf's nucleus in the sacral spinal cord. Organised propulsive motor patterns can be generated by stimulation of the spinal defecation centres. Activation of the somatic neurons contracts the external sphincter. The analysis aids in interpreting the consequences of SCI and predicts therapeutic strategies. Analysis of the bowel control circuits identifies sites at which bowel function may be modulated after SCI. Colokinetic drugs that elicit propulsive contractions of the colorectum may provide valuable augmentation of non-pharmacological bowel management procedures.

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