Sample records for post spinal cord

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

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-12-1-0587 TITLE: Directing Spinal Cord Plasticity: The Impact of Stretch Therapy on Functional Recovery after Spinal Cord...3. DATES COVERED (From - To) 30Sep2014 - 29Sep2015 4. TITLE AND SUBTITLE Directing Spinal Cord Plasticity: The Impact of Stretch Therapy on...ABSTRACT Essentially all spinal cord injured patients receive stretching therapies beginning within the first few weeks post-injury. Despite this fact

  2. Exploring Facilitators of Post-traumatic Growth in Patients with Spinal Cord Injury: A Qualitative Study

    PubMed Central

    Khanjani, Mohammad Saeed; Younesi, Seyed Jalal; Khankeh, Hamid Reza; Azkhosh, Manouchehr

    2017-01-01

    Introduction There is increasing evidence regarding people’s reactions to life stressors in which people also may show positive experiences following a traumatic event. The aim of the present study was to explain the facilitators of post-traumatic growth based on the experiences of patients with a spinal cord injury. Methods This was a qualitative study conducted on 16 Iranian patients with a spinal cord injury using semistructured, in-depth interviews, and content analysis in 2015. These participants, despite their spinal cord injury, were successful in their lives and were considered successful members of society. A purposive sampling method was used until reaching data saturation, and then the collected data were analyzed using a content analysis method. Results The study revealed several factors as facilitators of post-traumatic growth in the patients. The extracted facilitators were put into seven categories of main concepts, including existence of support resources, contact with spinal cord injury associations, spiritual beliefs, positive attitude toward injury, access to proper facilities, enhancement of knowledge and awareness, and active presence in society. Conclusion Different factors may facilitate post-traumatic growth in patients with a spinal cord injury. Understanding these facilitators may help us in designing educational, support, and consulting programs for patients and their families as well as to the correct the support programs. PMID:28243405

  3. Examining the relationship between post-traumatic stress disorder and social participation among Veterans with spinal cord injuries and disorders.

    PubMed

    Etingen, Bella; Locatelli, Sara M; Miskevics, Scott; LaVela, Sherri L

    2017-07-26

    The objectives of this study were to examine differences in social participation among Veterans with spinal cord injuries/disorders with and without post-traumatic stress disorder, and determine if lower social participation was independently associated with having post-traumatic stress disorder. A cross-sectional mailed national survey was sent to a national sample of Veterans with spinal cord injuries/disorders who received prior-year Veterans Affairs healthcare. Surveys provided data on: demographics, health conditions, injury characteristics, and social participation. Analyses included bivariate comparisons, and multivariate logistic regression to determine if lower social participation was independently associated with post-traumatic stress disorder. Veterans with (vs. without) post-traumatic stress disorder (n = 896) reported lower social participation (40.2 vs. 43.9, p < 0.0001). Multivariate analyses showed that longer duration of injury (OR = 0.98, 95% CI: 0.97-1.00, p = 0.04) and white race (OR = 0.62, 95% CI: 0.38-1.01, p = 0.05) were associated with lower odds of post-traumatic stress disorder, while a greater number of health conditions (OR = 1.43, 95% CI: 1.25-1.64, p < 0.0001) was associated with greater odds. When controlling for covariates, lower social participation was independently associated with post-traumatic stress disorder (OR = 0.94, 95% CI: 0.90-0.98, p = 0.003). Results indicate post-traumatic stress disorder is associated with lower social participation in Veterans with spinal cord injuries/disorders, independent of other factors that may impact participation. Efforts to screen for and treat post-traumatic stress disorder among persons with spinal cord injuries/disorders, regardless of injury-specific factors, are needed to improve participation. Implications for Rehabilitation Individuals with spinal cord injuries/disorders often have post-traumatic stress disorder; in Veterans with spinal cord

  4. 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.

  5. 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 ...

  6. 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

  7. 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.

  8. 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

  9. Secondary health conditions in persons with spinal cord injury: a longitudinal study from one to five years post-discharge.

    PubMed

    Adriaansen, Jacinthe J E; Post, Marcel W M; de Groot, Sonja; van Asbeck, Floris W A; Stolwijk-Swüste, Janneke M; Tepper, Marga; Lindeman, Eline

    2013-11-01

    To assess the occurrence of secondary health conditions and their potential risk factors in persons with spinal cord injury from 1 to 5 years after discharge from initial inpatient rehabilitation. Multicentre longitudinal study. A total of 139 wheelchair-dependent persons with spinal cord injury. The occurrence of secondary health conditions and their potential risk factors were assessed in a clinical interview with a rehabilitation physician at 1 and 5 years after discharge from inpatient rehabilitation and by a telephone interview 2 years after discharge. Self-report questionnaires were used for the assessment of musculoskeletal and neuropathic pain. Neuropathic pain (83.7-92.1%), musculoskeletal pain (62.3-87.1%) and urinary tract infection (56.5-58.9%) were the most frequently reported secondary health conditions. The occurrence of several secondary health conditions was higher among women and individuals with a complete lesion, tetraplegia, and with a higher body mass index. Secondary health conditions are common in the first years post-discharge following spinal cord injury, and their course seems to be relatively stable. These results emphasize the number of health issues that must be considered during post-injury care of persons with spinal cord injury living in the community, and the importance of a well-coordinated interdisciplinary approach from specialized rehabilitation centres.

  10. 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.

  11. 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.

  12. Effects of wheelchair propulsion on neuropathic pain and resting electroencephalography after spinal cord injury.

    PubMed

    Sato, Gosuke; Osumi, Michihiro; Morioka, Shu

    2017-01-31

    To investigate the effects of wheelchair propulsion on neuropathic pain and to examine resting electroencephalography pre- and post-wheelchair propulsion after spinal cord injury. Cross-sectional study. Eleven individuals with spinal cord injury and pain and 10 healthy controls. Single-session 15-min wheelchair propulsion and measurement of resting electroence-phalography. Effects of wheelchair propulsion were investigated using numerical rating scale (NRS) for neuropathic pain and short-form Profile of Mood States-Brief for mood. Peak alpha frequency on electroencephalography was calculated in 4 regions of interest; frontal, central, parietal and occipital areas. These outcomes were compared between pre- and post-wheelchair propulsion. Ten participants with spinal cord injury and all healthy controls completed the wheelchair propulsion exercise. NRS scores and negative mood were significantly improved following the wheelchair propulsion exercise. Pre-wheelchair propulsion, parietal and occipital peak alpha frequencies were significantly lower in the spinal cord injury group compared with the healthy controls group. Post-wheelchair propulsion, central peak alpha frequency increased in the spinal cord injury group. Wheelchair propulsion exercise temporarily decreased neuropathic pain intensity, improved negative mood, and modified alpha activity in spinal cord injury.

  13. 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.; hide

    2001-01-01

    The present review presents a series of concepts that may be useful in developing rehabilitative strategies to enhance recovery of posture and locomotion following spinal cord injury. First, the loss of supraspinal input results in a marked change in the functional efficacy of the remaining synapses and neurons of intraspinal and peripheral afferent (dorsal root ganglion) origin. Second, following a complete transection the lumbrosacral spinal cord can recover greater levels of motor performance if it has been exposed to the afferent and intraspinal activation patterns that are associated with standing and stepping. Third, the spinal cord can more readily reacquire the ability to stand and step following spinal cord transection with repetitive exposure to standing and stepping. Fourth, robotic assistive devices can be used to guide the kinematics of the limbs and thus expose the spinal cord to the new normal activity patterns associated with a particular motor task following spinal cord injury. In addition, such robotic assistive devices can provide immediate quantification of the limb kinematics. Fifth, the behavioural and physiological effects of spinal cord transection are reflected in adaptations in most, if not all, neurotransmitter systems in the lumbosacral spinal cord. Evidence is presented that both the GABAergic and glycinergic inhibitory systems are up-regulated following complete spinal cord transection and that step training results in some aspects of these transmitter systems being down-regulated towards control levels. These concepts and observations demonstrate that (a) the spinal cord can interpret complex afferent information and generate the appropriate motor task; and (b) motor ability can be defined to a large degree by training.

  14. Maladaptive spinal plasticity opposes spinal learning and recovery in spinal cord injury

    PubMed Central

    Ferguson, Adam R.; Huie, J. Russell; Crown, Eric D.; Baumbauer, Kyle M.; Hook, Michelle A.; Garraway, Sandra M.; Lee, Kuan H.; Hoy, Kevin C.; Grau, James W.

    2012-01-01

    Synaptic plasticity within the spinal cord has great potential to facilitate recovery of function after spinal cord injury (SCI). Spinal plasticity can be induced in an activity-dependent manner even without input from the brain after complete SCI. A mechanistic basis for these effects is provided by research demonstrating that spinal synapses have many of the same plasticity mechanisms that are known to underlie learning and memory in the brain. In addition, the lumbar spinal cord can sustain several forms of learning and memory, including limb-position training. However, not all spinal plasticity promotes recovery of function. Central sensitization of nociceptive (pain) pathways in the spinal cord may emerge in response to various noxious inputs, demonstrating that plasticity within the spinal cord may contribute to maladaptive pain states. In this review we discuss interactions between adaptive and maladaptive forms of activity-dependent plasticity in the spinal cord below the level of SCI. The literature demonstrates that activity-dependent plasticity within the spinal cord must be carefully tuned to promote adaptive spinal training. Prior work from our group has shown that stimulation that is delivered in a limb position-dependent manner or on a fixed interval can induce adaptive plasticity that promotes future spinal cord learning and reduces nociceptive hyper-reactivity. On the other hand, stimulation that is delivered in an unsynchronized fashion, such as randomized electrical stimulation or peripheral skin injuries, can generate maladaptive spinal plasticity that undermines future spinal cord learning, reduces recovery of locomotor function, and promotes nociceptive hyper-reactivity after SCI. We review these basic phenomena, how these findings relate to the broader spinal plasticity literature, discuss the cellular and molecular mechanisms, and finally discuss implications of these and other findings for improved rehabilitative therapies after SCI. PMID

  15. Secondary damage in the spinal cord after motor cortex injury in rats.

    PubMed

    Weishaupt, Nina; Silasi, Gergely; Colbourne, Frederick; Fouad, Karim

    2010-08-01

    When neurons within the motor cortex are fatally injured, their axons, many of which project into the spinal cord, undergo wallerian degeneration. Pathological processes occurring downstream of the cortical damage have not been extensively studied. We created a focal forelimb motor cortex injury in rats and found that axons from cell bodies located in the hindlimb motor cortex (spared by the cortical injury) become secondarily damaged in the spinal cord. To assess axonal degeneration in the spinal cord, we quantified silver staining in the corticospinal tract (CST) at 1 week and 4 weeks after the injury. We found a significant increase in silver deposition at the thoracic spinal cord level at 4 weeks compared to 1 week post-injury. At both time points, no degenerating neurons could be found in the hindlimb motor cortex. In a separate experiment, we showed that direct injury of neurons within the hindlimb motor cortex caused marked silver deposition in the thoracic CST at 1 week post-injury, and declined thereafter. Therefore, delayed axonal degeneration in the thoracic spinal cord after a focal forelimb motor cortex injury is indicative of secondary damage at the spinal cord level. Furthermore, immunolabeling of spinal cord sections showed that a local inflammatory response dominated by partially activated Iba-1-positive microglia is mounted in the CST, a viable mechanism to cause the observed secondary degeneration of fibers. In conclusion, we demonstrate that following motor cortex injury, wallerian degeneration of axons in the spinal cord leads to secondary damage, which is likely mediated by inflammatory processes.

  16. Interfacing peripheral nerve with macro-sieve electrodes following spinal cord injury.

    PubMed

    Birenbaum, Nathan K; MacEwan, Matthew R; Ray, Wilson Z

    2017-06-01

    Macro-sieve electrodes were implanted in the sciatic nerve of five adult male Lewis rats following spinal cord injury to assess the ability of the macro-sieve electrode to interface regenerated peripheral nerve fibers post-spinal cord injury. Each spinal cord injury was performed via right lateral hemisection of the cord at the T 9-10 site. Five months post-implantation, the ability of the macro-sieve electrode to interface the regenerated nerve was assessed by stimulating through the macro-sieve electrode and recording both electromyography signals and evoked muscle force from distal musculature. Electromyography measurements were recorded from the tibialis anterior and gastrocnemius muscles, while evoked muscle force measurements were recorded from the tibialis anterior, extensor digitorum longus, and gastrocnemius muscles. The macro-sieve electrode and regenerated sciatic nerve were then explanted for histological evaluation. Successful sciatic nerve regeneration across the macro-sieve electrode interface following spinal cord injury was seen in all five animals. Recorded electromyography signals and muscle force recordings obtained through macro-sieve electrode stimulation confirm the ability of the macro-sieve electrode to successfully recruit distal musculature in this injury model. Taken together, these results demonstrate the macro-sieve electrode as a viable interface for peripheral nerve stimulation in the context of spinal cord injury.

  17. Minimally Invasive Drainage of a Post-Laminectomy Subfascial Seroma with Cervical Spinal Cord Compression.

    PubMed

    Kitshoff, Adriaan Mynhardt; Van Goethem, Bart; Cornelis, Ine; Combes, Anais; Dvm, Ingeborgh Polis; Gielen, Ingrid; Vandekerckhove, Peter; de Rooster, Hilde

    2016-01-01

    A 14 mo old female neutered Doberman pinscher was evaluated for difficulty in rising, a wide based stance, pelvic limb gait abnormalities, and cervical pain of 2 mo duration. Neurologic examination revealed pelvic limb ataxia and cervical spinal hyperesthesia. Spinal reflexes and cranial nerve examination were normal. The pathology was localized to the C1-C5 or C6-T2 spinal cord segments. Computed tomography (CT) findings indicated bony proliferation of the caudal articular processes of C6 and the cranial articular processes of C7, resulting in bilateral dorsolateral spinal cord compression that was more pronounced on the left side. A limited dorsal laminectomy was performed at C6-C7. Due to progressive neurological deterioration, follow-up CT examination was performed 4 days postoperatively. At the level of the laminectomy defect, a subfacial seroma had developed, entering the spinal canal and causing significant spinal cord compression. Under ultrasonographic guidance a closed-suction wound catheter was placed. Drainage of the seroma successfully relieved its compressive effects on the spinal cord and the patient's neurological status improved. CT was a valuable tool in assessing spinal cord compression as a result of a postoperative subfascial seroma. Minimally invasive application of a wound catheter can be successfully used to manage this condition.

  18. Cycling exercise and fetal spinal cord transplantation act synergistically on atrophied muscle following chronic spinal cord injury in rats.

    PubMed

    Peterson, C A; Murphy, R J; Dupont-Versteegden, E E; Houlé, J D

    2000-01-01

    The potential of two interventions, alone or in combination, to restore chronic spinal cord transection-induced changes in skeletal muscles of adult Sprague-Dawley rats was studied. Hind limb skeletal muscles were examined in the following groups of animals: rats with a complete spinal cord transection (Tx) for 8 weeks; Tx with a 4-week delay before initiation of a 4-week motor-assisted cycling exercise (Ex) program; Tx with a 4-week delay before transplantation (Tp) of fetal spinal cord tissue into the lesion cavity; Tx with a 4-week delay before Tp and Ex; and uninjured control animals. Muscle mass, muscle to body mass ratios, and mean myofiber cross-sectional areas were significantly reduced 8 weeks after transection. Whereas transplantation of fetal spinal cord tissue did not reverse this atrophy and exercise alone had only a modest effect in restoring lost muscle mass, the combination of exercise and transplantation significantly increased muscle mass, muscle to body mass ratios, and mean myofiber cross-sectional areas in both soleus and plantaris muscles. Spinal cord injury (SCI) also caused changes in myosin heavy chain (MyHC) expression toward faster isoforms in both soleus and plantaris and increased soleus myofiber succinate dehydrogenase (SDH) activity. Combined exercise and transplantation led to a change in the expression of the fastest MyHC isoform in soleus but had no effect in the plantaris. Exercise alone and in combination with transplantation reduced SDH activity to control levels in the soleus. These results suggest a synergistic action of exercise and transplantation of fetal spinal cord tissue on skeletal muscle properties following SCI, even after an extended post-injury period before intervention.

  19. Necrosulfonamide Attenuates Spinal Cord Injury via Necroptosis Inhibition.

    PubMed

    Wang, Yongxiang; Wang, Jingcheng; Wang, Hua; Feng, Xinmin; Tao, Yuping; Yang, Jiandong; Cai, Jun

    2018-06-01

    Spinal cord injury (SCI) is a serious trauma without efficient treatment currently. Necroptosis can be blocked post injury by special inhibitors. This study is to investigate the effects, mechanism, and potential benefit of necrosulfonamide (NSA) for SCI therapy. Pathologic condition was detected using hematoxylin-eosin staining on injured spinal cord and other major organs. Necroptosis-related factors-RIP1, RIP3, and MLKL-were detected using Western blot. Detections on mitochondrial functions such as adenosine triphosphate generation and activities of superoxide dismutase and caspase-3 were also performed. Finally, ethologic performance was detected using a 21-point open-field locomotion test. Reduced lesions and protected neurons were found in the injured spinal cord after treatment with NSA using hematoxylin-eosin staining for pathologic detection. No obvious toxicity on rat liver, kidney, heart, and spleen was detected. Rather than RIP1 and RIP3, MLKL was significantly inhibited by the NSA using Western blot detection. Adenosine triphosphate generation was obviously decreased post injury but slightly increased after the NSA treatment, especially 24 hours post injury. No significant changes were found on activities of superoxide dismutase and caspase-3 after the treatment of NSA. Ethologic performance was significantly improved using a 21-point, open-field locomotion test. Our research indicates NSA attenuates the spinal cord injury via necroptosis inhibition. It might be a potential and safe chemical benefit for SCI therapy. To our knowledge, this is the first study on the effects of NSA as treatment of traumatic SCI. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. 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.

  1. A Brain–Spinal Interface Alleviating Gait Deficits after Spinal Cord Injury in Primates

    PubMed Central

    Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Moraud, Eduardo Martin; Mignardot, Jean-Baptiste; Buse, Nicolas; Gandar, Jerome; Barraud, Quentin; Xing, David; Rey, Elodie; Duis, Simone; Jianzhong, Yang; Ko, Wai Kin D.; Li, Qin; Detemple, Peter; Denison, Tim; Micera, Silvestro; Bezard, Erwan; Bloch, Jocelyne; Courtine, Grégoire

    2016-01-01

    Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain–computer interfaces1–3 have directly linked cortical activity to electrical stimulation of muscles, which have restored grasping abilities after hand paralysis1,4. Theoretically, this strategy could also restore control over leg muscle activity for walking5. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges6,7. Recently, we showed in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion8–10. Here, we interfaced leg motor cortex activity with epidural electrical stimulation protocols to establish a brain–spinal interface that alleviated gait deficits after a spinal cord injury in nonhuman primates. Rhesus monkeys were implanted with an intracortical microelectrode array into the leg area of motor cortex; and a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain–spinal interface in intact monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain–spinal interface restored weight-bearing locomotion of the paralyzed leg on a treadmill and overground. The implantable components integrated in the brain–spinal interface have all been approved for investigational

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

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

    PubMed

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

    2017-01-18

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

  8. [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

  9. 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.

  10. Effects of Enhanced Oxygen Delivery by Perfluorocarbons in Spinal Cord Injury

    DTIC Science & Technology

    2013-10-01

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

  11. 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

  12. 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 ...

  13. 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.

  14. 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.

  15. 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.

  16. Identification of ghost artifact using texture analysis in pediatric spinal cord diffusion tensor images.

    PubMed

    Alizadeh, Mahdi; Conklin, Chris J; Middleton, Devon M; Shah, Pallav; Saksena, Sona; Krisa, Laura; Finsterbusch, Jürgen; Faro, Scott H; Mulcahey, M J; Mohamed, Feroze B

    2018-04-01

    Ghost artifacts are a major contributor to degradation of spinal cord diffusion tensor images. A multi-stage post-processing pipeline was designed, implemented and validated to automatically remove ghost artifacts arising from reduced field of view diffusion tensor imaging (DTI) of the pediatric spinal cord. A total of 12 pediatric subjects including 7 healthy subjects (mean age=11.34years) with no evidence of spinal cord injury or pathology and 5 patients (mean age=10.96years) with cervical spinal cord injury were studied. Ghost/true cords, labeled as region of interests (ROIs), in non-diffusion weighted b0 images were segmented automatically using mathematical morphological processing. Initially, 21 texture features were extracted from each segmented ROI including 5 first-order features based on the histogram of the image (mean, variance, skewness, kurtosis and entropy) and 16s-order feature vector elements, incorporating four statistical measures (contrast, correlation, homogeneity and energy) calculated from co-occurrence matrices in directions of 0°, 45°, 90° and 135°. Next, ten features with a high value of mutual information (MI) relative to the pre-defined target class and within the features were selected as final features which were input to a trained classifier (adaptive neuro-fuzzy interface system) to separate the true cord from the ghost cord. The implemented pipeline was successfully able to separate the ghost artifacts from true cord structures. The results obtained from the classifier showed a sensitivity of 91%, specificity of 79%, and accuracy of 84% in separating the true cord from ghost artifacts. The results show that the proposed method is promising for the automatic detection of ghost cords present in DTI images of the spinal cord. This step is crucial towards development of accurate, automatic DTI spinal cord post processing pipelines. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Spinal cord injury in the emergency context: review of program outcomes of a spinal cord injury rehabilitation program in Sri Lanka

    PubMed Central

    2014-01-01

    Background The final months of the conflict in Sri Lanka in 2009 resulted in massive displacement of the civilian population and a high volume of orthopedic trauma including spinal cord injury. In response to this need, Médecins Sans Frontières implemented a multidisciplinary rehabilitation program. Methods Patients were admitted to the program if they had a spinal cord injury, a stable spine and absence of a high-grade pressure ulcer. All patients were assessed on admission with a standardized functional scale the Spinal Cord Independence Measure II (SCIM) and the American Spinal Injury Association Impairment Scale (ASIA). A multidisciplinary team provided nursing care, physiotherapy, bowel and bladder training, mental health care, and vocational rehabilitation. Patients were discharged from the program when medically stable and able to perform activities of daily living independently or with assistance of a caregiver. The primary outcome measures were discharge to the community, and change in SCIM score on discharge. Secondary outcome measures were measured at 6-12 weeks post-discharge, and included SCIM score and presence of complications (pressure ulcers, urinary tract infections and bowel problems). Results 89 patients were admitted. The majority of injuries were to the thoracic region or higher (89%). The injuries were classified as ASIA grade A in 37 (43%), grade B in 17(20%), grade C in 15 (17%) and grade D in 17(20%). 83.2% met the criteria for discharge, with a further 7.9% patients requiring transfer to hospital for surgical care of pressure ulcers. There was a significant change in SCIM score from 55 on admission to 71 on discharge (p < 0.01). 79.8% and 66.7% achieved a clinically significant and substantially significant SCIM score improvement, respectively. Amongst those with follow up data, there was a reduction in post spinal cord injury complications from those experienced either at or during admission. A further 79% of SCIM scores were

  18. 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.

  19. 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.

  20. Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury

    PubMed Central

    Hou, Shaoping; Carson, David M.; Wu, Di; Klaw, Michelle C.; Houlé, John D.; Tom, Veronica J.

    2016-01-01

    Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH)+ neurons in the autonomic nuclei and superficial dorsal horn in L6–S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH)− and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH+ neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D2-like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH+ neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH+ cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH+ neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI. PMID:26655672

  1. Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury.

    PubMed

    Hou, Shaoping; Carson, David M; Wu, Di; Klaw, Michelle C; Houlé, John D; Tom, Veronica J

    2016-11-01

    Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH) + neurons in the autonomic nuclei and superficial dorsal horn in L6-S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH) - and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH + neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D 2 -like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH + neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH + cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH + neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI. Published by Elsevier Inc.

  2. 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

  3. Spinal Cord Diseases

    MedlinePlus

    ... spinal muscular atrophy Symptoms vary but might include pain, numbness, loss of sensation and muscle weakness. These symptoms can occur around the spinal cord, and also in other areas such as your arms and legs. Treatments often include medicines and surgery.

  4. 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

  5. Optical monitoring of spinal cord subcellular damage after acute spinal cord injury

    NASA Astrophysics Data System (ADS)

    Shadgan, Babak; Manouchehri, Neda; So, Kitty; Shortt, Katelyn; Fong, Allan; Streijger, Femke; Macnab, Andrew; Kwon, Brian K.

    2018-02-01

    Introduction: Sudden physical trauma to the spinal cord results in acute spinal cord injury (SCI), leading to spinal cord (SC) tissue destruction, acute inflammation, increased SC intraparenchymal pressure, and tissue ischemia, hypoxia, and cellular necrosis. The ability to monitor SC tissue viability at subcellular level, using a real-time noninvasive method, would be extremely valuable to clinicians for estimating acute SCI damage, and adjusting and monitoring treatment in the intensive care setting. This study examined the feasibility and sensitivity of a custommade near infrared spectroscopy (NIRS) sensor to monitor the oxidation state of SC mitochondrial cytochrome aa3 (CCO), which reflects the subcellular damage of SC tissue in an animal model of SCI. Methods: Six anesthetized Yorkshire pigs were studied using a custom-made multi-wavelength NIRS system with a miniaturized optical sensor applied directly on the surgically exposed SC at T9. The oxidation states of SC tissue hemoglobin and CCO were monitored before, during and after acute SCI, and during mean arterial pressure alterations. Results: Non-invasive NIRS monitoring reflected changes in SC tissue CCO, simultaneous but independent of changes in hemoglobin saturation following acute SCI. A consistent decrease in SC tissue CCO chromophore concentration (-1.98 +/- 2.1 ab, p<0.05) was observed following SCI, indicating progressive SC cellular damage at the injury site. Elevation of mean arterial pressure can reduce SC tissue damage as suggested by different researchers and observed by significant increase in SC tissue CCO concentration (1.51 +/- 1.7 ab, p<0.05) in this study. Conclusions: This pilot study indicates that a novel miniaturized multi-wave NIRS sensor has the potential to monitor post-SCI changes of SC cytochrome aa3 oxygenation state in real time. Further development of this method may offer new options for improved SCI care.

  6. Malignant spinal cord compression in cancer patients may be mimicked by a primary spinal cord tumour.

    PubMed

    Mohammadianpanah, M; Vasei, M; Mosalaei, A; Omidvari, S; Ahmadloo, N

    2006-12-01

    Although it is quite rare, second primary neoplasms in cancer patients may present with the signs and symptoms of malignant spinal cord compression. Primary spinal cord tumours in the cancer patients may be deceptive and considered as the recurrent first cancer. Therefore, it should be precisely differentiated and appropriately managed. We report such a case of intramedullary ependymoma of the cervical spinal cord mimicking metatstatic recurrent lymphoma and causing cord compression. A 50-year-old man developed intramedullary ependymoma of the cervical spinal cord 1.5 years following chemoradiation for Waldeyer's ring lymphoma. He presented with a 2-month history of neck pain, progressive upper- and lower-extremity numbness and weakness, and bowel and bladder dysfunction. Magnetic resonance imaging revealed an intramedullary expansive lesion extending from C4 to C6 levels of the cervical spinal cord. The clinical and radiological findings were suggestive of malignant process. A comprehensive investigation failed to detect another site of disease. He underwent operation, and the tumour was subtotally resected. The patient's neurological deficits improved subsequently. The development of the intramedullary ependymoma following treating lymphoma has not been reported. We describe the clinical, radiological and pathological findings of this case and review the literature.

  7. Neuroprotective assessment of prolonged local hypothermia post contusive spinal cord injury in rodent model.

    PubMed

    Teh, Daniel Boon Loong; Chua, Soo Min; Prasad, Ankshita; Kakkos, Ioannis; Jiang, Wenxuan; Yue, Mu; Liu, Xiaogang; All, Angelo Homayoun

    2018-03-01

    Although general hypothermia is recognized as a clinically applicable neuroprotective intervention, acute moderate local hypothermia post contusive spinal cord injury (SCI) is being considered a more effective approach. Previously, we have investigated the feasibility and safety of inducing prolonged local hypothermia in the central nervous system of a rodent model. Here, we aimed to verify the efficacy and neuroprotective effects of 5 and 8 hours of local moderate hypothermia (30±0.5°C) induced 2 hours after moderate thoracic contusive SCI in rats. Rats were induced with moderate SCI (12.5 mm) at its T8 section. Local hypothermia (30±0.5°C) was induced 2 hours after injury induction with an M-shaped copper tube with flow of cold water (12°C), from the T6 to the T10 region. Experiment groups were divided into 5-hour and 8-hour hypothermia treatment groups, respectively, whereas the normothermia control group underwent no hypothermia treatment. The neuroprotective effects were assessed through objective weekly somatosensory evoked potential (SSEP) and motor behavior (basso, beattie and bresnahan Basso, Beattie and Bresnahan (BBB) scoring) monitoring. Histology on spinal cord was performed until at the end of day 56. All authors declared no conflict of interest. This work was supported by the Singapore Institute for Neurotechnology Seed Fund (R-175-000-121-733), National University of Singapore, Ministry of Education, Tier 1 (R-172-000-414-112.). Our results show significant SSEP amplitudes recovery in local hypothermia groups starting from day 14 post-injury onward for the 8-hour treatment group, which persisted up to days 28 and 42, whereas the 5-hour group showed significant improvement only at day 42. The functional improvement plateaued after day 42 as compared with control group of SCI with normothermia. This was supported by both 5-hour and 8-hour improvement in locomotion as measured by BBB scores. Local hypothermia also observed insignificant changes

  8. 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 ...

  9. The course of fatigue after acute spinal cord injury.

    PubMed

    Anton, H A; Miller, W C; Townson, A F; Imam, B; Silverberg, N; Forwell, S

    2017-01-01

    Prospective cohort study. To determine the prevalence and course of fatigue following acute spinal cord injury (SCI) during rehabilitation and after discharge. Tertiary spinal cord rehabilitation facility. Fifty-two patients with traumatic SCI were assessed after admission to rehabilitation and followed until 6-months post discharge into the community. Fatigue was measured using the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale for Spinal Cord Injury (MFIS-SCI) at admission, discharge and 6 months after discharge. Clinically significant fatigue was defined as FSS scores ⩾4 or MFIS-SCI scores ⩾24.5. The mean (s.d.) age of our mainly male (78.8%) sample was 46.3 (17.8) years of age. Half had cervical and 61.6% had complete injuries. Mean (s.d.) FSS scores were 3.7 (1.6) at baseline, 3.4 (1.5) at discharge and 3.7 (1.7) post discharge. Mean (s.d.) MFIS-SCI scores were 24.4 (16.1) at baseline, 23.4 (16.3) at discharge and 27.8 (17.5) post discharge. Fatigue on the FSS was present in 51.9% at baseline, 38.3% at discharge and 48.1% post discharge. Fatigue on the MFIS-SCI was present in 44.2% at baseline, 44.7% at discharge and 51.9% post discharge. There was no relationship between fatigue and injury level or completeness. Fatigue is common in SCI patients admitted to rehabilitation. Fatigue remained stable during rehabilitation and after discharge into the community. Clinicians should consider early screening for fatigue and interventions to reduce the consequences of fatigue in people with SCI. The British Columbia Medical Services Foundation funded our study.

  10. 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.

  11. Differences in Affect, Life Satisfaction, and Depression between Successfully and Unsuccessfully Rehabilitated Persons with Spinal Cord Injuries

    ERIC Educational Resources Information Center

    Chapin, Martha H.; Holbert, Donald

    2009-01-01

    This study assessed whether persons with spinal cord injuries who were successfully rehabilitated differed from those who were not with regard to positive and negative affect, life satisfaction, and depression. An ex post facto research design compared persons with spinal cord injuries who were previously employed with persons with spinal cord…

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

    PubMed

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

    2018-05-02

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

  13. 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

  14. Differential expression of ryanodine receptor isoforms after spinal cord injury.

    PubMed

    Pelisch, Nicolas; Gomes, Cynthia; Nally, Jacqueline M; Petruska, Jeffrey C; Stirling, David P

    2017-11-01

    Ryanodine receptors (RyRs) are highly conductive intracellular Ca 2+ release channels and are widely expressed in many tissues, including the central nervous system. RyRs have been implicated in intracellular Ca 2+ overload which can drive secondary damage following traumatic injury to the spinal cord (SCI), but the spatiotemporal expression of the three isoforms of RyRs (RyR1-3) after SCI remains unknown. Here, we analyzed the gene and protein expression of RyR isoforms in the murine lumbar dorsal root ganglion (DRG) and the spinal cord lesion site at 1, 2 and 7 d after a mild contusion SCI. Quantitative RT PCR analysis revealed that RyR3 was significantly increased in lumbar DRGs and at the lesion site at 1 and 2 d post contusion compared to sham (laminectomy only) controls. Additionally, RyR2 expression was increased at 1 d post injury within the lesion site. RyR2 and -3 protein expression was localized to lumbar DRG neurons and their spinal projections within the lesion site acutely after SCI. In contrast, RyR1 expression within the DRG and lesion site remained unaltered following trauma. Our study shows that SCI initiates acute differential expression of RyR isoforms in DRG and spinal cord. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Gene therapy approaches for spinal cord injury

    NASA Astrophysics Data System (ADS)

    Bright, Corinne

    were incorporated in the PEG-PCL-PEG gel and injected into a lesion transecting the main dorsomedial and minor ventral medial corticospinal tract (CST). The degree of collateralization of the transected CST was quantified as an indicator of the regenerative potential of these treatments. At one month post-injury, we observed the robust rostral collateralization of the CST tract in response to the bFGF plasmid-loaded gel. In conclusion, we hope that this platform technology can be applied to the sustained local delivery of other proteins for the treatment of spinal cord injury.

  16. Reduction of microhemorrhages in the spinal cord of symptomatic ALS mice after intravenous human bone marrow stem cell transplantation accompanies repair of the blood-spinal cord barrier.

    PubMed

    Eve, David J; Steiner, George; Mahendrasah, Ajay; Sanberg, Paul R; Kurien, Crupa; Thomson, Avery; Borlongan, Cesar V; Garbuzova-Davis, Svitlana

    2018-02-13

    Blood-spinal cord barrier (BSCB) alterations, including capillary rupture, have been demonstrated in animal models of amyotrophic lateral sclerosis (ALS) and ALS patients. To date, treatment to restore BSCB in ALS is underexplored. Here, we evaluated whether intravenous transplantation of human bone marrow CD34 + (hBM34 + ) cells into symptomatic ALS mice leads to restoration of capillary integrity in the spinal cord as determined by detection of microhemorrhages. Three different doses of hBM34 + cells (5 × 10 4 , 5 × 10 5 or 1 × 10 6 ) or media were intravenously injected into symptomatic G93A SOD1 mice at 13 weeks of age. Microhemorrhages were determined in the cervical and lumbar spinal cords of mice at 4 weeks post-treatment, as revealed by Perls' Prussian blue staining for ferric iron. Numerous microhemorrhages were observed in the gray and white matter of the spinal cords in media-treated mice, with a greater number of capillary ruptures within the ventral horn of both segments. In cell-treated mice, microhemorrhage numbers in the cervical and lumbar spinal cords were inversely related to administered cell doses. In particular, the pervasive microvascular ruptures determined in the spinal cords in late symptomatic ALS mice were significantly decreased by the highest cell dose, suggestive of BSCB repair by grafted hBM34 + cells. The study results provide translational outcomes supporting transplantation of hBM34 + cells at an optimal dose as a potential therapeutic strategy for BSCB repair in ALS patients.

  17. Simultaneous Brain–Cervical Cord fMRI Reveals Intrinsic Spinal Cord Plasticity during Motor Sequence Learning

    PubMed Central

    Cohen-Adad, Julien; Marchand-Pauvert, Veronique; Benali, Habib; Doyon, Julien

    2015-01-01

    The spinal cord participates in the execution of skilled movements by translating high-level cerebral motor representations into musculotopic commands. Yet, the extent to which motor skill acquisition relies on intrinsic spinal cord processes remains unknown. To date, attempts to address this question were limited by difficulties in separating spinal local effects from supraspinal influences through traditional electrophysiological and neuroimaging methods. Here, for the first time, we provide evidence for local learning-induced plasticity in intact human spinal cord through simultaneous functional magnetic resonance imaging of the brain and spinal cord during motor sequence learning. Specifically, we show learning-related modulation of activity in the C6–C8 spinal region, which is independent from that of related supraspinal sensorimotor structures. Moreover, a brain–spinal cord functional connectivity analysis demonstrates that the initial linear relationship between the spinal cord and sensorimotor cortex gradually fades away over the course of motor sequence learning, while the connectivity between spinal activity and cerebellum gains strength. These data suggest that the spinal cord not only constitutes an active functional component of the human motor learning network but also contributes distinctively from the brain to the learning process. The present findings open new avenues for rehabilitation of patients with spinal cord injuries, as they demonstrate that this part of the central nervous system is much more plastic than assumed before. Yet, the neurophysiological mechanisms underlying this intrinsic functional plasticity in the spinal cord warrant further investigations. PMID:26125597

  18. Simultaneous Brain-Cervical Cord fMRI Reveals Intrinsic Spinal Cord Plasticity during Motor Sequence Learning.

    PubMed

    Vahdat, Shahabeddin; Lungu, Ovidiu; Cohen-Adad, Julien; Marchand-Pauvert, Veronique; Benali, Habib; Doyon, Julien

    2015-06-01

    The spinal cord participates in the execution of skilled movements by translating high-level cerebral motor representations into musculotopic commands. Yet, the extent to which motor skill acquisition relies on intrinsic spinal cord processes remains unknown. To date, attempts to address this question were limited by difficulties in separating spinal local effects from supraspinal influences through traditional electrophysiological and neuroimaging methods. Here, for the first time, we provide evidence for local learning-induced plasticity in intact human spinal cord through simultaneous functional magnetic resonance imaging of the brain and spinal cord during motor sequence learning. Specifically, we show learning-related modulation of activity in the C6-C8 spinal region, which is independent from that of related supraspinal sensorimotor structures. Moreover, a brain-spinal cord functional connectivity analysis demonstrates that the initial linear relationship between the spinal cord and sensorimotor cortex gradually fades away over the course of motor sequence learning, while the connectivity between spinal activity and cerebellum gains strength. These data suggest that the spinal cord not only constitutes an active functional component of the human motor learning network but also contributes distinctively from the brain to the learning process. The present findings open new avenues for rehabilitation of patients with spinal cord injuries, as they demonstrate that this part of the central nervous system is much more plastic than assumed before. Yet, the neurophysiological mechanisms underlying this intrinsic functional plasticity in the spinal cord warrant further investigations.

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

    NASA Astrophysics Data System (ADS)

    Li, Nanxi; Li, Ting

    2018-02-01

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

  20. 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.

  1. 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.

  2. 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

  3. Sudden post-traumatic sciatica caused by a thoracic spinal meningioma.

    PubMed

    Mariniello, Giuseppe; Malacario, Francesca; Dones, Flavia; Severino, Rocco; Ugga, Lorenzo; Russo, Camilla; Elefante, Andrea; Maiuri, Francesco

    2016-10-01

    Spinal meningiomas usually present with slowly progressive symptoms of cord and root compression, while a sudden clinical onset is very rare. A 35-year-old previously symptom-free woman presented sudden right sciatica and weakness of her right leg following a fall with impact to her left foot. A neurological examination showed paresis of the right quadriceps, tibial and sural muscles, increased bilateral knee and ankle reflexes and positive Babinski sign. Magnetic resonance imaging (MRI) revealed the presence of a spinal T11 meningioma in the left postero-lateral compartment of the spinal canal; at this level, the spinal cord was displaced to the contralateral side with the conus in the normal position. At surgery, a meningioma with dural attachment of the left postero-lateral dural surface was removed. The intervention resulted in rapid remission of both pain and neurological deficits. Spinal meningiomas may exceptionally present with sudden pain and neurological deficits as result of tumour bleeding or post-traumatic injury of the already compressed nervous structures, both in normal patients and in those with conus displacement or tethered cord. In this case, the traumatic impact of the left foot was transmitted to the spine, resulting in stretching of the already compressed cord and of the contralateral lombosacral roots. This case suggests that low thoracic cord compression should be suspected in patients with post-traumatic radicular leg pain with normal lumbar spine MRI. © The Author(s) 2016.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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).

  9. Pain following Spinal Cord Injury: The Impact on Community Reintegration

    PubMed Central

    Donnelly, Catherine; Eng, Janice J

    2011-01-01

    Study Design Prospective, correlational Objectives 1) describe how pain changes over recovery from admission to spinal cord injury (SCI) rehabilitation, discharge and after 6 months of community living and 2) examine the relationship between pain and community integration at 6 months of community living. Setting Tertiary rehabilitation centre, spinal cord injury unit, Vancouver, Canada. Methods Subjects from 66 consecutive admissions to the Spinal Cord Injury Program of a tertiary rehabilitation centre for the treatment of a traumatic spinal cord injury during the years 2000 to 2002 were followed using data from the National Rehabilitation Reporting System (NRRS). Information was obtained from NRRS standardized assessments performed on admission, discharge and 6 month community living. Early community living was defined as 6-months post-discharge. Community re-integration was assessed by the Reintegration to Normal Living Index (RNL). Pain presence, pain impact and pain intensity were assessed using single item Likhert type scales. Results 86% of individuals with a SCI reported pain at 6-months post discharge, with 27% of these individuals reporting pain that impacted on many or most activities. Pain impact and pain intensity were related to the community re-integration (r=−0.39 and r=−0.55, p<.001), with pain intensity accounting for 25% of the variance in RNL scores. Conclusions Pain is a major consequence of a SCI, impacting on an individual’s activities and perception of how well they are integrated into the community. The results of this study highlight the need to address pain during both the rehabilitation phase of treatment and the early transition into the community. PMID:15570317

  10. [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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. Recovery of locomotion in the cat following spinal cord lesions.

    PubMed

    Rossignol, S; Bouyer, L; Barthélemy, D; Langlet, C; Leblond, H

    2002-10-01

    In most species, locomotor function beneath the level of a spinal cord lesion can be restored even if the cord is completely transected. This suggests that there is, within the spinal cord, an autonomous network of neurons capable of generating a locomotor pattern independently of supraspinal inputs. Recent studies suggest that several physiological and neurochemical changes have to occur in the neuronal networks located caudally to the lesion to allow the expression of spinal locomotion. Some evidence of this plasticity will be addressed in this review. In addition, original data on the functional organisation of the lumbar spinal cord will also be presented. Recent works in our lab show that segmental responsiveness of the spinal cord of the cat to locally micro-injected drugs in different lumbar segments, in combination with complete lesions at various level of the spinal cord, suggest a rostro-caudal organisation of spinal locomotor control. Moreover, the integrity of midlumbar segments seems to be crucial for the expression of spinal locomotion. These data suggest that the regions of critical importance for locomotion can be confined to a restricted portion of the spinal cord. Later, these midlumbar segments could be targeted by electrical stimulation or grafts to improve recovery of function. Understanding the changes in spinal cord neurophysiology and neurochemistry after a lesion is of critical importance to the improvement of treatments for locomotor rehabilitation in spinal-cord-injured patients.

  19. Acute electroacupuncture inhibits nitric oxide synthase expression in the spinal cord of neuropathic rats.

    PubMed

    Cha, Myeoung Hoon; Bai, Sun Joon; Lee, Kyung Hee; Cho, Zang Hee; Kim, Young-Bo; Lee, Hye-Jung; Lee, Bae Hwan

    2010-02-01

    To examine the effects of electroacupuncture stimulation on behavioral changes and neuronal nitric oxide synthase expression in the rat spinal cord after nerve injury. Under pentobarbital anesthesia, male Sprague-Dawley rats were subjected to neuropathic surgery by tightly ligating and cutting the left tibial and sural nerves. Behavioral responses to mechanical stimulation were tested for 2 weeks post-operatively. At the end of behavioral testing, electroacupuncture stimulation was applied to ST36 (Choksamni) and SP9 (Eumleungcheon) acupoints. Immunocytochemical staining was performed to investigate changes in the expression of neuronal nitric oxide synthase-immunoreactive neurons in the L4-5 spinal cord. Mechanical allodynia was observed by nerve injury. The mechanical allodynia was decreased after electroacupuncture stimulation. Neuronal nitric oxide synthase expression was also decreased in L4-5 spinal cord by electroacupuncture treatment. These results suggest that electroacupuncture relieves mechanical allodynia in the neuropathic rats possibly by the inhibition of neuronal nitric oxide synthase expression in the spinal cord.

  20. Microsurgical resection of intramedullary spinal cord hemangioblastoma.

    PubMed

    McCormick, Paul C

    2014-09-01

    Spinal cord hemangioblastomas account for about 10% of spinal cord tumors. They usually arise from the dorsolateral pia mater and are characterized by their significant vascularity. The principles and techniques of safe resection are different than those employed for the more commonly occurring intramedullary glial tumors (e.g. ependymoma, astrocytoma) and consist of circumferential detachment of the tumor margin from the surrounding normal pia. This video demonstrates the microsurgical techniques of resection of a thoracic spinal cord hemangioblastoma. The video can be found here: http://youtu.be/yT5KLi4VyAo.

  1. Regenerative Potential of Ependymal Cells for Spinal Cord Injuries Over Time.

    PubMed

    Li, Xiaofei; Floriddia, Elisa M; Toskas, Konstantinos; Fernandes, Karl J L; Guérout, Nicolas; Barnabé-Heider, Fanie

    2016-11-01

    Stem cells have a high therapeutic potential for the treatment of spinal cord injury (SCI). We have shown previously that endogenous stem cell potential is confined to ependymal cells in the adult spinal cord which could be targeted for non-invasive SCI therapy. However, ependymal cells are an understudied cell population. Taking advantage of transgenic lines, we characterize the appearance and potential of ependymal cells during development. We show that spinal cord stem cell potential in vitro is contained within these cells by birth. Moreover, juvenile cultures generate more neurospheres and more oligodendrocytes than adult ones. Interestingly, juvenile ependymal cells in vivo contribute to glial scar formation after severe but not mild SCI, due to a more effective sealing of the lesion by other glial cells. This study highlights the importance of the age-dependent potential of stem cells and post-SCI environment in order to utilize ependymal cell's regenerative potential. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Revisiting the segmental organization of the human spinal cord.

    PubMed

    Leijnse, J N; D'Herde, K

    2016-09-01

    In classic anatomic atlases, the spinal cord is standardly represented in its anatomical form with symmetrically emerging anterior and posterior roots, which at the level of the intervertebral foramen combine into the spinal nerves. The parts of the cord delimited by the boundaries of the roots are called segments or myelomeres. Associated with their regular repetitive appearance is the notion that the cord is segmentally organized. This segmental view is reinforced by clinical practice. Spinal cord roots innervate specific body parts. The level of cord trauma is diagnosed by the de-innervation symptoms of these parts. However, systemically, the case for a segmentally organized cord is not so clear. To date, developmental and genetic research points to a regionally rather than a segmentally organized cord. In the present study, to what degree the fila radicularia are segmentally implanted along the cord was investigated. The research hypothesis was that if the fila radicularia were non-segmentally implanted at the cord surface, it would be unlikely that the internal neuron stratum would be segmented. The visual segmented aspect of the myelomeres would then be the consequence of the necessary bundling of axons towards the vertebral foramen as the only exits of the vertebral canal, rather than of an underlying segment organization of the cord itself. To investigate the research hypothesis, the fila radicularia in the cervical-upper thoracic part of five spinal cords were detached from their spinal nerves and dissected in detail. The principal research question was if the fila radicularia are separated from their spinal nerves and dissected from their connective tissues up to the cord, would it be possible to reconstruct the original spinal segments from the morphology and interspaces of the fila? The dissections revealed that the anterior fila radicularia emerge from the cord at regular regionally modulated interspaces without systematic segmental delineations. The

  3. Spinal cord tumors: new views and future directions.

    PubMed

    Mechtler, Laszlo L; Nandigam, Kaveer

    2013-02-01

    Spinal cord tumors are uncommon neoplasms that, without treatment, can cause significant neurologic morbidity and mortality. The historic classification of spine tumors is based on the use of myelography with 3 main groups: (1) extramedullary extradural, (2) intradural extramedullary, and (3) intradural intramedullary. This chapter focuses on intramedullary spinal cord tumors (ISCTs), with an emphasis on new diagnostic imaging modalities and treatment options. The common ISCTs include ependymoma, astrocytoma and hemangioblastoma, which together account for over 90% of primary ISCTs. Rare tumors such as gangliglioma, oligodendroglioma, paraganglioma, melanocytoma, lipoma, and primary spinal cord lymphoma are also included in this review, in addition to spinal cord metastatic disease. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. 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.

  5. 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.

  6. 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...

  7. 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.

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

    DTIC Science & Technology

    2014-10-01

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

  9. Spinal cord aspergillus invasion--complication of an aspergilloma.

    PubMed

    Sheth, N K; Varkey, B; Wagner, D K

    1985-12-01

    Acute paraplegia developed in a 53-year-old man with pulmonary aspergilloma because of contiguous extension of Aspergillus infection to the epidural and subdural spaces and spinal cord. Histopathologic findings of the spinal cord showed Aspergillus hyphae penetrating the myelin sheath and myelomalacia, predominantly in the anterior and lateral columns. To the authors' knowledge, there have been no previous descriptions or illustrations of spinal cord involvement and the pathologic changes caused by Aspergillus infection.

  10. Idiopathic thoracic transdural intravertebral spinal cord herniation

    PubMed Central

    Turel, Mazda K; Wewel, Joshua T; Kerolus, Mena G; O'Toole, John E

    2017-01-01

    Idiopathic spinal cord herniation is a rare and often missed cause of thoracic myelopathy. The clinical presentation and radiological appearance is inconsistent and commonly confused with a dorsal arachnoid cyst and often is a misdiagnosed entity. While ventral spinal cord herniation through a dural defect has been previously described, intravertebral herniation is a distinct entity and extremely rare. We present the case of a 70-year old man with idiopathic thoracic transdural intravertebral spinal cord herniation and discuss the clinico-radiological presentation, pathophysiology and operative management along with a review the literature of this unusual entity. PMID:29021685

  11. Spinal Meninges and Their Role in Spinal Cord Injury: A Neuroanatomical Review.

    PubMed

    Grassner, Lukas; Grillhösl, Andreas; Griessenauer, Christoph J; Thomé, Claudius; Bühren, Volker; Strowitzki, Martin; Winkler, Peter A

    2018-02-01

    Current recommendations support early surgical decompression and blood pressure augmentation after traumatic spinal cord injury (SCI). Elevated intraspinal pressure (ISP), however, has probably been underestimated in the pathophysiology of SCI. Recent studies provide some evidence that ISP measurements and durotomy may be beneficial for individuals suffering from SCI. Compression of the spinal cord against the meninges in SCI patients causes a "compartment-like" syndrome. In such cases, intentional durotomy with augmentative duroplasty to reduce ISP and improve spinal cord perfusion pressure (SCPP) may be indicated. Prior to performing these procedures routinely, profound knowledge of the spinal meninges is essential. Here, we provide an in-depth review of relevant literature along with neuroanatomical illustrations and imaging correlates.

  12. 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) ...

  13. [Subcutaneous stimulation as additional therapy to spinal cord stimulation in a post-laminectomy syndrome patient].

    PubMed

    Akbaş, Mert; Yeğin, Mehmet Arif; Özdemir, İrem; Göksu, Ethem; Akyüz, Mahmut

    2016-01-01

    Spinal cord stimulation as treatment of chronic low back pain via neuromodulation has been frequently performed in recent years. The dorsal column is stimulated by an electrode placed at the epidural region. In the case presently described, subcutaneous lead was implanted in a patient with failed back syndrome after spinal cord stimulation was inadequate to treat back and gluteal pain. A 65-year-old male had undergone surgery to treat lumbar disc herniation, after which he received physical therapy and multiple steroid injections due to unrelieved pain. He was admitted to the pain clinic with pain radiating to right gluteal muscle and leg. Spinal cord stimulation was performed and, as pain was not relieved, subcutaneous lead was applied to the right cluneal nerve distribution. Following treatment, the patient scored 1-2 on visual analog scale. Pain had been reduced by over 80%. Octad electrode was placed between T8 and T10 vertebrae after Tuohy needle was introduced to intervertebral area between L1 and L2. Paresthesia occurred in the right extremity. Boundaries were determined by area of right gluteal region in which paresthesia did not occur. Octad electrode was placed subcutaneously after vertical line was drawn from center point. Paresthesia occurred throughout the region. Pulse wave was 390-450 msec; frequency was 10-30 Hz. Subcutaneous electrode replacement is effective additional therapy when pain is not relieved by spinal cord stimulation.

  14. Spinal cord trauma

    MedlinePlus

    ... Oh's Intensive Care Manual . 7th ed. Philadelphia, PA: Elsevier; 2014:chap 78. Bryce TN. Spinal cord injury. ... Physical Medicine and Rehabilitation . 5th ed. Philadelphia, PA: Elsevier; 2016:chap 49. Dalzell K, Nouri A, Fehlings ...

  15. Blood-Spinal Cord Barrier Alterations in Subacute and Chronic Stages of a Rat Model of Focal Cerebral Ischemia

    PubMed Central

    Haller, Edward; Tajiri, Naoki; Thomson, Avery; Barretta, Jennifer; Williams, Stephanie N.; Haim, Eithan D.; Qin, Hua; Frisina-Deyo, Aric; Abraham, Jerry V.; Sanberg, Paul R.; Van Loveren, Harry; Borlongan, Cesario V.

    2016-01-01

    We previously demonstrated blood-brain barrier impairment in remote contralateral brain areas in rats at 7 and 30 days after transient middle cerebral artery occlusion (tMCAO), indicating ischemic diaschisis. Here, we focused on effects of subacute and chronic focal cerebral ischemia on the blood-spinal cord barrier (BSCB). We observed BSCB damage on both sides of the cervical spinal cord in rats at 7 and 30 days post-tMCAO. Major BSCB ultrastructural changes in spinal cord gray and white matter included vacuolated endothelial cells containing autophagosomes, pericyte degeneration with enlarged mitochondria, astrocyte end-feet degeneration and perivascular edema; damaged motor neurons, swollen axons with unraveled myelin in ascending and descending tracts and astrogliosis were also observed. Evans Blue dye extravasation was maximal at 7 days. There was immunofluorescence evidence of reduction of microvascular expression of tight junction occludin, upregulation of Beclin-1 and LC3B immunoreactivities at 7 days and a reduction of the latter at 30 days post-ischemia. These novel pathological alterations on the cervical spinal cord microvasculature in rats after tMCAO suggest pervasive and long-lasting BSCB damage after focal cerebral ischemia, and that spinal cord ischemic diaschisis should be considered in the pathophysiology and therapeutic approaches in patients with ischemic cerebral infarction. PMID:27283328

  16. 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

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

    PubMed

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

    2018-06-01

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

  18. 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.

  19. 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

  20. Axonal loss in the multiple sclerosis spinal cord revisited.

    PubMed

    Petrova, Natalia; Carassiti, Daniele; Altmann, Daniel R; Baker, David; Schmierer, Klaus

    2018-05-01

    Preventing chronic disease deterioration is an unmet need in people with multiple sclerosis, where axonal loss is considered a key substrate of disability. Clinically, chronic multiple sclerosis often presents as progressive myelopathy. Spinal cord cross-sectional area (CSA) assessed using MRI predicts increasing disability and has, by inference, been proposed as an indirect index of axonal degeneration. However, the association between CSA and axonal loss, and their correlation with demyelination, have never been systematically investigated using human post mortem tissue. We extensively sampled spinal cords of seven women and six men with multiple sclerosis (mean disease duration= 29 years) and five healthy controls to quantify axonal density and its association with demyelination and CSA. 396 tissue blocks were embedded in paraffin and immuno-stained for myelin basic protein and phosphorylated neurofilaments. Measurements included total CSA, areas of (i) lateral cortico-spinal tracts, (ii) gray matter, (iii) white matter, (iv) demyelination, and the number of axons within the lateral cortico-spinal tracts. Linear mixed models were used to analyze relationships. In multiple sclerosis CSA reduction at cervical, thoracic and lumbar levels ranged between 19 and 24% with white (19-24%) and gray (17-21%) matter atrophy contributing equally across levels. Axonal density in multiple sclerosis was lower by 57-62% across all levels and affected all fibers regardless of diameter. Demyelination affected 24-48% of the gray matter, most extensively at the thoracic level, and 11-13% of the white matter, with no significant differences across levels. Disease duration was associated with reduced axonal density, however not with any area index. Significant association was detected between focal demyelination and decreased axonal density. In conclusion, over nearly 30 years multiple sclerosis reduces axonal density by 60% throughout the spinal cord. Spinal cord cross sectional area

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

    DTIC Science & Technology

    2013-10-01

    2   INTRODUCTION: The magnitude of acute post- traumatic hemorrhagic necrosis (PHN) is an early prognostic indicator of long-term...Efficacy of Glibenclamide in Limiting Progressive Hemorrhagic Necrosis Following Traumatic Spinal Cord Injury PRINCIPAL INVESTIGATOR: J. Marc Simard...Limiting Progressive Hemorrhagic Necrosis Following Traumatic Spinal Cord Injury 5b. GRANT NUMBER W81XWH-10-1-0898 5c. PROGRAM ELEMENT NUMBER 6

  2. 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

  3. Enrichment of spinal cord cell cultures with motoneurons

    PubMed Central

    1978-01-01

    Spinal cord cell cultures contain several types of neurons. Two methods are described for enriching such cultures with motoneurons (defined here simply as cholinergic cells that are capable of innervating muscle). In the first method, 7-day embryonic chick spinal cord neurons were separated according to size by 1 g velocity sedimentation. It is assumed that cholinergic motoneurons are among the largest cells present at this stage. The spinal cords were dissociated vigorously so that 95-98% of the cells in the initial suspension were isolated from one another. Cells in leading fractions (large cell fractions: LCFs) contain about seven times as much choline acetyltransferase (CAT) activity per unit cytoplasm as do cells in trailing fractions (small cell fractions: SCFs). Muscle cultures seeded with LCFs develop 10-70 times as much CAT as cultures seeded with SCFs and six times as much CAT as cultures seeded with control (unfractionated) spinal cord cells. More than 20% of the large neurons in LCF-muscle cultures innervate nearby myotubes. In the second method, neurons were gently dissociated from 4-day embryonic spinal cords and maintained in vitro. This approach is based on earlier observations that cholinergic neurons are among the first cells to withdraw form the mitotic cycle in the developing chick embryo (Hamburger, V. 1948. J. Comp. Neurol. 88:221- 283; and Levi-Montalcini, R. 1950. J. Morphol. 86:253-283). 4-Day spinal cord-muscle cultures develop three times as much CAT as do 7-day spinal cord-muscle plates, prepared in the same (gentle) manner. More than 50% of the relatively large 4-day neurons innervate nearby myotubes. Thus, both methods are useful first steps toward the complete isolation of motoneurons. Both methods should facilitate study of the development of cholinergic neurons and of nerve-muscle synapse formation. PMID:566275

  4. Spinal cord injury below-level neuropathic pain relief with dorsal root entry zone microcoagulation performed caudal to level of complete spinal cord transection.

    PubMed

    Falci, Scott; Indeck, Charlotte; Barnkow, Dave

    2018-06-01

    OBJECTIVE Surgically created lesions of the spinal cord dorsal root entry zone (DREZ) to relieve central pain after spinal cord injury (SCI) have historically been performed at and cephalad to, but not below, the level of SCI. This study was initiated to investigate the validity of 3 proposed concepts regarding the DREZ in SCI central pain: 1) The spinal cord DREZ caudal to the level of SCI can be a primary generator of SCI below-level central pain. 2) Neuronal transmission from a DREZ that generates SCI below-level central pain to brain pain centers can be primarily through sympathetic nervous system (SNS) pathways. 3) Perceived SCI below-level central pain follows a unique somatotopic map of DREZ pain-generators. METHODS Three unique patients with both intractable SCI below-level central pain and complete spinal cord transection at the level of SCI were identified. All 3 patients had previously undergone surgical intervention to their spinal cords-only cephalad to the level of spinal cord transection-with either DREZ microcoagulation or cyst shunting, in failed attempts to relieve their SCI below-level central pain. Subsequent to these surgeries, DREZ lesioning of the spinal cord solely caudal to the level of complete spinal cord transection was performed using electrical intramedullary guidance. The follow-up period ranged from 1 1/2 to 11 years. RESULTS All 3 patients in this study had complete or near-complete relief of all below-level neuropathic pain. The analyzed electrical data confirmed and enhanced a previously proposed somatotopic map of SCI below-level DREZ pain generators. CONCLUSIONS The results of this study support the following hypotheses. 1) The spinal cord DREZ caudal to the level of SCI can be a primary generator of SCI below-level central pain. 2) Neuronal transmission from a DREZ that generates SCI below-level central pain to brain pain centers can be primarily through SNS pathways. 3) Perceived SCI below-level central pain follows a unique

  5. '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.

  6. 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.

  7. Early Versus Delayed Surgical Decompression of Spinal Cord after Traumatic Cervical Spinal Cord Injury: A Cost-Utility Analysis.

    PubMed

    Furlan, Julio C; Craven, B Catharine; Massicotte, Eric M; Fehlings, Michael G

    2016-04-01

    This cost-utility analysis was undertaken to compare early (≤24 hours since trauma) versus delayed surgical decompression of spinal cord to determine which approach is more cost effective in the management of patients with acute traumatic cervical spinal cord injury (SCI). This study includes the patients enrolled into the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS) and admitted at Toronto Western Hospital. Cases were grouped into patients with motor complete SCI and individuals with motor incomplete SCI. A cost-utility analysis was performed for each group of patients by the use of data for the first 6 months after SCI. The perspective of a public health care insurer was adopted. Costs were estimated in 2014 U.S. dollars. Utilities were estimated from the STASCIS. The baseline analysis indicates early spinal decompression is more cost-effective approach compared with the delayed spinal decompression. When we considered the delayed spinal decompression as the baseline strategy, the incremental cost-effectiveness ratio analysis revealed a saving of US$ 58,368,024.12 per quality-adjusted life years gained for patients with complete SCI and a saving of US$ 536,217.33 per quality-adjusted life years gained in patients with incomplete SCI for the early spinal decompression. The probabilistic analysis confirmed the early-decompression strategy as more cost effective than the delayed-decompression approach, even though there is no clearly dominant strategy. The results of this economic analysis suggests that early decompression of spinal cord was more cost effective than delayed surgical decompression in the management of patients with motor complete and incomplete SCI, even though no strategy was clearly dominant. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. Propitious Therapeutic Modulators to Prevent Blood-Spinal Cord Barrier Disruption in Spinal Cord Injury.

    PubMed

    Kumar, Hemant; Ropper, Alexander E; Lee, Soo-Hong; Han, Inbo

    2017-07-01

    The blood-spinal cord barrier (BSCB) is a specialized protective barrier that regulates the movement of molecules between blood vessels and the spinal cord parenchyma. Analogous to the blood-brain barrier (BBB), the BSCB plays a crucial role in maintaining the homeostasis and internal environmental stability of the central nervous system (CNS). After spinal cord injury (SCI), BSCB disruption leads to inflammatory cell invasion such as neutrophils and macrophages, contributing to permanent neurological disability. In this review, we focus on the major proteins mediating the BSCB disruption or BSCB repair after SCI. This review is composed of three parts. Section 1. SCI and the BSCB of the review describes critical events involved in the pathophysiology of SCI and their correlation with BSCB integrity/disruption. Section 2. Major proteins involved in BSCB disruption in SCI focuses on the actions of matrix metalloproteinases (MMPs), tumor necrosis factor alpha (TNF-α), heme oxygenase-1 (HO-1), angiopoietins (Angs), bradykinin, nitric oxide (NO), and endothelins (ETs) in BSCB disruption and repair. Section 3. Therapeutic approaches discusses the major therapeutic compounds utilized to date for the prevention of BSCB disruption in animal model of SCI through modulation of several proteins.

  14. 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

  15. Does the intrathecal propofol have a neuroprotective effect on spinal cord ischemia?

    PubMed

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

    2015-11-01

    The neuroprotective effects of propofol have been confirmed. However, it remains unclear whether intrathecal administration of propofol exhibits neuroprotective effects on spinal cord ischemia. At 1 hour prior to spinal cord ischemia, propofol (100 and 300 µg) was intrathecally administered in rats with spinal cord ischemia. Propofol pre-treatment greatly improved rat pathological changes and neurological function deficits at 24 hours after spinal cord ischemia. These results suggest that intrathecal administration of propofol exhibits neuroprotective effects on spinal cord structural and functional damage caused by ischemia.

  16. [Spinal cord injury due to penetrating missiles].

    PubMed

    Ohry, Avi

    2003-10-01

    Gunshot wound of the spine is a major cause of spinal cord injury among US civilian population, members of the military armed conflict personnel, or civilians injured in terrorists attacks. The bullet fragments cause damage to the spinal cord even without penetrating the spinal canal. Concussive effects, heat, fractures or vascular injury may cause the neurological damage. Unfortunately, bullet or shrapnel removal or laminectomy do not change the prognosis. In this article we review the historical background, the Israeli experience, ballistic-forensic considerations, complications, treatment and prognosis.

  17. Observational study of the effectiveness of spinal cord injury rehabilitation using the Spinal Cord Injury-Ability Realization Measurement Index.

    PubMed

    Scivoletto, G; Bonavita, J; Torre, M; Baroncini, I; Tiberti, S; Maietti, E; Laurenza, L; China, S; Corallo, V; Guerra, F; Buscaroli, L; Candeloro, C; Brunelli, E; Catz, A; Molinari, M

    2016-06-01

    Retrospective observational study. The objective of this study was to determine the rehabilitation potential and the extent to which it is realized in a cohort of spinal cord injury patients using the Spinal Cord Injury-Ability Realization Measurement Index (SCI-ARMI) and to study the clinical factors that influence this realization. Two spinal units in Italy. Consecutive patients were assessed at the end of an in-patient rehabilitation program using the Spinal Cord Independence Measure and the International Standards for Neurological Classification of Spinal Cord Injury. On the basis of these data and of the age and gender of the patients, we calculated the SCI-ARMI score. Regression analyses were performed to study the relationship between clinical factors and the extent to which rehabilitation potential is realized. We examined the data for 306 patients. Most patients were discharged without having reached their rehabilitation potential, with an SCI-ARMI score <80%. SCI-ARMI scores at discharge were positively influenced by etiology and the lesion level and correlated negatively with lesion severity and the presence of complications during rehabilitation. The SCI-ARMI is an effective tool that can be used to measure the achievement of rehabilitation potential in SCI patients and to identify groups of patients who are at risk of not meeting their rehabilitative potential.

  18. 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.

  19. 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

  20. 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.

  1. Neuroprotection and Acute Spinal Cord Injury: A Reappraisal

    PubMed Central

    Hall, Edward D.; Springer, Joe E.

    2004-01-01

    Summary: It has long been recognized that much of the post-traumatic degeneration of the spinal cord following injury is caused by a multi-factorial secondary injury process that occurs during the first minutes, hours, and days after spinal cord injury (SCI). A key biochemical event in that process is reactive oxygen-induced lipid peroxidation (LP). In 1990 the results of the Second National Acute Spinal Cord Injury Study (NASCIS II) were published, which showed that the administration of a high-dose regimen of the glucocorticoid steroid methylprednisolone (MP), which had been previously shown to inhibit post-traumatic LP in animal models of SCI, could improve neurological recovery in spinal-cord-injured humans. This resulted in the registration of high-dose MP for acute SCI in several countries, although not in the U.S. Nevertheless, this treatment quickly became the standard of care for acute SCI since the drug was already on the U.S. market for many other indications. Subsequently, it was demonstrated that the non-glucocorticoid 21-aminosteroid tirilazad could duplicate the antioxidant neuroprotective efficacy of MP in SCI models, and evidence of human efficacy was obtained in a third NASCIS trial (NASCIS III). In recent years, the use of high-dose MP in acute SCI has become controversial largely on the basis of the risk of serious adverse effects versus what is perceived to be on average a modest neurological benefit. The opiate receptor antagonist naloxone was also tested in NASCIS II based upon the demonstration of its beneficial effects in SCI models. Although it did not a significant overall effect, some evidence of efficacy was seen in incomplete (i.e., paretic) patients. The monosialoganglioside GM1 has also been examined in a recently completed clinical trial in which the patients first received high-dose MP treatment. However, GM1 failed to show any evidence of a significant enhancement in the extent of neurological recovery over the level afforded by

  2. 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.

  3. Protective effect of melatonin on experimental spinal cord ischemia.

    PubMed

    Erten, S F; Kocak, A; Ozdemir, I; Aydemir, S; Colak, A; Reeder, B S

    2003-10-01

    Experimental animal model to assess ischemic spinal cord injury following occlusion of the thoraco-abdominal aorta. To measure whether melatonin administered to rabbits before and after occlusion exerts an effect on the repair of ischemia-reperfusion (IR) injury. Medical Biology Laboratory, Inonu University, Malatya, Turkey. Rabbits were divided into three IR treatment groups and one sham-operated (ShOp) control group. The three treatment groups had their infrarenal aorta temporarily occluded for 25 min, while the ShOp group had laparotomy without aortic occlusion. Melatonin was administered either 10 min before aortic occlusion or 10 min after the clamp was removed. Physiologic saline was administered to the control animals. After treatment, the animals were euthanized and lumbosacral spinal cord tissue was removed for the determination of relevant enzyme activities. Malondialdehyde levels, indicating the extent of lipid peroxidation, were found to be significantly increased in the nonmelatonin treated (IR) group when compared to the ShOp group. Melatonin, whether given to pre- or post occlusion groups, suppressed malondialdehyde levels below that of the ShOp group. Catalase (CAT) and glutathione peroxidase (GSH-Px) enzyme activities were increased in the IR group compared to the ShOp group. Melatonin given preocclusion resulted in a significant decrease in both CAT and GSH-Px enzyme levels. The superoxide dismutase (SOD) enzyme activity was decreased in the ischemia-reperfusion treatment group. However, the melatonin treatment increased SOD enzyme activity to levels approximating that of the ShOp group. To our knowledge, this is the first study that shows the effects of melatonin administered both pre- and postischemia on induced oxidative damage to injured spinal cords. Our data also expands on reports that melatonin administration may significantly reduce the incidence of spinal cord injury following temporary aortic occlusion.

  4. Spinal cord ischemia following thoracotomy without epidural anesthesia.

    PubMed

    Raz, Aeyal; Avramovich, Aharon; Saraf-Lavi, Efrat; Saute, Milton; Eidelman, Leonid A

    2006-06-01

    Paraplegia is an uncommon yet devastating complication following thoracotomy, usually caused by compression or ischemia of the spinal cord. Ischemia without compression may be a result of global ischemia, vascular injury and other causes. Epidural anesthesia has been implicated as a major cause. This report highlights the fact that perioperative cord ischemia and paraplegia may be unrelated to epidural intervention. A 71-yr-old woman was admitted for a left upper lobectomy for resection of a non-small cell carcinoma of the lung. The patient refused epidural catheter placement and underwent a left T5-6 thoracotomy under general anesthesia. During surgery, she was hemodynamically stable and good oxygen saturation was maintained. Several hours following surgery the patient complained of loss of sensation in her legs. Neurological examination disclosed a complete motor and sensory block at the T5-6 level. Magnetic resonance imaging (MRI) revealed spinal cord ischemia. The patient received iv steroid treatment, but remained paraplegic. Five months following the surgery there was only partial improvement in her motor symptoms. A follow-up MRI study was consistent with a diagnosis of spinal cord ischemia. In this case of paraplegia following thoracic surgery for lung resection, epidural anesthesia/analgesia was not used. The MRI demonstrated evidence of spinal cord ischemia, and no evidence of cord compression. This case highlights that etiologies other than epidural intervention, such as injury to the spinal segmental arteries during thoracotomy, should be considered as potential causes of cord ischemia and resultant paraplegia in this surgical population.

  5. Does the intrathecal propofol have a neuroprotective effect on spinal cord ischemia?

    PubMed Central

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

    2015-01-01

    The neuroprotective effects of propofol have been confirmed. However, it remains unclear whether intrathecal administration of propofol exhibits neuroprotective effects on spinal cord ischemia. At 1 hour prior to spinal cord ischemia, propofol (100 and 300 µg) was intrathecally administered in rats with spinal cord ischemia. Propofol pre-treatment greatly improved rat pathological changes and neurological function deficits at 24 hours after spinal cord ischemia. These results suggest that intrathecal administration of propofol exhibits neuroprotective effects on spinal cord structural and functional damage caused by ischemia. PMID:26807119

  6. [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

  7. Shriners Hospital Spinal Cord Injury Self Care Manual.

    ERIC Educational Resources Information Center

    Fox, Carol

    This manual is intended for young people with spinal cord injuries who are receiving rehabilitation services within the Spinal Cord Injury Unit at Shriners Hospital (San Francisco, California). An introduction describes the rehabilitation program, which includes family conferences, an individualized program, an independent living program,…

  8. Spatial Elucidation of Spinal Cord Lipid- and Metabolite- Regulations in Amyotrophic Lateral Sclerosis

    NASA Astrophysics Data System (ADS)

    Hanrieder, Jörg; Ewing, Andrew G.

    2014-06-01

    Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressing disease of the central nervous system that is characterized by motor neuron degeneration in the brain stem and the spinal cord. We employed time of flight secondary ion mass spectrometry (ToF-SIMS) to profile spatial lipid- and metabolite- regulations in post mortem human spinal cord tissue from ALS patients to investigate chemical markers of ALS pathogenesis. ToF-SIMS scans and multivariate analysis of image and spectral data were performed on thoracic human spinal cord sections. Multivariate statistics of the image data allowed delineation of anatomical regions of interest based on their chemical identity. Spectral data extracted from these regions were compared using two different approaches for multivariate statistics, for investigating ALS related lipid and metabolite changes. The results show a significant decrease for cholesterol, triglycerides, and vitamin E in the ventral horn of ALS samples, which is presumably a consequence of motor neuron degeneration. Conversely, the biogenic mediator lipid lysophosphatidylcholine and its fragments were increased in ALS ventral spinal cord, pointing towards neuroinflammatory mechanisms associated with neuronal cell death. ToF-SIMS imaging is a promising approach for chemical histology and pathology for investigating the subcellular mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis.

  9. Novel aspects of spinal cord evoked potentials (SCEPs) in the evaluation of dorso-ventral and lateral mechanical impacts on the spinal cord.

    PubMed

    Rad, Iman; Kouhzaei, Sogolie; Mobasheri, Hamid; Saberi, Hooshang

    2015-02-01

    The aim of the current study was to mimic mechanical impacts on the spinal cord by manifesting the effects of dorsoventral (DVMP) and lateral (LMP) mechanical pressure on neural activity to address points to be considered during surgery for different purposes, including spinal cord decompression. Spinal cords of anesthetized rats were compressed at T13. Different characteristics of axons, including vulnerability, excitability, and conduction velocity (CV), in response to promptness, severity, and duration of pressure were assessed by spinal cord evoked potentials (SCEPs). Real-time SCEPs recorded at L4-5 revealed N1, N2, and N3 peaks that were used to represent the activity of injured sensory afferents, interneurons, and MN fibers. The averaged SCEP recordings were fitted by trust-region algorithm to find the equivalent Gaussian and polynomial equations. The pyramidal and extrapyramidal pathways possessed CVs of 3-11 and 16-80 m s(-1), respectively. DVMP decreased the excitability of myelinated neural fibers in antidromic and orthodromic pathways. The excitability of fibers in extrapyramidal and pyramidal pathways of lateral corticospinal (LCS) and anterior corticospinal (ACS) tracts decreased following LMP. A significant drop in the amplitude of N3 and its conduction velocity (CV) revealed higher susceptibility of less-myelinated fibers to both DVMP and LMP. The best parametric fitting model for triplet healthy spinal cord CAP was a six-term Gaussian equation (G6) that fell into a five-term equation (G5) at the complete compression stage. The spinal cord is more susceptible to dorsoventral than lateral mechanical pressures, and this should be considered in spinal cord operations. SCEPs have shown promising capabilities for evaluating the severity of SCI and thus can be applied for diagnostic or prognostic intraoperative monitoring (IOM).

  10. Novel aspects of spinal cord evoked potentials (SCEPs) in the evaluation of dorso-ventral and lateral mechanical impacts on the spinal cord

    NASA Astrophysics Data System (ADS)

    Rad, Iman; Kouhzaei, Sogolie; Mobasheri, Hamid; Saberi, Hooshang

    2015-02-01

    Objectives. The aim of the current study was to mimic mechanical impacts on the spinal cord by manifesting the effects of dorsoventral (DVMP) and lateral (LMP) mechanical pressure on neural activity to address points to be considered during surgery for different purposes, including spinal cord decompression. Approaches. Spinal cords of anesthetized rats were compressed at T13. Different characteristics of axons, including vulnerability, excitability, and conduction velocity (CV), in response to promptness, severity, and duration of pressure were assessed by spinal cord evoked potentials (SCEPs). Real-time SCEPs recorded at L4-5 revealed N1, N2, and N3 peaks that were used to represent the activity of injured sensory afferents, interneurons, and MN fibers. The averaged SCEP recordings were fitted by trust-region algorithm to find the equivalent Gaussian and polynomial equations. Main results. The pyramidal and extrapyramidal pathways possessed CVs of 3-11 and 16-80 m s-1, respectively. DVMP decreased the excitability of myelinated neural fibers in antidromic and orthodromic pathways. The excitability of fibers in extrapyramidal and pyramidal pathways of lateral corticospinal (LCS) and anterior corticospinal (ACS) tracts decreased following LMP. A significant drop in the amplitude of N3 and its conduction velocity (CV) revealed higher susceptibility of less-myelinated fibers to both DVMP and LMP. The best parametric fitting model for triplet healthy spinal cord CAP was a six-term Gaussian equation (G6) that fell into a five-term equation (G5) at the complete compression stage. Significance. The spinal cord is more susceptible to dorsoventral than lateral mechanical pressures, and this should be considered in spinal cord operations. SCEPs have shown promising capabilities for evaluating the severity of SCI and thus can be applied for diagnostic or prognostic intraoperative monitoring (IOM).

  11. 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.

  12. Microsurgical resection of intramedullary spinal cord ependymoma.

    PubMed

    McCormick, Paul C

    2014-09-01

    Ependymomas are the most commonly occurring intramedullary spinal cord tumor in adults. With few exceptions these tumors are histologically benign, although they exhibit some biologic variability with respect to growth rate. While unencapsulated, spinal ependymomas are non-infiltrative and present a clear margin of demarcation from the surrounding spinal cord that serves as an effective dissection plane. This video demonstrates the technique of microsurgical resection of an intramedullary ependymoma through a posterior midline myelotomy. The video can be found here: http://youtu.be/lcHhymSvSqU.

  13. 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.

  14. 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

  15. Nonlinear Viscoelastic Characterization of the Porcine Spinal Cord

    PubMed Central

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

    2014-01-01

    Although quasi-static and quasi-linear viscoelastic properties of the spinal cord have been reported previously, there are no published studies that have investigated the fully (strain-dependent) nonlinear viscoelastic properties of the spinal cord. In this study, stress relaxation experiments and dynamic cycling were performed on six fresh porcine lumbar cord specimens to examine their viscoelastic mechanical properties. The stress relaxation data were fitted to a modified superposition formulation and a novel finite ramp time correction technique was applied. The parameters obtained from this fitting methodology were used to predict the average dynamic cyclic viscoelastic behavior of the porcine cord. The data indicate that the porcine spinal cord exhibited fully nonlinear viscoelastic behavior. The average weighted RMSE for a Heaviside ramp fit was 2.8kPa, which was significantly greater (p < 0.001) than that of the nonlinear (comprehensive viscoelastic characterization (CVC) method) fit (0.365kPa). Further, the nonlinear mechanical parameters obtained were able to accurately predict the dynamic behavior, thus exemplifying the reliability of the obtained nonlinear parameters. These parameters will be important for future studies investigating various damage mechanisms of the spinal cord and studies developing high resolution finite elements models of the spine. PMID:24211612

  16. Musashi and Plasticity of Xenopus and Axolotl Spinal Cord Ependymal Cells

    PubMed Central

    Chernoff, Ellen A. G.; Sato, Kazuna; Salfity, Hai V. N.; Sarria, Deborah A.; Belecky-Adams, Teri

    2018-01-01

    The differentiated state of spinal cord ependymal cells in regeneration-competent amphibians varies between a constitutively active state in what is essentially a developing organism, the tadpole of the frog Xenopus laevis, and a quiescent, activatable state in a slowly growing adult salamander Ambystoma mexicanum, the Axolotl. Ependymal cells are epithelial in intact spinal cord of all vertebrates. After transection, body region ependymal epithelium in both Xenopus and the Axolotl disorganizes for regenerative outgrowth (gap replacement). Injury-reactive ependymal cells serve as a stem/progenitor cell population in regeneration and reconstruct the central canal. Expression patterns of mRNA and protein for the stem/progenitor cell-maintenance Notch signaling pathway mRNA-binding protein Musashi (msi) change with life stage and regeneration competence. Msi-1 is missing (immunohistochemistry), or at very low levels (polymerase chain reaction, PCR), in both intact regeneration-competent adult Axolotl cord and intact non-regeneration-competent Xenopus tadpole (Nieuwkoop and Faber stage 62+, NF 62+). The critical correlation for successful regeneration is msi-1 expression/upregulation after injury in the ependymal outgrowth and stump-region ependymal cells. msi-1 and msi-2 isoforms were cloned for the Axolotl as well as previously unknown isoforms of Xenopus msi-2. Intact Xenopus spinal cord ependymal cells show a loss of msi-1 expression between regeneration-competent (NF 50–53) and non-regenerating stages (NF 62+) and in post-metamorphosis froglets, while msi-2 displays a lower molecular weight isoform in non-regenerating cord. In the Axolotl, embryos and juveniles maintain Msi-1 expression in the intact cord. In the adult Axolotl, Msi-1 is absent, but upregulates after injury. Msi-2 levels are more variable among Axolotl life stages: rising between late tailbud embryos and juveniles and decreasing in adult cord. Cultures of regeneration-competent Xenopus tadpole

  17. Alterations of glutamate release in the spinal cord of mice with experimental autoimmune encephalomyelitis.

    PubMed

    Marte, Antonella; Cavallero, Anna; Morando, Sara; Uccelli, Antonio; Raiteri, Maurizio; Fedele, Ernesto

    2010-10-01

    We have investigated the spontaneous and the depolarisation-induced release of [(3)H]D-aspartate ([(3)H]D-ASP), a non-metabolisable analogue of glutamate, in spinal cord slices, synaptosomes and gliosomes from mice with experimental autoimmune encephalomyelitis (EAE) at 13, 21 and 55 days post-immunisation (d.p.i.), representing onset, peak and chronic phases of the pathology. At 13 and 21 d.p.i., the KCl-evoked, calcium-dependent overflow of [(3)H]D-ASP in spinal cord slices was significantly lower (30-40%), whereas at 55 d.p.i. it was significantly higher (30%), than that elicited in matched controls. When the release was measured from spinal cord synaptosomes and gliosomes in superfusion, a different picture emerged. The spontaneous and the KCl(15 mM)-induced release of [(3)H]D-ASP were significantly increased both in synaptosomes (17% and 45%, respectively) and gliosomes (26% and 25%, respectively) at 21, but not at 13, d.p.i. At 55 d.p.i., the KCl-induced [(3)H]D-ASP release was significantly increased (40%) only in synaptosomes. Finally, uptake of [(3)H]D-ASP was markedly (50-60%) increased in spinal cord synaptosomes, but not in gliosomes, obtained from EAE mice at 21 d.p.i., whereas no differences could be detected at 13 d.p.i. Our data indicate that glutamatergic neurotransmission is altered in the spinal cord of EAE mice. © 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry.

  18. Injury-induced ctgfa directs glial bridging and spinal cord regeneration in zebrafish

    PubMed Central

    Mokalled, Mayssa H.; Patra, Chinmoy; Dickson, Amy L.; Endo, Toyokazu; Stainier, Didier Y. R.; Poss, Kenneth D.

    2016-01-01

    Unlike mammals, zebrafish efficiently regenerate functional nervous system tissue after major spinal cord injury. Whereas glial scarring presents a roadblock for mammalian spinal cord repair, glial cells in zebrafish form a bridge across severed spinal cord tissue and facilitate regeneration, a relatively unexplored process. Here, we performed a genome-wide profiling screen for secreted factors that are upregulated during zebrafish spinal cord regeneration. We find that connective tissue growth factor a (ctgfa) is induced in and around glial cells that participate in initial bridging events. Mutations in ctgfa disrupt spinal cord repair, while transgenic ctgfa overexpression and local human CTGF recombinant protein delivery accelerate bridging and functional regeneration. Our study reveals that CTGF is necessary and sufficient to stimulate glial bridging and natural spinal cord regeneration. PMID:27811277

  19. Exercise-Dependent Modulation of Neurourological Health Following Spinal Cord Injury

    DTIC Science & Technology

    2014-11-01

    Neurobiology, 2Kentucky Spinal Cord Injury Research Center, 3Department of Neurological Surgery, 4Frazier Rehab Institute, University of Louisville...an infusion pump and pressure transducer.24 Behavioral procedures Training paradigm. Training interventions initiated acutely post-SCI may be...proper plantar placement—e.g. complete toe extension, no ankle rotation, and incorporation of forelimb-hindlimb coordination with minimal assistance

  20. 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

  1. 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...

  2. 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.

  3. Current pregnancy among women with spinal cord injury: findings from the US national spinal cord injury database.

    PubMed

    Iezzoni, L I; Chen, Y; McLain, A B J

    2015-11-01

    Cross-sectional study. To examine the prevalence of pregnancy and associations with sociodemographic and clinical factors among women with spinal cord injury (SCI). US National Spinal Cord Injury Database, an SCI registry that interviews participants 1, 5 and then every 5 years post injury. Data include SCI clinical details, functional impairments, participation measures, depressive symptoms and life satisfaction. Women aged 18-49 are asked about hospitalizations in the last year relating to pregnancy or its complications. Data represent 1907 women, who completed 3054 interviews. We used generalized estimating equations to examine bivariable associations between pregnancy and clinical and psychosocial variables and to perform multivariable regressions predicting pregnancy. Across all women, 2.0% reported pregnancy during the prior 12 months. This annual prevalence differed significantly by the years elapsed since injury; the highest rate occurred 15 years post injury (3.7%). Bivariable analyses found that younger age at injury was significantly associated with current pregnancy (P<0.0001). Compared with nonpregnant women, those reporting current pregnancy were significantly more likely to be married or partnered, have sport-related SCI, have higher motor scores and have more positive psychosocial status scores. Multivariable analyses found significant associations between current pregnancy and age, marital status, motor score and mobility and occupation scale scores. Current pregnancy rates among reproductive-aged women with SCI are similar to rates of other US women with chronic mobility impairments. More information is needed about pregnancy experiences and outcomes to inform both women with SCI seeking childbearing and clinicians providing their care.

  4. 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.

  5. 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

  6. Variations in the formation of the human caudal spinal cord.

    PubMed

    Saraga-Babić, M; Sapunar, D; Wartiovaara, J

    1995-01-01

    Collection of 15 human embryos between 4-8 developmental weeks was used to histologically investigate variations in the development of the caudal part of the spinal cord and the neighboring axial organs (notochord and vertebral column). In the 4-week embryo, two types of neurulation were parallelly observed along the anteroposterior body axis: primary in the areas cranial to the neuroporus caudalis and secondary in the more caudal tail regions. In the 5-week embryos, both parts of the neural tube fused, forming only one continuous lumen in the developing spinal cord. In the three examined embryos we found anomalous pattern of spinal cord formation. Caudal parts of these spinal cords displayed division of their central canal into two or three separate lumina, each surrounded by neuroepithelial layer. In the caudal area of the spinal cord, derived by secondary neurulation, formation of separate lumina was neither connected to any anomalous notochord or vertebral column formation, nor the appearance of any major axial disturbances. We suggest that development of the caudal part of the spinal cord differs from its cranial region not only in the type of neurulation, but also in the destiny of its derivatives and possible modes of abnormality formation.

  7. Spinal cord compression in two related Ursus arctos horribilis.

    PubMed

    Thomovsky, Stephanie A; Chen, Annie V; Roberts, Greg R; Schmidt, Carrie E; Layton, Arthur W

    2012-09-01

    Two 15-yr-old grizzly bear littermates were evaluated within 9 mo of each other with the symptom of acute onset of progressive paraparesis and proprioceptive ataxia. The most significant clinical examination finding was pelvic limb paresis in both bears. Magnetic resonance examinations of both bears showed cranial thoracic spinal cord compression. The first bear had left-sided extradural, dorsolateral spinal cord compression at T3-T4. Vertebral canal stenosis was also observed at T2-T3. Images of the second bear showed lateral spinal cord compression from T2-T3 to T4-T5. Intervertebral disk disease and associated spinal cord compression was also observed at T2-T3 and T3-T4. One grizzly bear continued to deteriorate despite reduced exercise, steroid, and antibiotic therapy. The bear was euthanized, and a necropsy was performed. The postmortem showed a spinal ganglion cyst that caused spinal cord compression at the level of T3-T4. Wallerian-like degeneration was observed from C3-T6. The second bear was prescribed treatment that consisted of a combination of reduced exercise and steroid therapy. He continued to deteriorate with these medical therapies and was euthanized 4 mo after diagnosis. A necropsy showed hypertrophy and protrusion of the dorsal longitudinal ligament at T2-T3 and T3-T4, with resulting spinal cord compression in this region. Wallerian-like degeneration was observed from C2-L1. This is one of few case reports that describes paresis in bears. It is the only case report, to the authors' knowledge, that describes spinal magnetic resonance imaging findings in a grizzly bear and also the only report that describes a cranial thoracic myelopathy in two related grizzly bears with neurologic signs.

  8. A brain-spine interface alleviating gait deficits after spinal cord injury in primates.

    PubMed

    Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Moraud, Eduardo Martin; Mignardot, Jean-Baptiste; Buse, Nicolas; Gandar, Jerome; Barraud, Quentin; Xing, David; Rey, Elodie; Duis, Simone; Jianzhong, Yang; Ko, Wai Kin D; Li, Qin; Detemple, Peter; Denison, Tim; Micera, Silvestro; Bezard, Erwan; Bloch, Jocelyne; Courtine, Grégoire

    2016-11-10

    Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain-computer interfaces have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis. Theoretically, this strategy could also restore control over leg muscle activity for walking. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges. Recently, it was shown in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion. Here we interface leg motor cortex activity with epidural electrical stimulation protocols to establish a brain-spine interface that alleviated gait deficits after a spinal cord injury in non-human primates. Rhesus monkeys (Macaca mulatta) were implanted with an intracortical microelectrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain-spine interface in intact (uninjured) monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain-spine interface restored weight-bearing locomotion of the paralysed leg on a treadmill and overground. The implantable components integrated in the brain-spine interface have all been approved for

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. Modification of spasticity by transcutaneous spinal cord stimulation in individuals with incomplete spinal cord injury

    PubMed Central

    Hofstoetter, Ursula S.; McKay, William B.; Tansey, Keith E.; Mayr, Winfried; Kern, Helmut; Minassian, Karen

    2014-01-01

    Context/objective To examine the effects of transcutaneous spinal cord stimulation (tSCS) on lower-limb spasticity. Design Interventional pilot study to produce preliminary data. Setting Department of Physical Medicine and Rehabilitation, Wilhelminenspital, Vienna, Austria. Participants Three subjects with chronic motor-incomplete spinal cord injury (SCI) who could walk ≥10 m. Interventions Two interconnected stimulating skin electrodes (Ø 5 cm) were placed paraspinally at the T11/T12 vertebral levels, and two rectangular electrodes (8 × 13 cm) on the abdomen for the reference. Biphasic 2 ms-width pulses were delivered at 50 Hz for 30 minutes at intensities producing paraesthesias but no motor responses in the lower limbs. Outcome measures The Wartenberg pendulum test and neurological recordings of surface-electromyography (EMG) were used to assess effects on exaggerated reflex excitability. Non-functional co-activation during volitional movement was evaluated. The timed 10-m walk test provided measures of clinical function. Results The index of spasticity derived from the pendulum test changed from 0.8 ± 0.4 pre- to 0.9 ± 0.3 post-stimulation, with an improvement in the subject with the lowest pre-stimulation index. Exaggerated reflex responsiveness was decreased after tSCS across all subjects, with the most profound effect on passive lower-limb movement (pre- to post-tSCS EMG ratio: 0.2 ± 0.1), as was non-functional co-activation during voluntary movement. Gait speed values increased in two subjects by 39%. Conclusion These preliminary results suggest that tSCS, similar to epidurally delivered stimulation, may be used for spasticity control, without negatively impacting residual motor control in incomplete SCI. Further study in a larger population is warranted. PMID:24090290

  14. Intractable Pruritus After Traumatic Spinal Cord Injury

    PubMed Central

    Crane, Deborah A; Jaffee, Kenneth M; Kundu, Anjana

    2009-01-01

    Background: This report describes a young woman with incomplete traumatic cervical spinal cord injury and intractable pruritus involving her dorsal forearm. Method: Case report. Findings: Anatomic distribution of the pruritus corresponded to the dermatomal distribution of her level of spinal cord injury and vertebral fusion. Symptoms were attributed to the spinal cord injury and possible cervical root injury. Pruritus was refractory to all treatments, including topical lidocaine, gabapentin, transcutaneous electrical nerve stimulation, intravenous Bier block, stellate ganglion block, and acupuncture. Conclusions: Further understanding of neuropathic pruritus is needed. Diagnostic workup of intractable pruritus should include advanced imaging to detect ongoing nerve root compression. If diagnostic studies suggest radiculopathy, epidural steroid injection should be considered. Because the autonomic nervous system may be involved in complex chronic pain or pruritic syndromes, sympatholysis via such techniques as stellate ganglion block might be effective. PMID:19777867

  15. 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.

  16. 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

  17. Characterization of the Antibody Response after Cervical Spinal Cord Injury

    PubMed Central

    Ulndreaj, Antigona; Tzekou, Apostolia; Mothe, Andrea J.; Siddiqui, Ahad M.; Dragas, Rachel; Tator, Charles H.; Torlakovic, Emina E.

    2017-01-01

    Abstract The immune system plays a critical and complex role in the pathobiology of spinal cord injury (SCI), exerting both beneficial and detrimental effects. Increasing evidence suggests that there are injury level–dependent differences in the immune response to SCI. Patients with traumatic SCI have elevated levels of circulating autoantibodies against components of the central nervous system, but the role of these antibodies in SCI outcomes remains unknown. In rodent models of mid-thoracic SCI, antibody-mediated autoimmunity appears to be detrimental to recovery. However, whether autoantibodies against the spinal cord are generated following cervical SCI (cSCI), the most common level of injury in humans, remains undetermined. To address this knowledge gap, we investigated the antibody responses following cSCI in a rat model of injury. We found increased immunoglobulin G (IgG) and IgM antibodies in the spinal cord in the subacute phase of injury (2 weeks), but not in more chronic phases (10 and 20 weeks). At 2 weeks post-cSCI, antibodies were detected at the injury epicenter and co-localized with the astroglial scar and neurons of the ventral horn. These increased levels of antibodies corresponded with enhanced activation of immune responses in the spleen. Higher counts of antibody-secreting cells were observed in the spleen of injured rats. Further, increased levels of secreted IgG antibodies and enhanced proliferation of T-cells in splenocyte cultures from injured rats were found. These findings suggest the potential development of autoantibody responses following cSCI in the rat. The impact of the post-traumatic antibody responses on functional outcomes of cSCI is a critical topic that requires further investigation. PMID:27775474

  18. 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 ...

  19. Low-Grade Inflammation and Spinal Cord Injury: Exercise as Therapy?

    PubMed Central

    da Silva Alves, Eduardo; de Aquino Lemos, Valdir; Ruiz da Silva, Francieli; Lira, Fabio Santos; dos Santos, Ronaldo Vagner Thomathieli; Rosa, João Paulo Pereira; Caperuto, Erico; Tufik, Sergio; de Mello, Marco Tulio

    2013-01-01

    An increase in the prevalence of obesity in people with spinal cord injury can contribute to low-grade chronic inflammation and increase the risk of infection in this population. A decrease in sympathetic activity contributes to immunosuppression due to the lower activation of immune cells in the blood. The effects of physical exercise on inflammatory parameters in individuals with spinal cord injury have not been well described. We conducted a review of the literature published from 1974 to 2012. This review explored the relationships between low-grade inflammation, spinal cord injury, and exercise to discuss a novel mechanism that might explain the beneficial effects of exercise involving an increase in catecholamines and cytokines in people with spinal cord injury. PMID:23533315

  20. 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.

  1. 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

    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.

  2. A prospective evaluation of a pressure ulcer prevention and management E-Learning Program for adults with spinal cord injury.

    PubMed

    Brace, Jacalyn A; Schubart, Jane R

    2010-08-01

    Pressure ulcers are a common complication of spinal cord injury (SCI). Pressure ulcer education programs for spinal cord injured individuals have been found to have a positive effect on care protocol adherence. A prospective study was conducted among hospitalized spinal cord-injured men and women to determine if viewing the Pressure Ulcer Prevention and Management Education for Adults with Spinal Cord Injury: E-Learning Program affects their knowledge scores. A 20-question multiple-choice pre-/post learning test was developed and validated by 12 rehabilitation nurses. Twenty (20) patients (13 men, seven women; mean age 49 years, [SD: 18.26] with injuries to the cervical [seven], thoracic [six], and lumbar [six] regions) volunteered. Most (42%) had completed high school and time since SCI ranged from 2 weeks to 27 years. Eighteen (18) participants completed both the pre- and post test. Of those, 16 showed improvement in pressure ulcer knowledge scores. The median scores improved from 65 (range 25 to 100) pre-program to 92.5 (range 75 to 100) post-program. Descriptive statistics, Student's t-test, and analysis of variance (ANOVA) were used to analyze the data. The results suggest that a single viewing of this e-learning program could improve pressure ulcer knowledge of hospitalized adults with SCI. Research to ascertain the effects of this and other educational programs on pressure ulcer rates is needed.

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

    PubMed

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

    2017-09-01

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

  4. Psychosocial outcome following spinal cord injury.

    PubMed

    Hammell, K R

    1994-11-01

    Studies have indicated that loss of social contact remains the primary complaint of people with head injuries many years after discharge. In an attempt to disentangle specific and nonspecific effects of head injury a study was undertaken to compare a group of 15 men with severe closed head injuries and their wives, with a group of 15 men with complete, traumatic spinal cord injuries and their partners (n = 60). Time since discharge extended from 4 months to several years. This paper focuses primarily upon the results and implication of the responses from the group of men with spinal cord injuries and their partners. The Interview Schedule for Social Interaction was correlated with the Leeds Scale for the Self Assessment of Anxiety and Depression. All groups reported low availability and adequacy of social integration and exhibited high levels of depression. The group of men with spinal cord injuries had the lowest scores for the availability of social integration, indicating that the social isolation which has previously been identified amongst people with head injuries may not be attributable solely to brain damage.

  5. The role of cation-dependent chloride transporters in neuropathic pain following spinal cord injury

    PubMed Central

    Cramer, Samuel W; Baggott, Christopher; Cain, John; Tilghman, Jessica; Allcock, Bradley; Miranpuri, Gurwattan; Rajpal, Sharad; Sun, Dandan; Resnick, Daniel

    2008-01-01

    Background Altered Cl- homeostasis and GABAergic function are associated with nociceptive input hypersensitivity. This study investigated the role of two major intracellular Cl- regulatory proteins, Na+-K+-Cl- cotransporter 1 (NKCC1) and K+-Cl- cotransporter 2 (KCC2), in neuropathic pain following spinal cord injury (SCI). Results Sprague-Dawley rats underwent a contusive SCI at T9 using the MASCIS impactor. The rats developed hyperalgesia between days 21 and 42 post-SCI. Thermal hyperalgesia (TH) was determined by a decrease in hindpaw thermal withdrawal latency time (WLT) between days 21 and 42 post-SCI. Rats with TH were then treated with either vehicle (saline containing 0.25% NaOH) or NKCC1 inhibitor bumetanide (BU, 30 mg/kg, i.p.) in vehicle. TH was then re-measured at 1 h post-injection. Administration of BU significantly increased the mean WLT in rats (p < 0.05). The group administered with the vehicle alone showed no anti-hyperalgesic effects. Moreover, an increase in NKCC1 protein expression occurred in the lesion epicenter of the spinal cord during day 2–14 post-SCI and peaked on day 14 post-SCI (p < 0.05). Concurrently, a down-regulation of KCC2 protein was detected during day 2–14 post-SCI. The rats with TH exhibited a sustained loss of KCC2 protein during post-SCI days 21–42. No significant changes of these proteins were detected in the rostral region of the spinal cord. Conclusion Taken together, expression of NKCC1 and KCC2 proteins was differentially altered following SCI. The anti-hyperalgesic effect of NKCC1 inhibition suggests that normal or elevated NKCC1 function and loss of KCC2 function play a role in the development and maintenance of SCI-induced neuropathic pain. PMID:18799000

  6. 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

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

    PubMed

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

    2017-12-01

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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. Current Pregnancy Among Women with Spinal Cord Injury: Findings from the U.S. National Spinal Cord Injury Database

    PubMed Central

    Iezzoni, Lisa I.; Chen, Yuying; McLain, Aime B. Jackson

    2015-01-01

    Study design Cross-sectional study Objective To examine prevalence of pregnancy and associations with sociodemographic and clinical factors among women with spinal cord injury (SCI) Setting U.S. National Spinal Cord Injury Database, an SCI registry that interviews participants 1, 5, and then every 5 years post-injury. Data include SCI clinical details, functional impairments, participation measures, depressive symptoms, and life satisfaction. Women ages 18-49 are asked about hospitalizations in the last year relating to pregnancy or its complications. Data represent 1,907 women, who completed 3,054 interviews. Methods We used generalized estimating equations to examine bivariable associations between pregnancy and clinical and psychosocial variables and to perform multivariable regressions predicting pregnancy. Results Across all women, 2.0% reported pregnancy during the prior 12 months. This annual prevalence differed significantly by years elapsed since injury; the highest rate occurred 15 years post-injury (3.7%). Bivariable analyses found that younger age at injury was significantly associated with current pregnancy (P < 0.0001). Compared with nonpregnant women, those reporting current pregancy were significantly more likely to be married or partnered, have sport-related SCI, have higher motor scores, and have more positive psychosocial status scores. Multivariable analyses found significant associations between current pregnancy and age, marital status, motor score, and mobility and occupation scale scores. Conclusions Current pregnancy rates among reproductive-aged women with SCI are similar to rates of other U.S. women with chronic mobility impairments. More information is needed about pregnancy experiences and outcomes to inform both women with SCI seeking childbearing and clinicians providing their care. PMID:25987000

  14. Spinal cord lesions in Bangladesh: an epidemiological study 1994 - 1995.

    PubMed

    Hoque, M F; Grangeon, C; Reed, K

    1999-12-01

    Spinal Cord Lesions are a major public health problem in Bangladesh. This epidemiological study was undertaken in order to identify the causes of spinal cord lesions and thus to allow prevention and control programs to be developed. The records of 247 patients with spinal cord lesions admitted to The Centre for the Rehabilitation of the Paralysed (CRP), Savar, Dhaka from January 1994 to June 1995 were reviewed retrospectively. Comparisons were made with the reports of studies from other countries, both developing and developed. The most common cause of traumatic lesions was a fall from a height followed by falling when carrying a heavy weight on the head and road traffic accidents. Most of the patients were between 20 - 40 years old and the overall age group ranged from 10 - 70 years. The male:female ratio was 7.5 : 1.0. Among the traumatic spinal cord lesions, 60% were paraplegics and 40% tetraplegics. Among the non-traumatic spinal cord lesions cases 84% were paraplegics and 16% tetraplegics. The leading cause of death resulted from respiratory complications and these deaths occurred in the very early period of admission. From the results it can be deduced that the high incidence of spinal cord lesion as a result from falls from a height, and from falling when carrying a heavy weight on the head, can be explained by the mainly agricultural based economy of Bangladesh. The most common age group (10 - 40 years) of patients reflects the socio-economic conditions of Bangladesh. The male:female ratio (7.5 : 1.0) of patients with a spinal cord lesion is due to the socio-economic status and to the traditional culture of the society.

  15. 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.

  16. Spinal cord injury with central cord syndrome from surfing.

    PubMed

    Steinfeld, Yaniv; Keren, Yaniv; Haddad, Elias

    2018-01-01

    Central cord syndrome (CCS) is an injury to the center of the spinal cord. It is well known as a hyperextension injury, but it has never been described as a surfing injury. Our report describes this injury in detail. A 35-year-old male novice surfer presented to the emergency department with acute tetraplegia following falling off his surfboard and hitting sea floor at a shallow beach break. He was rescued by a fellow surfer while floating in the sea and unable to raise his head above sea level. Upon arrival at the hospital, tetraplegia and sensory deficits were noted. Radiological investigations showed advanced spinal stenosis at C4-6 levels. T2 magnetic resonance imaging (MRI) demonstrated myelopathy at C5-C6 level. He was diagnosed as having central cord syndrome, treated conservatively, and regained near full neurologic recovery after a month of rehabilitation. Unique sport activities lead to unique injuries. It is important to accurately describe these injuries in order to create protective measures against them. Neurologic injuries in surfers are uncommon. With low-energy trauma, surfer's myelopathy is still the most common diagnosis, but central cord syndrome should be in the differential diagnosis.

  17. A massive open online course for teaching physiotherapy students and physiotherapists about spinal cord injuries.

    PubMed

    Harvey, L A; Glinsky, J V; Lowe, R; Lowe, T

    2014-12-01

    A descriptive audit. To audit the participation and satisfaction in a Massive Open Online Course (MOOC) for teaching physiotherapy students and physiotherapists about spinal cord injuries. Global and online. A 5-week MOOC about the physiotherapy management of spinal cord injuries was hosted by Physiopedia and run in partnership with the International Spinal Cord Society. The MOOC was based on the physiotherapy-specific module of www.elearnSCI.org, and also involved extra readings, activities and online discussion through a closed Facebook group. Participation and satisfaction was quantified through a pre- and post-MOOC knowledge assessment and an online course evaluation. Participation was also gauged through Facebook activity and internet-based usage statistics. Three thousand five hundred and twenty-three people from 108 countries registered for the MOOC and 2527 joined the Facebook group. One thousand one hundred and twenty-one completed the pre- and post-MOOC knowledge assessments, with more completing one or the other. The median (interquartile range) results for those who completed the pre and post-MOOC knowledge assessments were 70% (60-80%) and 90% (80-95%), respectively. One thousand and twenty-nine completed the online course evaluation, with more than 80% agreeing or strongly agreeing with 12 of the 13 positive statements posed to them about the course. Most participants who completed the MOOC performed well on the post-MOOC knowledge assessment and enjoyed the learning experience. However, these results may be biased if those who did not complete the MOOC were dissatisfied and/or did not sit the post-MOOC knowledge assessment.

  18. International urodynamic basic spinal cord injury data set.

    PubMed

    Biering-Sørensen, F; Craggs, M; Kennelly, M; Schick, E; Wyndaele, J-J

    2008-07-01

    To create the International Urodynamic 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 members appointed by the Neurourology Committee of 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 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 Urodynamic Basic SCI Data Set are date of data collection, bladder sensation during filling cystometry, detrusor function, compliance during filing cystometry, function during voiding, detrusor leak point pressure, maximum detrusor pressure, cystometric bladder capacity and post-void residual volume.

  19. 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.

  20. 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

  1. Prospective Study of the Use of Intraoperative Neuromonitoring in Determining Post-Operative Energy Requirements and Physiologic Midline in Spinal Cord Stimulation.

    PubMed

    Collison, Claire; Prusik, Julia; Paniccioli, Steven; Briotte, Michael; Grey, Rachael; Feustel, Paul; Pilitsis, Julie G

    2017-08-01

    Intraoperative neuromonitoring (IONM) through electromyography (EMG) studies has been shown to be a safe, effective way to determine the laterality of the spinal cord and guide electrode placement during spinal cord stimulation (SCS). However, the use of IONM to predict post-operative energy requirements and midline has not been examined and offers a new avenue to streamline programming and device selection. Further, the impact of cerebrospinal fluid (CSF) thickness on intraoperative and post-operative amplitudes is understood but has not been explicitly characterized. A total of 24 patients undergoing SCS implantation for chronic pain had intraoperative EMG studies performed to determine physiologic midline. The intraoperative midline was compared to the midline determined on post-operative day 1 based on paresthesia patterns during programming. For patients who had thoracic leads placed, the amplitudes needed to induce abdominal and extremity lateralization during SCS placement were compared with the intensities needed to induce therapy at post-operative day 1. Additionally, we examined whether CSF thickness, body mass index, diabetes, drug use, and smoking correlated with intraoperative and post-operative amplitudes. Intraoperative EMG was able to predict post-operative paresthesia-based midline in 70.83% of patients. There was a statistically significant relationship between the intraoperative intensity needed to induce extremity lateralization with the post-operative intensity to induce therapy (p = 0.009) as well as the intraoperative intensity needed to stimulate abdominals with the post-operative intensity (p = 0.033). There was also a relationship seen between CSF thickness and the post-operative energy requirements in patients (p = 0.039). EMG accurately predicts post-operative energy requirements and midline in SCS patients. While 29.17% of patients did not have a match between their intraoperative and post-operative midlines, EMG testing was

  2. 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.

  3. 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

  4. Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury

    PubMed Central

    2010-01-01

    Background Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from the brain correlates with the development of spasticity. Results Here we examine the dynamic transcriptional response of motor neurons to spinal cord injury as it evolves over time to unravel common gene expression patterns and their underlying regulatory mechanisms. For this we use a rat-tail-model with complete spinal cord transection causing injury-induced spasticity, where gene expression profiles are obtained from labeled motor neurons extracted with laser microdissection 0, 2, 7, 21 and 60 days post injury. Consensus clustering identifies 12 gene clusters with distinct time expression profiles. Analysis of these gene clusters identifies early immunological/inflammatory and late developmental responses as well as a regulation of genes relating to neuron excitability that support the development of motor neuron hyper-excitability and the reappearance of plateau potentials in the late phase of the injury response. Transcription factor motif analysis identifies differentially expressed transcription factors involved in the regulation of each gene cluster, shaping the expression of the identified biological processes and their associated genes underlying the changes in motor neuron excitability. Conclusions This analysis provides important clues to the underlying mechanisms of transcriptional regulation responsible for the increased excitability observed in motor neurons in the late chronic phase of spinal cord injury suggesting alternative targets for treatment of spinal cord injury. Several transcription factors were identified as potential regulators of gene clusters containing elements related to motor neuron hyper-excitability, the manipulation

  5. Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury.

    PubMed

    Ryge, Jesper; Winther, Ole; Wienecke, Jacob; Sandelin, Albin; Westerdahl, Ann-Charlotte; Hultborn, Hans; Kiehn, Ole

    2010-06-09

    Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from the brain correlates with the development of spasticity. Here we examine the dynamic transcriptional response of motor neurons to spinal cord injury as it evolves over time to unravel common gene expression patterns and their underlying regulatory mechanisms. For this we use a rat-tail-model with complete spinal cord transection causing injury-induced spasticity, where gene expression profiles are obtained from labeled motor neurons extracted with laser microdissection 0, 2, 7, 21 and 60 days post injury. Consensus clustering identifies 12 gene clusters with distinct time expression profiles. Analysis of these gene clusters identifies early immunological/inflammatory and late developmental responses as well as a regulation of genes relating to neuron excitability that support the development of motor neuron hyper-excitability and the reappearance of plateau potentials in the late phase of the injury response. Transcription factor motif analysis identifies differentially expressed transcription factors involved in the regulation of each gene cluster, shaping the expression of the identified biological processes and their associated genes underlying the changes in motor neuron excitability. This analysis provides important clues to the underlying mechanisms of transcriptional regulation responsible for the increased excitability observed in motor neurons in the late chronic phase of spinal cord injury suggesting alternative targets for treatment of spinal cord injury. Several transcription factors were identified as potential regulators of gene clusters containing elements related to motor neuron hyper-excitability, the manipulation of which potentially could be

  6. [Spanish validation of the International Spinal Cord Injury Pulmonary Function Basic Data Set questionnaire for the study of the repercussion of spinal cord injury in the respiratory system].

    PubMed

    Gómez Garrido, Alba; León Espitia, Ana María; Montesinos Magraner, Lluïsa; Ramirez Galceran, Lucrecia; Soler Canudes, Emilia; González Viejo, Miguel Angel

    2015-12-07

    The dysfunction of the respiratory system and the breathing complications in persons with injured spinal cord has an effect on the morbidity and the mortality of the disease. The objectives were: 1) to translate to Spanish and validate the questionnaire of international consensus: International Spinal Cord Injury Pulmonary Function Basic Data Set, and 2) to determine the influence of chronic spinal cord injury in the respiratory system in terms of respiratory functionalism. Translation to Spanish and validation of the questionnaire of international consensus intended for the study of the pulmonary function in spinal cord injury disease. We tested the reliability of that questionnaire. We conducted a descriptive transversal study to determine the degree of involvement of the respiratory system in spinal cord injury. A percentage of 91.9 did not have any respiratory pathology before spinal cord injury and 54.8% of patients smoked. A percentage of 27.4 of patients presented breathing complications one year after the injury. Results of the respiratory function tests were: FVC 67%, FEV1 72% and PEF 70%. Concordance and reliability were 98%. The Spanish version of the questionnaire of international consensus about the pulmonary function is a useful tool for the study of the respiratory involvement in spinal cord injury. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  7. Spinal column and spinal cord injuries in mountain bikers: a 13-year review.

    PubMed

    Dodwell, Emily R; Kwon, Brian K; Hughes, Barbara; Koo, David; Townson, Andrea; Aludino, Allan; Simons, Richard K; Fisher, Charles G; Dvorak, Marcel F; Noonan, Vanessa K

    2010-08-01

    Multiple studies have described in general the injuries associated with mountain biking, and detailed accounts of spine injuries sustained in hockey, gymnastics, skiing, snowboarding, rugby, and paragliding have previously been published. However, no large-scale detailed assessment of mountain biking associated spinal fractures and spinal cord injuries has previously been published. This study was undertaken to describe the patient demographics, injuries, mechanisms, treatments, outcomes, and resource requirements associated with spine injuries sustained while mountain biking. Case series; Level of evidence, 4. Patients who were injured while mountain biking, and who were seen at a provincial spine referral center between 1995 and 2007 inclusive, with spinal cord injuries and/or spine fracture were included. A chart review was performed to obtain demographic data, and details of the injury, treatment, outcome, and resource requirements. A total of 102 men and 5 women were identified for inclusion. The mean age at injury was 32.7 years (95% confidence interval 30.6, 35.0). Seventy-nine patients (73.8%) sustained cervical injuries, while the remainder sustained thoracic or lumbar injuries. Forty-three patients (40.2%) sustained a spinal cord injury. Of those with cord injuries, 18 (41.9%) were American Spinal Injury Association (ASIA) A, 5 (11.6%) were ASIA B, 10 (23.3%) ASIA C, and 10 (23.3%) ASIA D. Sixty-seven patients (62.6%) required surgical treatment. The mean length of stay in an acute hospital bed was 16.9 days (95% confidence interval 13.1, 30.0). Thirty-three patients (30.8%) required intensive care unit attention, and 31 patients (29.0%) required inpatient rehabilitation. Of the 43 patients (40.2%) seen with spinal cord injuries, 14 (32.5%) improved by 1 ASIA category, and 1 (2.3%) improved by 2 ASIA categories. Two patients remained ventilator-dependent at discharge. Spine fractures and spinal cord injuries caused by mountain biking accidents typically

  8. Multifocal Spinal Cord Nephroblastoma in a Dog.

    PubMed

    Henker, L C; Bianchi, R M; Vargas, T P; de Oliveira, E C; Driemeier, D; Pavarini, S P

    2018-01-01

    A 1-year-old male American pit bull terrier was presented with a history of proprioceptive deficits and mild lameness of the right hindlimb, which progressed after 5 months to paraparesis, culminating in tetraparesis after 2 weeks. Necropsy findings were limited to the spinal cord and consisted of multiple, intradural, extramedullary, slightly red masses which produced segmental areas of medullary swelling located in the cervical intumescence, thoracolumbar column, sacral segment and cauda equina. Histological evaluation revealed a tumour, composed of epithelial, stromal and blastemal cells, with structures resembling tubules, acini and embryonic glomeruli. Immunohistochemical labelling for vimentin, cytokeratin and S100 was positive for the stromal, epithelial and blastemal cells, respectively. A final diagnosis of multifocal spinal cord nephroblastoma was established. This is the first report of such a tumour showing concomitant involvement of the cervicothoracic, thoracolumbar, sacral and cauda equina areas of the spinal cord. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Vocational outcome following spinal cord injury.

    PubMed

    Conroy, L; McKenna, K

    1999-09-01

    Non-experimental (ex post facto) survey research design involving the use of a fixed alternative format questionnaire. To investigate variables influencing vocational outcome, to identify barriers to gaining and sustaining employment and to identify the effects of variables on the type of work engaged in following spinal cord injury. The two sets of independent variables considered were, individual and injury-related factors (age at onset of injury, time since injury, extent/level of injury, highest educational qualification achieved pre-injury, and pre-injury occupation) and circumstantial factors (means of transport, access difficulties, perceived workplace discrimination, financial disincentives to work and perceived level of skill). The Princess Alexandra Hospital Spinal Injuries Unit, Queensland, Australia. Data on the variables and the vocational outcomes of having ever worked or studied post-injury, current employment status and post-injury occupation were obtained from survey responses. Demographical and medical data were gathered from medical records. Forward stepwise logistic regression revealed that having ever worked or studied post-injury was associated with all individual and injury-related factors except pre-injury occupation, and two circumstantial factors, namely means of transport and access difficulties. Current employment was associated with all circumstantial factors as well as age at injury and pre-injury occupation. Standard multiple regression analyses revealed that post-injury occupation was correlated with all individual and injury-related factors as well as means of transport and perceived workplace discrimination. Tailored rehabilitation programs for individuals with characteristics associated with less successful vocational outcomes may facilitate their employment status after injury.

  10. 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.

  11. [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.

  12. Fast and accurate semi-automated segmentation method of spinal cord MR images at 3T applied to the construction of a cervical spinal cord template.

    PubMed

    El Mendili, Mohamed-Mounir; Chen, Raphaël; Tiret, Brice; Villard, Noémie; Trunet, Stéphanie; Pélégrini-Issac, Mélanie; Lehéricy, Stéphane; Pradat, Pierre-François; Benali, Habib

    2015-01-01

    To design a fast and accurate semi-automated segmentation method for spinal cord 3T MR images and to construct a template of the cervical spinal cord. A semi-automated double threshold-based method (DTbM) was proposed enabling both cross-sectional and volumetric measures from 3D T2-weighted turbo spin echo MR scans of the spinal cord at 3T. Eighty-two healthy subjects, 10 patients with amyotrophic lateral sclerosis, 10 with spinal muscular atrophy and 10 with spinal cord injuries were studied. DTbM was compared with active surface method (ASM), threshold-based method (TbM) and manual outlining (ground truth). Accuracy of segmentations was scored visually by a radiologist in cervical and thoracic cord regions. Accuracy was also quantified at the cervical and thoracic levels as well as at C2 vertebral level. To construct a cervical template from healthy subjects' images (n=59), a standardization pipeline was designed leading to well-centered straight spinal cord images and accurate probability tissue map. Visual scoring showed better performance for DTbM than for ASM. Mean Dice similarity coefficient (DSC) was 95.71% for DTbM and 90.78% for ASM at the cervical level and 94.27% for DTbM and 89.93% for ASM at the thoracic level. Finally, at C2 vertebral level, mean DSC was 97.98% for DTbM compared with 98.02% for TbM and 96.76% for ASM. DTbM showed similar accuracy compared with TbM, but with the advantage of limited manual interaction. A semi-automated segmentation method with limited manual intervention was introduced and validated on 3T images, enabling the construction of a cervical spinal cord template.

  13. Fast and Accurate Semi-Automated Segmentation Method of Spinal Cord MR Images at 3T Applied to the Construction of a Cervical Spinal Cord Template

    PubMed Central

    El Mendili, Mohamed-Mounir; Trunet, Stéphanie; Pélégrini-Issac, Mélanie; Lehéricy, Stéphane; Pradat, Pierre-François; Benali, Habib

    2015-01-01

    Objective To design a fast and accurate semi-automated segmentation method for spinal cord 3T MR images and to construct a template of the cervical spinal cord. Materials and Methods A semi-automated double threshold-based method (DTbM) was proposed enabling both cross-sectional and volumetric measures from 3D T2-weighted turbo spin echo MR scans of the spinal cord at 3T. Eighty-two healthy subjects, 10 patients with amyotrophic lateral sclerosis, 10 with spinal muscular atrophy and 10 with spinal cord injuries were studied. DTbM was compared with active surface method (ASM), threshold-based method (TbM) and manual outlining (ground truth). Accuracy of segmentations was scored visually by a radiologist in cervical and thoracic cord regions. Accuracy was also quantified at the cervical and thoracic levels as well as at C2 vertebral level. To construct a cervical template from healthy subjects’ images (n=59), a standardization pipeline was designed leading to well-centered straight spinal cord images and accurate probability tissue map. Results Visual scoring showed better performance for DTbM than for ASM. Mean Dice similarity coefficient (DSC) was 95.71% for DTbM and 90.78% for ASM at the cervical level and 94.27% for DTbM and 89.93% for ASM at the thoracic level. Finally, at C2 vertebral level, mean DSC was 97.98% for DTbM compared with 98.02% for TbM and 96.76% for ASM. DTbM showed similar accuracy compared with TbM, but with the advantage of limited manual interaction. Conclusion A semi-automated segmentation method with limited manual intervention was introduced and validated on 3T images, enabling the construction of a cervical spinal cord template. PMID:25816143

  14. Significance of fixation of the vertebral column for spinal cord injury experiments.

    PubMed

    Liu, Fei; Luo, Zhuo-Jin; You, Si-Wei; Jiao, Xi-Ying; Meng, Xiao-Mei; Shi, Ming; Wang, Chun-Ting; Ju, Gong

    2003-08-01

    Thoracic spinal cord transections were performed in adult rats. The animals were divided into two groups, with or without internal fixation of the involved vertebral column. Histologic and immunohistochemical studies were performed to compare the effect of internal fixation of the vertebral column. To find out the aspects and extent of beneficial effects of vertebral column fixation for spinal cord repair. Vertebral column fixation is a routine procedure in clinical spinal cord surgery. Paradoxically, most, if not all, animal spinal cord experiments seem to have ignored the importance of vertebral column fixation. During trunk movements, the vertebral column flexes to different directions, accompanied by bending of the spinal cord. Following spinal cord lesions, with frequent bending of the cord there will be repeated bleeding, inflammation, and other pathologic processes at the lesion site. Thus, the healing process will be hampered. The severity of the damages that will be brought about by bending of the cord is, to a certain degree, unpredictable. There will be rather big individual variations in injury and repair among the same type of experiments, rendering quantification and conclusion difficult. Adult Sprague-Dawley rats were used. The thoracic spinal cord was transected. Strong stainless steel wires were used for internal fixation of the vertebral column. The histology of the horizontal sections of the spinal cord segment, which included the lesion site, was examined at the 14th postoperative day. The volumes of the secondary degeneration and meningeal scar, the gap between the borders of the proximal and distal stumps of the transected spinal cord, the thickness of the meningeal scar, the astrocytic reaction, and the abundance of regenerating nerve fibers at the lesion site were compared between the vertebral column fixed and nonfixed groups. Whenever possible, the results were evaluated quantitatively. In all these aspects, the internally fixed group was

  15. Expression of the repulsive guidance molecule RGM and it receptor Neogenin after spinal cord injury in sea lamprey

    PubMed Central

    Shifman, Michael I.; Yumul, Rae Eden; Laramore, Cindy; Selzer, Michael E.

    2009-01-01

    The sea lamprey recovers normal-appearing locomotion after spinal cord transection and its spinal axons regenerate selectively in their correct paths. However, among identified reticulospinal neurons some are consistently bad regenerators and only about 50% of severed reticulospinal axons regenerate through the site of injury. We previously suggested (Shifman and Selzer, 2000) that selective chemorepulsion might explain why some neurons are bad regenerators and others not. To explore the role of additional chemorepulsive axonal guidance molecules during regeneration, we examined the expression of the repulsive guidance molecule (RGM) and its receptor neogenin by in situ hybridization and quantitative PCR. RGM mRNA was expressed in the spinal cord, primarily in neurons of the lateral gray matter and in dorsal cells. Following spinal cord transection, RGM message was downregulated in neurons close (within 10 mm) to the transection at 2 and 4 weeks, although it was upregulated in reactive microglia at 2 weeks post-transection. Neogenin mRNA expression was unchanged in the brainstem after spinal cord transection, and among the identified reticulospinal neurons, was detected only in “bad regenerators, Neurons that are known to regenerate well never expressed neogenin. The downregulation of RGM expression in neurons near the transection may increase the probability that regenerating axons will regenerate through the site of injury and entered caudal spinal cord. PMID:19268666

  16. Human iPS cell-derived astrocyte transplants preserve respiratory function after spinal cord injury

    PubMed Central

    Li, Ke; Javed, Elham; Scura, Daniel; Hala, Tamara J.; Seetharam, Suneil; Falnikar, Aditi; Richard, Jean-Philippe; Chorath, Ashley; Maragakis, Nicholas J.; Wright, Megan C.; Lepore, Angelo C.

    2015-01-01

    Transplantation-based replacement of lost and/or dysfunctional astrocytes is a promising therapy for spinal cord injury (SCI) that has not been extensively explored, despite the integral roles played by astrocytes in the central nervous system (CNS). Induced pluripotent stem (iPS) cells are a clinically-relevant source of pluripotent cells that both avoid ethical issues of embryonic stem cells and allow for homogeneous derivation of mature cell types in large quantities, potentially in an autologous fashion. Despite their promise, the iPS cell field is in its infancy with respect to evaluating in vivo graft integration and therapeutic efficacy in SCI models. Astrocytes express the major glutamate transporter, GLT1, which is responsible for the vast majority of glutamate uptake in spinal cord. Following SCI, compromised GLT1 expression/function can increase susceptibility to excitotoxicity. We therefore evaluated intraspinal transplantation of human iPS cell-derived astrocytes (hIPSAs) following cervical contusion SCI as a novel strategy for reconstituting GLT1 expression and for protecting diaphragmatic respiratory neural circuitry. Transplant-derived cells showed robust long-term survival post-injection and efficiently differentiated into astrocytes in injured spinal cord of both immunesuppressed mice and rats. However, the majority of transplant-derived astrocytes did not express high levels of GLT1, particularly at early times post-injection. To enhance their ability to modulate extracellular glutamate levels, we engineered hIPSAs with lentivirus to constitutively express GLT1. Overexpression significantly increased GLT1 protein and functional GLT1-mediated glutamate uptake levels in hIPSAs both in vitro and in vivo post-transplantation. Compared to human fibroblast control and unmodified hIPSA transplantation, GLT1-overexpressing hIPSAs reduced (1) lesion size within the injured cervical spinal cord, (2) morphological denervation by respiratory phrenic motor

  17. Human iPS cell-derived astrocyte transplants preserve respiratory function after spinal cord injury.

    PubMed

    Li, Ke; Javed, Elham; Scura, Daniel; Hala, Tamara J; Seetharam, Suneil; Falnikar, Aditi; Richard, Jean-Philippe; Chorath, Ashley; Maragakis, Nicholas J; Wright, Megan C; Lepore, Angelo C

    2015-09-01

    Transplantation-based replacement of lost and/or dysfunctional astrocytes is a promising therapy for spinal cord injury (SCI) that has not been extensively explored, despite the integral roles played by astrocytes in the central nervous system (CNS). Induced pluripotent stem (iPS) cells are a clinically-relevant source of pluripotent cells that both avoid ethical issues of embryonic stem cells and allow for homogeneous derivation of mature cell types in large quantities, potentially in an autologous fashion. Despite their promise, the iPS cell field is in its infancy with respect to evaluating in vivo graft integration and therapeutic efficacy in SCI models. Astrocytes express the major glutamate transporter, GLT1, which is responsible for the vast majority of glutamate uptake in spinal cord. Following SCI, compromised GLT1 expression/function can increase susceptibility to excitotoxicity. We therefore evaluated intraspinal transplantation of human iPS cell-derived astrocytes (hIPSAs) following cervical contusion SCI as a novel strategy for reconstituting GLT1 expression and for protecting diaphragmatic respiratory neural circuitry. Transplant-derived cells showed robust long-term survival post-injection and efficiently differentiated into astrocytes in injured spinal cord of both immunesuppressed mice and rats. However, the majority of transplant-derived astrocytes did not express high levels of GLT1, particularly at early times post-injection. To enhance their ability to modulate extracellular glutamate levels, we engineered hIPSAs with lentivirus to constitutively express GLT1. Overexpression significantly increased GLT1 protein and functional GLT1-mediated glutamate uptake levels in hIPSAs both in vitro and in vivo post-transplantation. Compared to human fibroblast control and unmodified hIPSA transplantation, GLT1-overexpressing hIPSAs reduced (1) lesion size within the injured cervical spinal cord, (2) morphological denervation by respiratory phrenic motor

  18. 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).

  19. Methylene Blue Mitigates Acute Neuroinflammation after Spinal Cord Injury through Inhibiting NLRP3 Inflammasome Activation in Microglia.

    PubMed

    Lin, Zhi-Hang; Wang, Si-Yuan; Chen, Li-Li; Zhuang, Jia-Yuan; Ke, Qing-Feng; Xiao, Dan-Rui; Lin, Wen-Ping

    2017-01-01

    The spinal cord injury (SCI) is a detrimental neurological disease involving the primary mechanical injury and secondary inflammatory damage. Curtailing the detrimental neuroinflammation would be beneficial for spinal cord function recovery. Microglia reside in the spinal cord and actively participate in the onset, progression and perhaps resolution of post-SCI neuroinflammation. In the current study, we tested the effects of methylene blue on microglia both in vitro and in a rat SCI model. We found that methylene blue inhibited the protein levels of IL-1β and IL-18 rather than their mRNA levels in activated microglia. Further investigation indicated that methylene blue deceased the activation of NLRP3 inflammasome and NLRC4 inflammasome in microglia in vitro . Moreover, in the rat SCI model, the similar effect of methylene blue on post-SCI microglia was also observed, except that the activation of NLRC4 inflammasome was not seen. The inhibition of microglia NLRP3 inflammasome was associated with down-regulation of intracellular reactive oxygen species (ROS). The administration of methylene blue mitigated the overall post-SCI neuroinflammation, demonstrated by decreased pro-inflammatory cytokine production and leukocyte infiltrates. Consequently, the neuronal apoptosis was partially inhibited and the hind limb locomotor function was ameliorated by methylene blue treatment. Our research highlights the role of methylene blue in inhibiting post-SCI neuroinflammation, and suggests that methylene blue might be used for SCI therapy.

  20. 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.

  1. 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

  2. Health behavior in persons with spinal cord injury: development and initial validation of an outcome measure.

    PubMed

    Pruitt, S D; Wahlgren, D R; Epping-Jordan, J E; Rossi, A L

    1998-10-01

    To describe the development and initial psychometric properties of a new outcome measure for health behaviors that delay or prevent secondary impairments associated with spinal cord injury (SCI). Persons with SCI were surveyed during routine annual physical evaluations. Veterans Affairs Medical Center Spinal Cord Injury Unit, which specializes in primary care for persons with SCI. Forty-nine persons with SCI, aged 19-73 years, 1-50 years post-SCI. The newly developed Spinal Cord Injury Lifestyle Scale (SCILS). Internal consistency is high (alpha = 0.81). Correlations between clinicians' ratings of participants' health behavior and the new SCILS provide preliminary support for construct validity. The SCILS is a brief, self-report measure of health-related behavior in persons with SCI. It is a promising new outcome measure to evaluate the effectiveness of clinical and educational efforts for health maintenance and prevention of secondary impairments associated with SCI.

  3. 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...

  4. 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...

  5. 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.

  6. 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.

  7. Proteomic Analysis Reveals Differentially Regulated Protein Acetylation in Human Amyotrophic Lateral Sclerosis Spinal Cord

    PubMed Central

    Azadzoi, Kazem; Yang, Yun; Fei, Zhou; Dou, Kefeng; Kowall, Neil W.; Choi, Han-Pil; Vieira, Fernando; Yang, Jing-Hua

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurodegenerative disease that primarily affects motor neurons in the brain and spinal cord. Histone deacetylase (HDAC) inhibitors have neuroprotective effects potentially useful for the treatment of neurodegenerative diseases including ALS; however, the molecular mechanisms underlying their potential efficacy is not well understood. Here we report that protein acetylation in urea-soluble proteins is differently regulated in post-mortem ALS spinal cord. Two-dimensional electrophoresis (2-DE) analysis reveals several protein clusters with similar molecular weight but different charge status. Liquid chromatography and tandem mass spectrometry (LC-MS/MS) identifies glial fibrillary acidic protein (GFAP) as the dominant component in the protein clusters. Further analysis indicates six heavily acetylated lysine residues at positions 89, 153, 189, 218, 259 and 331 of GFAP. Immunoprecipitation followed by Western blotting confirms that the larger form of GFAP fragments are acetylated and upregulated in ALS spinal cord. Further studies demonstrate that acetylation of the proteins additional to GFAP is differently regulated, suggesting that acetylation and/or deacetylation play an important role in pathogenesis of ALS. PMID:24312501

  8. Modeling the neuroanatomic propagation of ALS in the spinal cord

    NASA Astrophysics Data System (ADS)

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

    2017-07-01

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

  9. 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.

  10. [Rehabilitation programme using neuromuscular electrical stimulation in spinal cord: epidemiological aspects].

    PubMed

    Bittar, Cíntia Kelly; Cliquet, Alberto

    2011-01-01

    To assess epidemiological profile of spinal cord injury outpatients which have been participating of rehabilitation programme using neuromuscular electrical stimulation, in order to implement campaigns for preventing spinal cord trauma. From January to April 2009, 30 patients at the spinal cord injury ambulatory clinic at Hospital das Clínicas of Unicamp were analysed by some epidemiologic characteristics: age, profession, type and level of their paralysis, origin and time of injury. All patients had complete spinal cord injury (ASIA); 24 patients were men and six were women, the mean age was 34.6 years (range, 10-64 years), two patients were children. Twenty-one patients were paraplegic and nine were tetraplegic; causes included automobile accident (12), run over (three), diving (four), bicycle accident (one), motorcycle accident (three), gunshot wound (six), thoracic tuberculosis (one), and lumbar surgery (one). The mean lesion time was 8.2 years (range, 1-15 years). Two patients were retired. The results suggested that spinal cord injury affects mainly young active men. It is necessary to develop incisive actions to prevent accidents, specially directed to traffic security.

  11. Thoracic Unilateral Spinal Cord Injury After Spinal Anaesthesia for Total Hip Replacement: Fate or Mistake?

    PubMed Central

    Fabio, Costa; Romualdo, Del Buono; Eugenio, Agrò Felice; Vittoradolfo, Tambone; Massimiliano, Vitali Andrea; Giovanna, Ricci

    2017-01-01

    Spinal anaesthesia is the most preffered anesthesia technique for total hip replacement, and its complications range from low entity (insignificant) to life threatening. The incidence of neurologic complications after neuraxial anaesthesia is not perfectly clear, although there are several described cases of spinal cord ischaemia. We present a case of unilateral T8–T11 spinal cord ischaemia following L2–L3 spinal anaesthesia for total hip replacement. Magnetic resonance imaging showed a hyperintense T8–T11 signal alteration on the leftside of paramedian spinal cord. A temporal epidemiologic linkage between the damage and the surgery seems to be present. The injury occurred without anatomical proximity between the injury site and the spinal needle entry site. This may be due to multiple contributing factors, each of them is probably not enough to determine the damage by itself; however, acting simultaneously, they could have been responsible for the complication. The result was unpredictable and unavoidable and was caused by unforeseeable circumstances and not by inadequate medical practice. PMID:28439446

  12. 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.

  13. 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.

  14. 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

  15. Spinal cord grey matter segmentation challenge.

    PubMed

    Prados, Ferran; Ashburner, John; Blaiotta, Claudia; Brosch, Tom; Carballido-Gamio, Julio; Cardoso, Manuel Jorge; Conrad, Benjamin N; Datta, Esha; Dávid, Gergely; Leener, Benjamin De; Dupont, Sara M; Freund, Patrick; Wheeler-Kingshott, Claudia A M Gandini; Grussu, Francesco; Henry, Roland; Landman, Bennett A; Ljungberg, Emil; Lyttle, Bailey; Ourselin, Sebastien; Papinutto, Nico; Saporito, Salvatore; Schlaeger, Regina; Smith, Seth A; Summers, Paul; Tam, Roger; Yiannakas, Marios C; Zhu, Alyssa; Cohen-Adad, Julien

    2017-05-15

    An important image processing step in spinal cord magnetic resonance imaging is the ability to reliably and accurately segment grey and white matter for tissue specific analysis. There are several semi- or fully-automated segmentation methods for cervical cord cross-sectional area measurement with an excellent performance close or equal to the manual segmentation. However, grey matter segmentation is still challenging due to small cross-sectional size and shape, and active research is being conducted by several groups around the world in this field. Therefore a grey matter spinal cord segmentation challenge was organised to test different capabilities of various methods using the same multi-centre and multi-vendor dataset acquired with distinct 3D gradient-echo sequences. This challenge aimed to characterize the state-of-the-art in the field as well as identifying new opportunities for future improvements. Six different spinal cord grey matter segmentation methods developed independently by various research groups across the world and their performance were compared to manual segmentation outcomes, the present gold-standard. All algorithms provided good overall results for detecting the grey matter butterfly, albeit with variable performance in certain quality-of-segmentation metrics. The data have been made publicly available and the challenge web site remains open to new submissions. No modifications were introduced to any of the presented methods as a result of this challenge for the purposes of this publication. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Release of neuropeptide FF (FLFQPQRF-NH2) from rat spinal cord.

    PubMed

    Zhu, J; Jhamandas, K; Yang, H Y

    1992-10-02

    Neuropeptide FF (FLFQPQRF-NH2), originally isolated from bovine brain, is an FMRF-NH2-like peptide with morphine-modulating activity. Neuropeptide FF (NPFF) is highly localized in the dorsal spinal cords where there are also specific NPFF binding sites. Furthermore, there have been studies indicating that NPFF may participate in the regulation of pain threshold in the spinal cord. However, whether NPFF can be released from the spinal cord is not known. The present experiments, using an in vitro superfusion of an isolated whole rat spinal cord, demonstrated that high concentrations of KCl or substance P caused a release of NPFF immunoreactive material (IR) from the spinal cord into the perfusion medium in a calcium-dependent manner. Substance P (1-11) also produced a detectable release of NPFF-IR in vivo although the response was quite variable. The released NPFF-IR was analyzed by an HPLC study and found to consist of NPFF and other minor immunoreactive peptides. Further studies with substance P-related peptides showed that the in vitro release of NPFF-IR could also be induced by substance P (1-7) but not by [pGlu5,Me-Phe8,Sar9]-substance P (5-11) or substance K. These results suggest that the specific substance P receptor (SP-N), which is recognized by both substance P (1-11) and substance P (1-7) rather than the tachykinin receptor, is involved in NPFF secretion from the spinal cord. In view of the role of substance P (1-11) and substance P (1-7) in sensory transmission, the results of this study further support the role of NPFF in the modulation of antinociception in the spinal cord.

  17. 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.

  18. Using peer mentoring for people with spinal cord injury to enhance self-efficacy beliefs and prevent medical complications.

    PubMed

    Ljungberg, Inger; Kroll, Thilo; Libin, Alexander; Gordon, Samuel

    2011-02-01

    Individuals with spinal cord injury/disease are faced with a myriad of psychosocial adjustment challenges. This article describes the implementation of a peer-mentoring programme designed to support this adjustment process for people with SCI/disease and the programme's believed impact on self-efficacy and prevention of medical complications. With shorter length of stay in acute inpatient rehabilitation after spinal cord injury/disease, peer mentor programmes are becoming an important component to assist with education and community re-integration. Quasi-experimental non-controlled pretest/post-test. Patients with newly acquired spinal cord injury/disease participated in a one-year spinal cord injury peer-mentoring programme. Peer mentors met with their assigned participants regularly during inpatient care and on discharge to track medical complications and assist with adjusting to life after spinal cord injury/disease. In all, of 37 mentees enrolled, 24 successfully completed the programme. Sixty-seven per cent showed improved self-efficacy score between the two time points. Medical complications and doctor visits all decreased significantly between 0-6 months and 7-12 months. Our findings indicate that the older an individual is, the lower the likelihood of having a urinary tract infection (p = 0.006). The programme was well received by all mentees who felt they could connect well with their peer mentor. Peer mentoring in a rehabilitation setting enhances the understanding of challenges that patients and medical staff deal with on a day-to-day basis. Our findings suggest it is important to monitor and educate individuals with spinal cord injury/disease at the acute stage to improve medical outcomes. Caution is advised in the interpretation of these results as they were obtained in a small non-random sample using self-report data. Peer mentors play an increasingly important role in nurse-delivered education in the spinal cord injury/disease population. © 2011

  19. 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

  20. Congenital Zika Virus Infection Induces Severe Spinal Cord Injury.

    PubMed

    Ramalho, Fernando S; Yamamoto, Aparecida Y; da Silva, Luis L; Figueiredo, Luiz T M; Rocha, Lenaldo B; Neder, Luciano; Teixeira, Sara R; Apolinário, Letícia A; Ramalho, Leandra N Z; Silva, Deisy M; Coutinho, Conrado M; Melli, Patrícia P; Augusto, Marlei J; Santoro, Ligia B; Duarte, Geraldo; Mussi-Pinhata, Marisa M

    2017-08-15

    We report 2 fatal cases of congenital Zika virus (ZIKV) infection. Brain anomalies, including atrophy of the cerebral cortex and brainstem, and cerebellar aplasia were observed. The spinal cord showed architectural distortion, severe neuronal loss, and microcalcifications. The ZIKV proteins and flavivirus-like particles were detected in cytoplasm of spinal neurons, and spinal cord samples were positive for ZIKV RNA. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

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

    PubMed

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

    2017-03-15

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

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. Spinal cord electrophysiology II: extracellular suction electrode fabrication.

    PubMed

    Garudadri, Suresh; Gallarda, Benjamin; Pfaff, Samuel; Alaynick, William

    2011-02-20

    Development of neural circuitries and locomotion can be studied using neonatal rodent spinal cord central pattern generator (CPG) behavior. We demonstrate a method to fabricate suction electrodes that are used to examine CPG activity, or fictive locomotion, in dissected rodent spinal cords. The rodent spinal cords are placed in artificial cerebrospinal fluid and the ventral roots are drawn into the suction electrode. The electrode is constructed by modifying a commercially available suction electrode. A heavier silver wire is used instead of the standard wire given by the commercially available electrode. The glass tip on the commercial electrode is replaced with a plastic tip for increased durability. We prepare hand drawn electrodes and electrodes made from specific sizes of tubing, allowing consistency and reproducibility. Data is collected using an amplifier and neurogram acquisition software. Recordings are performed on an air table within a Faraday cage to prevent mechanical and electrical interference, respectively.

  7. 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

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

    PubMed

    Rouleau, Pascal; Guertin, Pierre A

    2013-01-01

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

  9. Biciliated ependymal cell proliferation contributes to spinal cord growth

    PubMed Central

    Alfaro-Cervello, Clara; Soriano-Navarro, Mario; Mirzadeh, Zaman; Alvarez-Buylla, Arturo; Garcia-Verdugo, Jose Manuel

    2013-01-01

    Two neurogenic regions have been described in the adult brain, the lateral ventricle subventricular zone and the dentate gyrus subgranular zone. It has been suggested that neural stem cells also line the central canal of the adult spinal cord. Using transmission and scanning electron microscopy and immunostaining, we describe here the organization and cell types of the central canal epithelium in adult mice. The identity of dividing cells was determined by three-dimensional ultrastructural reconstructions of [3H]thymidine-labeled cells and confocal analysis of bromodeoxyuridine labeling. The most common cell type lining the central canal had two long motile (9+2) cilia and was vimentin+, CD24+, FoxJ1+, Sox2+ and CD133+, but nestin- and glial fibrillary acidic protein (GFAP)-. These biciliated ependymal cells of the central canal (Ecc) resembled E2 cells of the lateral ventricles, but their basal bodies were different from that of E2 or E1 cells. Interestingly, we frequently found Ecc cells with two nuclei and four cilia, suggesting they are formed by incomplete cytokinesis or cell fusion. GFAP+ astrocytes with a single cilium and an orthogonally oriented centriole were also observed. The majority of dividing cells corresponded to biciliated Ecc cells. Central canal proliferation was most common during the active period of spinal cord growth. Pairs of labeled Ecc cells were observed within the central canal in adult mice 2.5 weeks post-labeling. Our work suggests that the vast majority of postnatal dividing cells in the central canal are Ecc cells and their proliferation is associated with the growth of the spinal cord. PMID:22434575

  10. 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.

  11. Cannabis use in persons with traumatic spinal cord injury in Denmark.

    PubMed

    Andresen, Sven R; Biering-Sørensen, Fin; Hagen, Ellen Merete; Nielsen, Jørgen F; Bach, Flemming W; Finnerup, Nanna B

    2017-01-31

    To evaluate recreational and medical cannabis use in individuals with traumatic spinal cord injury, including reasons and predictors for use, perceived benefits and negative consequences. Cross-sectional survey in Denmark. A 35-item questionnaire was sent to 1,101 patients with spinal cord injury who had been in contact with a rehabilitation centre between 1990 and 2012. A total of 537 participants completed the questionnaire. Of these, 36% had tried cannabis at least once and 9% were current users. Of current users, 79% had started to use cannabis before their spinal cord injury. The main reason for use was pleasure, but 65% used cannabis partly for spinal cord injury-related consequences and 59% reported at least good effect on pain and spasticity. Negative consequences of use were primarily inertia and feeling quiet/subdued. Lower age, living in rural areas/larger cities, tobacco-smoking, high alcohol intake and higher muscle stiffness were significantly associated with cannabis use. Those who had never tried cannabis reported that they would mainly use cannabis to alleviate pain and spasticity if it were legalized. Cannabis use is more frequent among individuals with spinal cord injury in Denmark than among the general population. High muscle stiffness and various demographic characteristics (lower age, living in rural areas/larger cities, tobacco-smoking and high alcohol intake) were associated with cannabis use. Most participants had started using cannabis before their spinal cord injury. There was considerable overlap between recreational and disability-related use.

  12. Chronic spinal cord injury in the cervical spine of a young soccer player.

    PubMed

    Kato, Yoshihiko; Koga, Michiaki; Taguchi, Toshihiko

    2010-05-12

    A 17-year-old male soccer player presented with numbness in the upper- and lower-left extremities of 6 months' duration. He had no apparent history of trauma but experienced neck pain during heading of the ball 5 years prior. A high-signal intensity area was seen on T2-weighted magnetic resonance imaging (MRI) of the cervical spine. No muscle weakness was observed. Hypoesthesia was observed in bilateral forearms, hands, and extremities below the inguinal region. Plain radiographs in the neutral position showed local kyphosis at C3/4. A small protrusion of the C3/4 disk was observed on T1-weighted MRI. A high-signal area in the spinal cord at the C3/4 level was observed on T2-weighted MRI, but this was not enhanced by gadolinium. Multiple sclerosis, intramedullary spinal cord tumor, sarcoidosis and malignant lymphoma, and spinal cord injury were all considered in the differential diagnosis. However, in view of the clinical, laboratory, and radiological investigations, we concluded that repeated impacts to the neck caused by heading of the ball during soccer induced a chronic, minor spinal cord injury. This contributed to the high-signal intensity change of the spinal cord in T2-weighted MRI. The present case demonstrates that repeated impact may cause chronic spinal cord injury. Soccer, American football, or rugby players presenting with neck or extremity symptoms should not be overlooked for the possibility of latent spinal cord injury, as this could present later development of more severe or unrecoverable spinal cord injuries. Copyright 2010, SLACK Incorporated.

  13. 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.

  14. 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.

  15. 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

  16. Methylene Blue Mitigates Acute Neuroinflammation after Spinal Cord Injury through Inhibiting NLRP3 Inflammasome Activation in Microglia

    PubMed Central

    Lin, Zhi-Hang; Wang, Si-Yuan; Chen, Li-Li; Zhuang, Jia-Yuan; Ke, Qing-Feng; Xiao, Dan-Rui; Lin, Wen-Ping

    2017-01-01

    The spinal cord injury (SCI) is a detrimental neurological disease involving the primary mechanical injury and secondary inflammatory damage. Curtailing the detrimental neuroinflammation would be beneficial for spinal cord function recovery. Microglia reside in the spinal cord and actively participate in the onset, progression and perhaps resolution of post-SCI neuroinflammation. In the current study, we tested the effects of methylene blue on microglia both in vitro and in a rat SCI model. We found that methylene blue inhibited the protein levels of IL-1β and IL-18 rather than their mRNA levels in activated microglia. Further investigation indicated that methylene blue deceased the activation of NLRP3 inflammasome and NLRC4 inflammasome in microglia in vitro. Moreover, in the rat SCI model, the similar effect of methylene blue on post-SCI microglia was also observed, except that the activation of NLRC4 inflammasome was not seen. The inhibition of microglia NLRP3 inflammasome was associated with down-regulation of intracellular reactive oxygen species (ROS). The administration of methylene blue mitigated the overall post-SCI neuroinflammation, demonstrated by decreased pro-inflammatory cytokine production and leukocyte infiltrates. Consequently, the neuronal apoptosis was partially inhibited and the hind limb locomotor function was ameliorated by methylene blue treatment. Our research highlights the role of methylene blue in inhibiting post-SCI neuroinflammation, and suggests that methylene blue might be used for SCI therapy. PMID:29311826

  17. Phrenic motoneuron expression of serotonergic and glutamatergic receptors following upper cervical spinal cord injury

    PubMed Central

    Mantilla, Carlos B.; Bailey, Jeffrey P.; Zhan, Wen-Zhi; Sieck, Gary C.

    2012-01-01

    Following cervical spinal cord injury at C2 (SH hemisection model) there is progressive recovery of phrenic activity. Neuroplasticity in the postsynaptic expression of neurotransmitter receptors may contribute to functional recovery. Phrenic motoneurons express multiple serotonergic (5-HTR) and glutamatergic (GluR) receptors, but the timing and possible role of these different neurotransmitter receptor subtypes in the neuroplasticity following SH are not clear. The current study was designed to test the hypothesis that there is an increased expression of serotonergic and glutamatergic neurotransmitter receptors within phrenic motoneurons after SH. In adult male rats, phrenic motoneurons were labeled retrogradely by intrapleural injection of Alexa 488-conjugated cholera toxin B. In thin (10 μm) frozen sections of the spinal cord, fluorescently-labeled phrenic motoneurons were visualized for laser capture microdissection (LCM). Using quantitative real-time RT-PCR in LCM samples, the time course of changes in 5-HTR and GluR mRNA expression was determined in phrenic motoneurons up to 21 days post-SH. Expression of 5-HTR subtypes 1b, 2a and 2c and GluR subtypes AMPA, NMDA, mGluR1 and mGluR5 was evident in phrenic motoneurons from control and SH rats. Phrenic motoneuron expression of 5-HTR2a increased ~8-fold (relative to control) at 14 days post-SH, whereas NMDA expression increased ~16-fold by 21-days post-SH. There were no other significant changes in receptor expression at any time post-SH. This is the first study to systematically document changes in motoneuron expression of multiple neurotransmitter receptors involved in regulation of motoneuron excitability. By providing information on the neuroplasticity of receptors expressed in a motoneuron pool that is inactivated by a higher-level spinal cord injury, appropriate pharmacological targets can be identified to alter motoneuron excitability. PMID:22227062

  18. 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.

  19. Widespread spinal cord involvement in progressive supranuclear palsy.

    PubMed

    Iwasaki, Yasushi; Yoshida, Mari; Hashizume, Yoshio; Hattori, Manabu; Aiba, Ikuko; Sobue, Gen

    2007-08-01

    We describe the histopathologic features of spinal cord lesions in 10 cases of progressive supranuclear palsy (PSP) and review the literature. Histologic examination revealed atrophy with myelin pallor in the anterior funiculus and anterolateral funiculus in the cervical and thoracic segments in eight of the 10 cases, whereas the posterior funiculus was well preserved. The degrees of atrophy of the anterior funiculus and the anterolateral funiculus correlated with that of the tegmentum of the medulla oblongata. Myelin pallor of the lateral corticospinal tract was observed in two of the 10 cases. Microscopic observation of the spinal white matter, particularly the cervical segment, revealed a few to several neuropil threads, particularly in the white matter surrounding the anterior horn after Gallyas-Braak (GB) staining or AT-8 tau immunostaining. However, the posterior funiculus was completely preserved from the presence of argyrophilic or tau-positive structures. In the spinal gray matter, widespread distribution of neurons with cytoplasmic inclusions and neuropil threads was observed, particularly in the medial division of the anterior horn and intermediate gray matter, especially in the cervical segment. Globose-type neurofibrillary tangles and pretangles were found. The distribution of GB- or AT-8 tau-positive small neurons and neuropil threads resembled that of the spinal interneurons. In conclusion, the spinal cord, especially the cervical segment, is constantly involved in the pathologic process of PSP. We speculate that spinal interneurons and their neuronal processes, particularly in the medial division of the anterior horn and intermediate gray matter of the cervical segment, are most severely damaged in the PSP spinal cord.

  20. Spinal Cord Electrophysiology II: Extracellular Suction Electrode Fabrication

    PubMed Central

    Garudadri, Suresh; Gallarda, Benjamin; Pfaff, Samuel; Alaynick, William

    2011-01-01

    Development of neural circuitries and locomotion can be studied using neonatal rodent spinal cord central pattern generator (CPG) behavior. We demonstrate a method to fabricate suction electrodes that are used to examine CPG activity, or fictive locomotion, in dissected rodent spinal cords. The rodent spinal cords are placed in artificial cerebrospinal fluid and the ventral roots are drawn into the suction electrode. The electrode is constructed by modifying a commercially available suction electrode. A heavier silver wire is used instead of the standard wire given by the commercially available electrode. The glass tip on the commercial electrode is replaced with a plastic tip for increased durability. We prepare hand drawn electrodes and electrodes made from specific sizes of tubing, allowing consistency and reproducibility. Data is collected using an amplifier and neurogram acquisition software. Recordings are performed on an air table within a Faraday cage to prevent mechanical and electrical interference, respectively. PMID:21372792

  1. 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. Morphology of the caudal spinal cord in Rana (Ranidae) and Xenopus (Pipidae) tadpoles.

    PubMed

    Nishikawa, K; Wassersug, R

    1988-03-08

    Using a variety of neuroanatomical and histological techniques, we compare the spinal cord and peripheral nerve distribution in the tails of larvae from Xenopus laevis and three species of Rana. The relatively large, postsacral spinal cord of Xenopus contains abundant motoneurons and their axons. Spinal nerves exit from the spinal cord in a regular array, one nerve per myotome, from the cervical region to near the end of the tail. Somata of motoneurons innervating caudal myotomes are found along the entire length of the tail. In contrast, the caudal cord of Rana is reduced to a filum terminale consisting of little more than an ependymal tube; spinal nerves to all caudal myotomes leave the cord in the sacral region and reach their motor targets via a cauda equina and caudal plexus. Motoneuron cell bodies innervating caudal myotomes are found only in the sacral region. The Rana larval pattern is similar to that of adult frogs and mammals, whereas the Xenopus larval pattern is more like that of salamanders and reptiles. These gross neuroanatomical differences are not due to differences in the size or developmental stage of the tadpoles, but instead are associated with differences in the swimming behavior of the larvae. The presence of motoneurons in the caudal spinal cord of Xenopus may provide local intermyotomal control within the tail; the elongated topography of the cord appears to permit finer, rostral-to-caudal regulation of neuromuscular activity. The Rana spinal cord, on the other hand--with motoneurons clustered anteriorly--may produce concurrent firing of adjacent ipsilateral myotomes, but at the expense of fine intermyotomal regulation. The fact that nerves in the tail of Xenopus enter and exit from the spinal cord locally, as opposed to far anteriorly as in Rana, means that for tadpoles of the same size, reflex arc lengths are many times shorter in Xenopus.

  3. Dynamic Detection of Spinal Cord Position During Postural Changes Using Near-Infrared Reflectometry.

    PubMed

    Wolf, Erich W

    2015-08-01

    Motion of the spinal cord relative to a spinal cord stimulator epidural electrode array can cause suboptimal stimulation: either noxious, inefficient, or insufficient. Adaptive stimulation attempts to mitigate these effects by modulating stimulation parameters in a position-dependent fashion. Near-infrared (NIR) reflectometry is demonstrated to provide real-time direct measurement of spinal cord position at the site of stimulation, which can facilitate closed-loop adaptive stimulation during static and dynamic motion states. A miniature sensor array consisting of an NIR light emitting diode flanked by phototransistors potted in epoxy was placed in the dorsal epidural space of a human cadaver at the T8 level via laminotomy. Turgor of the subarachnoid space was maintained by intrathecal infusion of saline. NIR reflectance was measured as the cadaver was rotated about its longitudinal axis on a gantry. NIR reflectance was correlated with gantry position and velocity. NIR reflectometry suggests gravitational force is the primary determinant of cord position in static, ordinal positions. Under dynamic motion conditions, there was statistically significant cross-correlation between reflectometry data and the tangential velocity squared, suggesting that centripetal force was the primary determinant of cord position as the gantry was rotated. Reflectometry data strongly correlated with a simple geometric model of anticipated spinal cord precession within the spinal canal. Spinal cord position during dynamic motion has been shown to differ from static predictions due to additional influences such as centripetal force. These findings underscore limitations in extrapolating spinal cord position from surrogates such as body position or body acceleration at sites remote from the stimulating electrodes. NIR reflectometry offers a real-time direct measure of spinal cord position in both static and dynamic motion states, which may facilitate closed-loop adaptive stimulation

  4. [Curcumin down-regulates CX3CR1 expression in spinal cord dorsal horn and DRG in neuropathic pain rats].

    PubMed

    Zheng, Jinwei; Zheng, Changjian; Cao, Hong; Li, Jun; Lian, Qingquan

    2011-09-01

    To investigate the effects of curcumin on the behavior of chronic constrictive injury (CCI) rats and the CX3CR1 expression in spinal cord dorsal horn and dorsal root ganglia (DRG). Seventy-two male SD rats were randomly divided into 4 groups: 1) Sham operation group (Sham); 2) Chronic constrictive injury group (CCI); 3) Curcumin treated group (Cur), administrated with curcumin 100 mg x kg(-1) x d(-1) ip for 14 days after CCI; 4) Solvent contrast group (SC), administrated with an equal volume of solvent for 14 days after CCI. Paw thermal withdrawal (PTWL) and paw mechanical withdrawal threshold (PMWT) were measured on 2 pre-operative and 1, 3, 5, 7, 10, 14 post-operative days respectively. The lumbar segments L4-5 of the spinal cord and the L4, L5 DRG were removed at 3, 7, 14 days after surgery. The expression of CX3CR1 was determined by immunohistochemical staining. Compared with Sham group, PTWL and PMWT in CCI group were significantly lower on each post-operative day (P<0.01), which reached a nadir on the 3rd day after CCI (PTWL was 6.5 +/- 1.1, PMWT was 22.6 +/- 5.1), and the expression of CX3CR1 were markedly increased in spinal cord dorsal horn and DRG. In Cur group, PTWL were higher than in CCI group on 7, 10, 14 post-operative day (P<0.05), and PMWT were higher than those in CCI group on 10 and 14 post-operative day (P<0.05). The administration of curcumin could significantly attenuate the activation of CX3CR1 induced by CCI. The study suggests that curcumin ameliorates the CCI-induced neuropathic pain, probably by attenuating the expression of CX3CR1 in spinal cord dorsal horn and dorsal root ganglia.

  5. "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.

  6. Reliable and fast volumetry of the lumbar spinal cord using cord image analyser (Cordial).

    PubMed

    Tsagkas, Charidimos; Altermatt, Anna; Bonati, Ulrike; Pezold, Simon; Reinhard, Julia; Amann, Michael; Cattin, Philippe; Wuerfel, Jens; Fischer, Dirk; Parmar, Katrin; Fischmann, Arne

    2018-04-30

    To validate the precision and accuracy of the semi-automated cord image analyser (Cordial) for lumbar spinal cord (SC) volumetry in 3D T1w MRI data of healthy controls (HC). 40 3D T1w images of 10 HC (w/m: 6/4; age range: 18-41 years) were acquired at one 3T-scanner in two MRI sessions (time interval 14.9±6.1 days). Each subject was scanned twice per session, allowing determination of test-retest reliability both in back-to-back (intra-session) and scan-rescan images (inter-session). Cordial was applied for lumbar cord segmentation twice per image by two raters, allowing for assessment of intra- and inter-rater reliability, and compared to a manual gold standard. While manually segmented volumes were larger (mean: 2028±245 mm 3 vs. Cordial: 1636±300 mm 3 , p<0.001), accuracy assessments between manually and semi-automatically segmented images showed a mean Dice-coefficient of 0.88±0.05. Calculation of within-subject coefficients of variation (COV) demonstrated high intra-session (1.22-1.86%), inter-session (1.26-1.84%), as well as intra-rater (1.73-1.83%) reproducibility. No significant difference was shown between intra- and inter-session reproducibility or between intra-rater reliabilities. Although inter-rater reproducibility (COV: 2.87%) was slightly lower compared to all other reproducibility measures, between rater consistency was very strong (intraclass correlation coefficient: 0.974). While under-estimating the lumbar SCV, Cordial still provides excellent inter- and intra-session reproducibility showing high potential for application in longitudinal trials. • Lumbar spinal cord segmentation using the semi-automated cord image analyser (Cordial) is feasible. • Lumbar spinal cord is 40-mm cord segment 60 mm above conus medullaris. • Cordial provides excellent inter- and intra-session reproducibility in lumbar spinal cord region. • Cordial shows high potential for application in longitudinal trials.

  7. 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

  8. Refractory orthostatic hypotension in a patient with a spinal cord injury: Treatment with droxidopa.

    PubMed

    Canosa-Hermida, Eva; Mondelo-García, Cristina; Ferreiro-Velasco, María Elena; Salvador-de la Barrera, Sebastián; Montoto-Marqués, Antonio; Rodríguez-Sotillo, Antonio; Vizoso-Hermida, José Ramón

    2018-01-01

    Orthostatic hypotension (OH) is a common complication in patients with a spinal cord injury, mainly affecting complete injuries above neurological level T6. It is generally more severe during the acute phase but can remain symptomatic for several years. A 65-year-old male with a grade ASIA A post-traumatic cervical spinal cord injury, at neurological level C4, presenting with symptomatic refractory OH. Increased blood pressure (BP) levels and an overall clinical improvement was observed after administering an increasing dose of droxidopa. Treatment was started at a dose of 100 mg twice daily (bid), one to be taken upon rising in the morning and another one in the afternoon, at least three hours before bedtime. According to the patient's symptomatic response, each individual dose was increased by 100 mg at 48-hour intervals. Both increased mean BP levels and a subjective symptomatic improvement were evidenced at a dose of 300 mg bid. Treatment with droxidopa increases BP levels and improves symptoms related to refractory OH using all physical and pharmacological measures available. It could therefore constitute an effective alternative treatment for OH in patients with a spinal cord injury.

  9. 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.

  10. Clinical interpretation of the Spinal Cord Injury Functional Index (SCI-FI).

    PubMed

    Fyffe, Denise; Kalpakjian, Claire Z; Slavin, Mary; Kisala, Pamela; Ni, Pengsheng; Kirshblum, Steven C; Tulsky, David S; Jette, Alan M

    2016-09-01

    To provide validation of functional ability levels for the Spinal Cord Injury - Functional Index (SCI-FI). Cross-sectional. Inpatient rehabilitation hospital and community settings. A sample of 855 individuals with traumatic spinal cord injury enrolled in 6 rehabilitation centers participating in the National Spinal Cord Injury Model Systems Network. Not Applicable. Spinal Cord Injury-Functional Index (SCI-FI). Cluster analyses identified three distinct groups that represent low, mid-range and high SCI-FI functional ability levels. Comparison of clusters on personal and other injury characteristics suggested some significant differences between groups. These results strongly support the use of SCI-FI functional ability levels to document the perceived functional abilities of persons with SCI. Results of the cluster analysis suggest that the SCI-FI functional ability levels capture function by injury characteristics. Clinical implications regarding tracking functional activity trajectories during follow-up visits are discussed.

  11. 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

  12. Focal thoracolumbar spinal cord lymphosarcoma in a ferret (Mustela putorius furo)

    PubMed Central

    Ingrao, Joelle C.; Eshar, David; Vince, Andrew; Lee-Chow, Bridget; Nykamp, Stephanie; DeLay, Josepha; Smith, Dale

    2014-01-01

    A 6-year-old, castrated male domestic ferret (Mustela putorius furo) was euthanized following progressive hind limb paresis and atonia of the bladder of 1-year duration. Neurological evaluation localized the lesion to the thoracolumbar spinal region, and magnetic resonance imaging showed a focal intramedullary spinal cord lesion. Histopathology revealed an extensive, unencapsulated, poorly demarcated mass within the thoracolumbar spinal cord, diagnosed as lymphosarcoma. PMID:24982519

  13. Receptor activated bladder and spinal ATP release in neurally intact and chronic spinal cord injured rats

    PubMed Central

    Salas, Nilson A.; Somogyi, George T.; Gangitano, David A.; Boone, Timothy B.; Smith, Christopher P.

    2009-01-01

    Neurally intact (NI) rats and chronic spinal cord injured (SCI) rats were studied to determine how activation of mechanosensory or cholinergic receptors in the bladder urothelium evokes ATP release from afferent terminals in the bladder as well as in the spinal cord. Spinal cord transection was performed at the T9-T10 level 2–3 weeks prior to the experiment and a microdialysis fiber was inserted in the L6-S1 lumbosacral spinal cord. Mechanically evoked (i.e. 10cm/w bladder pressure) ATP release into the bladder lumen was approximately 6.5 fold higher in SCI compared to NI rats (p<0.05). Intravesical carbachol (CCh) induced a significantly greater release of ATP in the bladder from SCI as compared to NI rats (3424.32 ± 1255.57 vs. 613.74 ± 470.44 pmol/ml, respectively, p<0.05). However, ATP release in NI or SCI rats to intravesical CCh was not affected by the muscarinic antagonist atropine (Atr). Spinal release of ATP to bladder stimulation with 10cm/w pressure was 5-fold higher in SCI compared to NI rats (p<0.05). CCh also induced a significantly greater release of spinal ATP in SCI rats compared to controls (4.3 ± 0.9 vs. 0.90 ± 0.15 pmol, p < 0.05). Surprisingly, the percent inhibitory effect of Atr on CCh-induced ATP release was significantly less in SCI as compared to NI rats (49% vs. 89%, respectively). SCI induces a dramatic increase in intravesical pressure and cholinergic receptor evoked bladder and spinal ATP release. Muscarinic receptors do not mediate intravesical CCh induced ATP release into the bladder lumen in NI or SCI rats. In NI rats sensory muscarinic receptors are the predominant mechanism by which CCh induces ATP release from primary afferents within the lumbosacral spinal cord. Following SCI, however, nicotinic or purinergic receptor mechanisms become active, as evidenced by the fact that Atr was only partially effective in inhibiting CCh-induced spinal ATP release. PMID:17067723

  14. 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.

  15. [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.

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

    PubMed

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

    2018-03-01

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

  17. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  19. 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

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

    PubMed

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

    2014-03-01

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

  1. 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).

  2. Complete segmental resection of the spine, including the spinal cord, for telangiectatic osteosarcoma: a report of 2 cases.

    PubMed

    Murakami, Hideki; Tomita, Katsuro; Kawahara, Norio; Oda, Makoto; Yahata, Tetsutaro; Yamaguchi, Takehiko

    2006-02-15

    Two case reports of telangiectatic osteosarcoma treated with complete segmental resection of the spine, including the spinal cord. To report the en bloc tumor excision, including the spinal cord, for telangiectatic osteosarcoma, and discuss the indication of cord transection and influence after cutting the spinal cord. To our knowledge, there are no previous reports describing telangiectatic osteosarcoma of the spine and the subsequent en bloc excision of the spine, including the spinal cord. The clinical and radiographic presentations of 2 cases with telangiectatic osteosarcoma are presented. Because these 2 cases already had complete paralysis for at least 1 month, it was suspected that there was no possibility of recovering spinal cord function. Complete segmental spinal resection (total en bloc spondylectomy) was performed. At that level, the spinal cord was also cut and resected. En bloc excision of the tumor with a wide margin was achieved in both cases. In the resected specimen, the nerve cells in the spinal cord had lapsed into degenerative necrosis. The pathologic findings showed that there was no hope for recovery of spinal cord function. En bloc spinal resection, including the spinal cord, is an operation allowed when there is no hope for recovery of spinal cord function. This surgery should be accepted as an option in spine tumor surgeries.

  3. Spinal cord compression in pseudohypoparathyroidism.

    PubMed

    Roberts, Timothy T; Khasnavis, Siddharth; Papaliodis, Dean N; Citone, Isabella; Carl, Allen L

    2013-12-01

    Spinal cord compression associated with pseudohypoparathyroidism (PHP) is an increasingly reported sequelae of the underlying metabolic syndrome. The association of neurologic dysfunction with PHP is not well appreciated. We believe this to be secondary to a combination of underlying congenital stenosis, manifest by short pedicles secondary to premature physeal closure, and hypertrophic ossification of the vertebral bony and ligamentous complexes. The purpose of this case report is to review the case of spinal stenosis in a child with PHP Type Ia. We are aware of only eight published reports of patients with PHP Type Ia and spinal stenosis-there are only two previously known cases of pediatric spinal stenosis secondary to PHP. This is a case report detailing the symptoms, diagnosis, interventions, complications, and ultimate outcomes of a pediatric patient undergoing spinal decompression and fusion for symptomatic stenosis secondary to PHP Type Ia. Literature search was reviewed regarding the reports of spinal stenosis and PHP, and the results are culminated and discussed. We report on a 14-year-old obese male with PHP and progressive lower extremity weakness secondary to congenital spinal stenosis. Examination revealed functional upper extremities with spastic paraplegia of bilateral lower extremities. The patient's neurologic function was cautiously monitored, but he deteriorated to a bed-bound state, preoperatively. The patient's chart was reviewed, summarized, and presented. Literature was searched using cross-reference of PHP and the terms "spinal stenosis," "myelopathy", "myelopathic," and "spinal cord compression." All relevant case reports were reviewed, and the results are discussed herein. The patient underwent decompression and instrumented fusion of T2-T11. He improved significantly with regard to lower extremity function, achieving unassisted ambulation function after extensive rehabilitation. Results from surgical decompression in previously reported

  4. Percutaneous Radiofrequency Ablation of Painful Spinal Tumors Adjacent to the Spinal Cord with Real-Time Monitoring of Spinal Canal Temperature: A Prospective Study

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

    Nakatsuka, Atsuhiro, E-mail: nakatuka@clin.medic.mie-u.ac.jp; Yamakado, Koichiro; Takaki, Haruyuki

    2009-01-15

    PurposeTo prospectively evaluate the feasibility, safety, and clinical utility of bone radiofrequency (RF) ablation with real-time monitoring of the spinal canal temperature for the treatment of spinal tumors adjacent to the spinal cord.Materials and MethodsOur Institutional Review Board approved this study. Patients gave informed consent. The inclusion criteria were (a) a painful spinal metastasis and (b) a distance of 1 cm or less between the metastasis and the spinal cord. The thermocouple was placed in the spinal canal under CT fluoroscopic guidance. When the spinal canal temperature reached 45{sup o}C, RF application was immediately stopped. RF ablation was considered technicallymore » successful when the procedure was performed without major complications. Clinical success was defined as a fall in the visual analogue scale score of at least 2 points.ResultsTen patients with spinal tumors measuring 3-8 cm (mean, 4.9 {+-} 1.5 cm) were enrolled. The distance between the tumor and the spinal cord was 1-6 mm (mean, 2.4 {+-} 1.6 mm). All procedures were judged technically successful (100%). The spinal canal temperature did not exceed 45{sup o}C in 9 of the 10 patients (90%). In the remaining patient, the temperature rose to 48{sup o}C, resulting in transient neural damage, although RF application was immediately stopped when the temperature reached 45{sup o}C. Clinical success was achieved within 1 week in all patients (100%).ConclusionBone RF ablation with real-time monitoring of the spinal canal temperature is feasible, safe, and clinically useful for the treatment of painful spinal metastases adjacent to the spinal cord.« less

  5. 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

  6. 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

  7. Post-traumatic syringomyelia: CSF hydrodynamic changes following spinal cord injury are the driving force in the development of PTSM.

    PubMed

    Shields, Christopher B; Zhang, Yi Ping; Shields, Lisa B E

    2012-01-01

    Post-traumatic syringomyelia (PTSM) is a disorder that occurs infrequently following spinal cord injury (SCI), characterized by progressive neurological deterioration resulting from syrinx expansion originating in proximity to the traumatic epicenter. Several pathogenetic factors are associated with this disorder, however, the precise mechanism of the development of PTSM is controversial. Combined anatomical alterations and molecular changes following trauma to the spinal cord and arachnoid participate in the development of this condition. These factors include narrowing or obstruction of the subarachnoid space (SAS), central canal occlusion, myelomalacia, and alterations in intramedullary water permeability. If a patient sustains a SCI with delayed progressive deterioration in neurological function, in association with the MRI appearance of syringomyelia (SM), the diagnosis of PTSM is straightforward. The treatment of PTSM has not undergone any significant changes recently. The surgical treatment of PTSM consists of reconstructing the SAS or shunting fluid away from the syrinx to other locations. The advantages and disadvantages of each procedure will be discussed. With greater understanding of the mechanisms contributing to the development of SM, including advanced diagnostic methods and further advances in the development of artificial dural and shunting tubing, future therapies of PTSM will be more effective and long-lasting. Incorporation of alterations of AQP4 expression provides an intriguing possibility for future treatment of PTSM. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Boomerang deformity of cervical spinal cord migrating between split laminae after laminoplasty.

    PubMed

    Kimura, S; Gomibuchi, F; Shimoda, H; Ikezawa, Y; Segawa, H; Kaneko, F; Uchiyama, S; Homma, T

    2000-04-01

    Patients with cervical compression myelopathy were studied to elucidate the mechanism underlying boomerang deformity, which results from the migration of the cervical spinal cord between split laminae after laminoplasty with median splitting of the spinous processes (boomerang sign). Thirty-nine cases, comprising 25 patients with cervical spondylotic myelopathy, 8 patients with ossification of the posterior longitudinal ligament, and 6 patients with cervical disc herniation with developmental canal stenosis, were examined. The clinical and radiological findings were retrospectively compared between patients with (B group, 8 cases) and without (C group, 31 cases) boomerang sign. Moderate increase of the grade of this deformity resulted in no clinical recovery, although there was no difference in clinical recovery between the two groups. Most boomerang signs developed at the C4/5 and/or C5/6 level, where maximal posterior movement of the spinal cord was achieved. Widths between lateral hinges and between split laminae in the B group were smaller than in the C group. Flatness of the spinal cord in the B group was more severe than in the C group. In conclusion, the boomerang sign was caused by posterior movement of the spinal cord, narrower enlargement of the spinal canal and flatness of the spinal cord.

  9. Experiences of Living with Pain after a Spinal Cord Injury

    DTIC Science & Technology

    2013-09-01

    AD_________________ Award Number: W81XWH-12-1-0465 TITLE: Experiences of Living with Pain after a...COVERED 01 September 2012 – 31 August 2013 4. TITLE AND SUBTITLE Experiences of Living with Pain after a Spinal Cord Injury 5a. CONTRACT NUMBER...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Persistent chronic pain is prevalent after a spinal cord injury (SCI), with

  10. 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.

  11. 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.

  12. Folic Acid Modulates Matrix Metalloproteinase-2 Expression, Alleviates Neuropathic Pain, and Improves Functional Recovery in Spinal Cord-Injured Rats

    PubMed Central

    Miranpuri, Gurwattan S.; Meethal, Sivan Vadakkadath; Sampene, Emmanuel; Chopra, Abhishek; Buttar, Seah; Nacht, Carrie; Moreno, Neydis; Patel, Kush; Liu, Lisa; Singh, Anupama; Singh, Chandra K.; Hariharan, Nithya; Iskandar, Bermans; Resnick, Daniel K.

    2017-01-01

    Background The molecular underpinnings of spinal cord injury (SCI) associated with neuropathic pain (NP) are unknown. Recent studies have demonstrated that matrix metalloproteinases (MMPs) such as MMP2 play a critical role in inducing NP following SCI. Promoter methylation of MMPs is known to suppress their transcription and reduce NP. In this context, it has been shown in rodents that folic acid (FA), an FDA approved dietary supplement and key methyl donor in the central nervous system (CNS), increases axonal regeneration and repair of injured CNS in part via methylation. Purpose Based on above observations, in this study, we test whether FA could decrease MMP2 expression and thereby decrease SCI-induced NP. Methods Sprague-Dawley male rats weighing 250–270 g received contusion spinal cord injuries (cSCIs) with a custom spinal cord impactor device that drops a 10 g weight from a height of 12.5 mm. The injured rats received either i.p. injections of FA (80 µg/kg) or water (control) 3 days prior and 17 days post-cSCI (mid phase) or for 3 days pre-cSCI and 14 days post-cSCI ending on the 42nd day of cSCI (late phase). The functional neurological deficits due to cSCI were then assessed by Basso, Beattie, and Bresnahan (BBB) scores either on post-impaction days 0 through 18 post-cSCI (mid phase) or on days 0, 2, 7, 14, 21, 28, 35, and 42 (late phase). Baseline measurements were taken the day before starting treatments. Thermal hyperalgesia (TH) testing for pain was performed on 4 days pre-cSCI (baseline data) and on days 18, 21, 28, 35, and 42 post-cSCI. Following TH testing, animals were euthanized and spinal cords harvested for MMP-2 expression analysis. Result The FA-treated groups showed higher BBB scores during mid phase (day 18) and in late phase (day 42) of injury compared to controls, suggesting enhanced functional recovery. There is a transient decline in TH in animals from the FA-treated group compared to controls when tested on days 18, 21, 28, and 35

  13. Site-specific gene transfer into the rat spinal cord by photomechanical waves

    NASA Astrophysics Data System (ADS)

    Ando, Takahiro; Sato, Shunichi; Toyooka, Terushige; Uozumi, Yoichi; Nawashiro, Hiroshi; Ashida, Hiroshi; Obara, Minoru

    2011-10-01

    Nonviral, site-specific gene delivery to deep tissue is required for gene therapy of a spinal cord injury. However, an efficient method satisfying these requirements has not been established. This study demonstrates efficient and targeted gene transfer into the spinal cord by using photomechanical waves (PMWs), which were generated by irradiating a black laser absorbing rubber with 532-nm nanosecond Nd:YAG laser pulses. After a solution of plasmid DNA coding for enhanced green fluorescent protein (EGFP) or luciferase was intraparenchymally injected into the spinal cord, PMWs were applied to the target site. In the PMW application group, we observed significant EGFP gene expression in the white matter and remarkably high luciferase activity only in the spinal cord segment exposed to the PMWs. We also assessed hind limb movements 24 h after the application of PMWs based on the Basso-Beattie-Bresnahan (BBB) score to evaluate the noninvasiveness of this method. Locomotor evaluation showed no significant decrease in BBB score under optimum laser irradiation conditions. These findings demonstrated that exogenous genes can be efficiently and site-selectively delivered into the spinal cord by applying PMWs without significant locomotive damage.

  14. 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...

  15. One day of motor training with amphetamine impairs motor recovery following spinal cord injury.

    PubMed

    Wong, Jamie K; Steward, Oswald

    2012-02-01

    It has previously been reported that a single dose of amphetamine paired with training on a beam walking task can enhance locomotor recovery following brain injury (Feeney et al., 1982). Here, we investigated whether this same drug/training regimen could enhance functional recovery following either thoracic (T9) or cervical (C5) spinal cord injury. Different groups of female Sprague-Dawley rats were trained on a beam walking task, and in a straight alley for assessment of hindlimb locomotor recovery using the BBB locomotor scale. For rats that received C5 hemisections, forelimb grip strength was assessed using a grip strength meter. Three separate experiments assessed the consequences of training rats on the beam walking task 24 h following a thoracic lateral hemisection with administration of either amphetamine or saline. Beginning 1 h following drug administration, rats either received additional testing/retraining on the beam hourly for 6 h, or they were returned to their home cages without further testing/retraining. Rats with thoracic spinal cord injuries that received amphetamine in conjunction with testing/retraining on the beam at 1 day post injury (DPI) exhibited significantly impaired recovery on the beam walking task and BBB. Rats with cervical spinal cord injuries that received training with amphetamine also exhibited significant impairments in beam walking and locomotion, as well as impairments in gripping and reaching abilities. Even when administered at 14 DPI, the drug/training regimen significantly impaired reaching ability in cervical spinal cord injured rats. Impairments were not seen in rats that received amphetamine without training. Histological analyses revealed that rats that received training with amphetamine had significantly larger lesions than saline controls. These data indicate that an amphetamine/training regimen that improves recovery after cortical injury has the opposite effect of impairing recovery following spinal cord injury

  16. 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

  17. Breaking the News in Spinal Cord Injury

    PubMed Central

    Kirshblum, Steven; Fichtenbaum, Joyce

    2008-01-01

    Summary: Breaking the bad news in terms of prognosis for significant motor recovery following a neurologically complete spinal cord injury (SCI) is one of the most difficult tasks for the spinal cord medicine specialist. Learning the skills to facilitate this communication is extremely important to better assist patients to understand their prognosis as well as foster hope for their future. If bad news is delivered poorly it can cause confusion and long-lasting distress and resentment; if done well, it may assist understanding, adjustment, and acceptance. This article provides the physician who cares for patients with SCI with some concepts to consider when discussing prognosis with patients and their families. PMID:18533406

  18. Spinal Cord Injury—Past, Present, and Future

    PubMed Central

    Donovan, William H

    2007-01-01

    Summary: This special report traces the path of spinal cord injury (SCI) from ancient times through the present and provides an optimistic overview of promising clinical trials and avenues of basic research. The spinal cord injuries of Lord Admiral Sir Horatio Nelson, President James A. Garfield, and General George Patton provide an interesting perspective on the evolution of the standard of care for SCI. The author details the contributions of a wide spectrum of professionals in the United States, Europe, and Australia, as well as the roles of various government and professional organizations, legislation, and overall advances in surgery, anesthesia, trauma care, imaging, pharmacology, and infection control, in the advancement of care for the individual with SCI. PMID:17591221

  19. Spinal cord protection during radiation therapy

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

    Coia, L.; Chu, J.; Larsen, R.

    1986-09-01

    Treating intrathoracic malignancies to high doses, particularly those of lung and esophagus, requires limiting the radiation dose delivered to the spinal cord. Several factors are important in determining the cord dose. These are: The distance from the block or collimator edge to the cord, the variation of dose with distance from the block or collimator edge and, the expected variation of this distance for clinical set-up from day-to-day. When treating with an oblique beam, the position of the cord may be difficult to identify. A technique for localizing the spinal cord on a simulator film at an arbitrary gantry anglemore » is presented. The technique requires determination of distances from the central axis of the beam to the medial aspect of the pedicle and posterior vertebral body. These can readily be obtained from measurements on orthogonal, AP/PA and lateral isocentric simulator radiographs. A mathematical transformation is applied to determine the corresponding cord locations on the oblique radiographs for any arbitrary gantry angle. The accuracy of cord localization was within 2-3 mm with a precision of 2 mm for five physicians who used this technique. The beam edge characteristics for 60Co, 6 MV, and 10 MV teletherapy unit were measured for various depths and field sizes. For the 6 and 10 MV units, the beam penumbra is nearly independent of the field size, depth and field defining devices (inner and outer collimator jaws, trimmer bars, and shielding blocks). Because the beam penumbra is dependent on the design of the linear accelerator, its measurement should be made individually for each linear accelerator. Our preliminary data on patient positioning uncertainty did not exceed the 6-8 mm limit documented in the literature.« less

  20. Label-free imaging of rat spinal cords based on multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Liao, Chenxi; Wang, Zhenyu; Zhou, Linquan; Zhu, Xiaoqin; Liu, Wenge; Chen, Jianxin

    2016-10-01

    As an integral part of the central nervous system, the spinal cord is a communication cable between the body and the brain. It mainly contains neurons, glial cells, nerve fibers and fiber tracts. The recent development of the optical imaging technique allows high-resolution imaging of biological tissues with the great potential for non-invasively looking inside the body. In this work, we evaluate the imaging capacity of multiphoton microscopy (MPM) based on second harmonic generation (SHG) and two-photon excited fluorescence (TPEF) for the cells and extracellular matrix in the spinal cord at molecular level. Rat spinal cord tissues were sectioned and imaged by MPM to demonstrate that MPM is able to show the microstructure including white matter, gray matter, ventral horns, dorsal horns, and axons based on the distinct intrinsic sources in each region of spinal cord. In the high-resolution and high-contrast MPM images, the cell profile can be clearly identified as dark shadows caused by nuclei and encircled by cytoplasm. The nerve fibers in white matter region emitted both SHG and TPEF signals. The multiphoton microscopic imaging technique proves to be a fast and effective tool for label-free imaging spinal cord tissues, based on endogenous signals in biological tissue. It has the potential to extend this optical technique to clinical study, where the rapid and damage-free imaging is needed.

  1. A rare case of multifocal intramedullary germinoma in cervical spinal cord.

    PubMed

    Wang, R; Fan, X; Zhang, B

    2014-06-01

    Case report. We present for the first time a patient with multifocal intramedullary cervical spinal cord germ cell tumors with elevated serum alpha-fetoprotein (AFP). Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China. A 19-year-old girl experienced numbness in her right leg 10 months before diagnosis. The numbness gradually became severe and extended up to the thorax. Magnetic resonance imaging (MRI) visualized several intramedullary masses with intensive enhancement and extensive peritumoral edema in the spinal cord at the C3-T1 vertebral body levels. Administration of methylprednisolone caused no treatment effect. The largest mass, which was located at the T1 level inside the normal spinal cord and confirmed by naked eye observation, was completely extracted under a microscope. Postoperative pathological examination demonstrated the so-called 'two-cell pattern,' which is typical of germinoma with placental alkaline phosphatase expression. The serum level of AFP was 64.50 ng ml(-1) (normal range: 0-5 ng ml(-1)). The residual tumor was eliminated through radiation therapy (local 30 Gy) following surgery. Afterward, the patient's neurological deficits were improved but not resolved. Six years after surgery, no recurrence was encountered and the patient remained stable. Radiotherapy is the salvage therapy for spinal cord germinoma. Steroids were of no therapeutic value in the treatment of intramedullary spinal cord germinoma.

  2. Co-Ultramicronized Palmitoylethanolamide/Luteolin Promotes Neuronal Regeneration after Spinal Cord Injury

    PubMed Central

    Crupi, Rosalia; Impellizzeri, Daniela; Bruschetta, Giuseppe; Cordaro, Marika; Paterniti, Irene; Siracusa, Rosalba; Cuzzocrea, Salvatore; Esposito, Emanuela

    2016-01-01

    Spinal cord injury (SCI) stimulates activation of astrocytes and infiltration of immune cells at the lesion site; however, the mechanism that promotes the birth of new neurons is still under debate. Neuronal regeneration is restricted after spinal cord injury, but can be stimulated by experimental intervention. Previously we demonstrated that treatment co-ultramicronized palmitoylethanolamide and luteolin, namely co-ultraPEALut, reduced inflammation. The present study was designed to explore the neuroregenerative properties of co-ultraPEALut in an estabished murine model of SCI. A vascular clip was applied to the spinal cord dura at T5–T8 to provoke injury. Mice were treated with co-ultraPEALut (1 mg/kg, intraperitoneally) daily for 72 h after SCI. Co-ultraPEALut increased the numbers of both bromodeoxyuridine-positive nuclei and doublecortin-immunoreactive cells in the spinal cord of injured mice. To correlate neuronal development with synaptic plasticity a Golgi method was employed to analyze dendritic spine density. Co-ultraPEALut administration stimulated expression of the neurotrophic factors brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, nerve growth factor, and neurotrophin-3. These findings show a prominent effect of co-ultraPEALut administration in the management of survival and differentiation of new neurons and spine maturation, and may represent a therapeutic treatment for spinal cord and other traumatic diseases. PMID:27014061

  3. 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

  4. Spinal dural arteriovenous fistulas: the most frequent vascular malformations of the spinal cord.

    PubMed

    Iglesias Gordo, J; Martínez García, R

    Spinal dural arteriovenous fistulas are produced by direct communication between the arterial and venous systems of the spinal cord, causing hypertension in the latter with spinal cord dysfunction. It is a rare pathology with unknown etiology and non-specific clinical symptoms that usually results in a delayed diagnosis. Often radiologists are the first to guide the disease towards an adequate diagnosis. Characteristic findings can be seen through MR or MR angiography, and may even locate the fistula in a high percentage of cases, although the pathology must be confirmed by spinal angiography. There are two treatment modalities: endovascular and surgical therapy. Endovascular treatment has improved in recent years with the advantages of a less invasive approach and is therefore usually chosen as primary therapy. In this article we review the main clinical manifestations, imaging findings and treatment of this pathology. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. MRI Atlas-Based Measurement of Spinal Cord Injury Predicts Outcome in Acute Flaccid Myelitis.

    PubMed

    McCoy, D B; Talbott, J F; Wilson, Michael; Mamlouk, M D; Cohen-Adad, J; Wilson, Mark; Narvid, J

    2017-02-01

    Recent advances in spinal cord imaging analysis have led to the development of a robust anatomic template and atlas incorporated into an open-source platform referred to as the Spinal Cord Toolbox. Using the Spinal Cord Toolbox, we sought to correlate measures of GM, WM, and cross-sectional area pathology on T2 MR imaging with motor disability in patients with acute flaccid myelitis. Spinal cord imaging for 9 patients with acute flaccid myelitis was analyzed by using the Spinal Cord Toolbox. A semiautomated pipeline using the Spinal Cord Toolbox measured lesion involvement in GM, WM, and total spinal cord cross-sectional area. Proportions of GM, WM, and cross-sectional area affected by T2 hyperintensity were calculated across 3 ROIs: 1) center axial section of lesion; 2) full lesion segment; and 3) full cord atlas volume. Spearman rank order correlation was calculated to compare MR metrics with clinical measures of disability. Proportion of GM metrics at the center axial section significantly correlated with measures of motor impairment upon admission ( r [9] = -0.78; P = .014) and at 3-month follow-up ( r [9] = -0.66; P = .05). Further, proportion of GM extracted across the full lesion segment significantly correlated with initial motor impairment ( r [9] = -0.74, P = .024). No significant correlation was found for proportion of WM or proportion of cross-sectional area with clinical disability. Atlas-based measures of proportion of GM T2 signal abnormality measured on a single axial MR imaging section and across the full lesion segment correlate with motor impairment and outcome in patients with acute flaccid myelitis. This is the first atlas-based study to correlate clinical outcomes with segmented measures of T2 signal abnormality in the spinal cord. © 2017 by American Journal of Neuroradiology.

  6. Spinal Interneurons and Forelimb Plasticity after Incomplete Cervical Spinal Cord Injury in Adult Rats

    PubMed Central

    Rombola, Angela M.; Rousseau, Celeste A.; Mercier, Lynne M.; Fitzpatrick, Garrett M.; Reier, Paul J.; Fuller, David D.; Lane, Michael A.

    2015-01-01

    Abstract Cervical spinal cord injury (cSCI) disrupts bulbospinal projections to motoneurons controlling the upper limbs, resulting in significant functional impairments. Ongoing clinical and experimental research has revealed several lines of evidence for functional neuroplasticity and recovery of upper extremity function after SCI. The underlying neural substrates, however, have not been thoroughly characterized. The goals of the present study were to map the intraspinal motor circuitry associated with a defined upper extremity muscle, and evaluate chronic changes in the distribution of this circuit following incomplete cSCI. Injured animals received a high cervical (C2) lateral hemisection (Hx), which compromises supraspinal input to ipsilateral spinal motoneurons controlling the upper extremities (forelimb) in the adult rat. A battery of behavioral tests was used to characterize the time course and extent of forelimb motor recovery over a 16 week period post-injury. A retrograde transneuronal tracer – pseudorabies virus – was used to define the motor and pre-motor circuitry controlling the extensor carpi radialis longus (ECRL) muscle in spinal intact and injured animals. In the spinal intact rat, labeling was observed unilaterally within the ECRL motoneuron pool and within spinal interneurons bilaterally distributed within the dorsal horn and intermediate gray matter. No changes in labeling were observed 16 weeks post-injury, despite a moderate degree of recovery of forelimb motor function. These results suggest that recovery of the forelimb function assessed following C2Hx injury does not involve recruitment of new interneurons into the ipsilateral ECRL motor pathway. However, the functional significance of these existing interneurons to motor recovery requires further exploration. PMID:25625912

  7. Hodgkin Lymphoma revealed by epidural spinal cord compression.

    PubMed

    Ghedira, Khalil; Matar, Nidhal; Bouali, Sofiene; Zehani, Alia; Boubaker, Adnen; Jemel, Hafedh

    2018-01-30

    Hodgkin Lymphoma is rarely diagnosed as spinal cord compression syndrome. Caused by an epidural mass, this complication is often encountered in a late stage of the disease. We report the case of a 40-year-old man presenting with symptoms of low thoracic spinal cord compression due to an epidural tumor on the MRI. Emergent surgery was undertaken on this patient, consisting in laminectomy and tumor resection. After surgery, pain relief and mild neurological improvement were noticed. The histological study revealed a Hodgkin Lymphoma and the patient was referred to chemotherapy and radiotherapy. Though chemotherapy is the gold standard treatment for Hodgkin Lymphoma, surgical spinal decompression may be required in epidural involvement of the disease. Diagnosis may be suspected in the presence of lymphadenopathy and general health decay.

  8. Measuring Fatigue in Persons with Spinal Cord Injury

    PubMed Central

    Anton, Hubert A.; Miller, William C.; Townson, Andrea F.

    2013-01-01

    Objective To evaluate the psychometric properties of the Fatigue Severity Scale (FSS) in persons with spinal cord injury (SCI). Design A two week methodological study was conducted to assess the internal consistency, reliability and the construct validity of the FSS. Setting A tertiary spinal cord rehabilitation facility. Participants 48 community living individuals at least one year post SCI with ASIA A or B SCI and no medical conditions causing fatigue. Main Outcome Measures The ASIA Impairment Scale; the FSS; a Visual Analogue Scale for Fatigue (VAS-F), the SF-36 vitality scale, and the Centre for Epidemiological Studies Depression – Scale (CES-D) Results Our sample was predominantly male (n=31, 65%) with tetraplegia (n=26, 54%) and ASIA A injuries (n=30, 63%). The mean FSS score at baseline was 4.4 (SD=1.4) with 54% (N=26) scoring greater than 4. The internal consistency of the FSS was Cronbach’s alpha = 0.89. Two-week test-retest reliability was ICC=0.84 (95% CI 0.74 – 0.90). The magnitude of the relationship was as hypothesized for the VAS-F(r=.67) and CES-D (r=.58) and lower than hypothesized for the vitality subscore (r=−.48) of the SF-36. Conclusions The FSS has acceptable reliability with regard to internal consistency, test-retest reliability, and validity in persons with motor complete SCI. PMID:18295634

  9. 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

  10. Cardiac dysfunctions following spinal cord injury

    PubMed Central

    Sandu, AM; Popescu, M; Iacobini, MA; Stoian, R; Neascu, C; Popa, F

    2009-01-01

    The aim of this article is to analyze cardiac dysfunctions occurring after spinal cord injury (SCI). Cardiac dysfunctions are common complications following SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. We reviewed epidemiology of cardiac disturbances after SCI, and neuroanatomy and pathophysiology of autonomic nervous system, sympathetic and parasympathetic. SCI causes disruption of descendent pathways from central control centers to spinal sympathetic neurons, originating into intermediolateral nuclei of T1–L2 spinal cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant cardiac dysfunction. Impairment of autonomic nervous control system, mostly in patients with cervical or high thoracic SCI, causes cardiac dysrrhythmias, especially bradycardia and, rarely, cardiac arrest, or tachyarrhytmias and hypotension. Specific complication dependent on the period of time after trauma like spinal shock and autonomic dysreflexia are also reviewed. Spinal shock occurs during the acute phase following SCI and is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe bradycardia and hypotension. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Besides all this, additional cardiac complications, such as cardiac deconditioning and coronary heart disease may also occur. Proper prophylaxis, including nonpharmacologic and pharmacological strategies and cardiac rehabilitation diminish occurrence of the cardiac dysfunction following

  11. Breaking bad news in spinal cord injury; a qualitative study assessing the perspective of spinal cord injury survivors in Turkey.

    PubMed

    Ozyemisci-Taskiran, Ozden; Coskun, Ozlem; Budakoglu, Isil Irem; Demirsoy, Nesrin

    2018-05-01

    Prior abstract publication: 2 nd Medical Rehabilitation Congress; Nov 4-7, 2010; Ankara, Turkey Objective: This study aims to investigate the process of breaking bad news from the perspective of spinal cord injury survivors. A cross sectional, qualitative study. Community. Fourteen spinal cord injury survivors. Subjects participated in a semi-structured interview about 'when', 'where' 'by whom' and 'how' they received and 'would' prefer to receive bad news. Answers to 'how' questions were coded according to SPIKES protocol (Setting, Perception, Invitation, Knowledge, Empathizing, Summary). Eight participants (57%) reported that they received bad news from a physician, mostly during rehabilitation. All would prefer to be informed by a physician and majority preferred to be gradually informed during rehabilitation. Half were not satisfied with the content of information. Only half felt that his/her physiatrist understood his/her emotional distress. Majority of participants who received bad news from physicians reported that the setting was private and their family members accompanied them. Most spinal cord injury survivors were unsatisfied with knowledge and emotional support provided by rehabilitation physicians. Participants would prefer to receive bad news by a senior physiatrist in a planned meeting during rehabilitation.

  12. Combined Effects of Acrobatic Exercise and Magnetic Stimulation on the Functional Recovery after Spinal Cord Lesions

    PubMed Central

    Wieraszko, Andrzej

    2008-01-01

    Abstract The objective of the study was to determine whether physical exercise combined with epidural spinal cord magnetic stimulation could improve recovery after injury of the spinal cord. Spinal cord lesioning in mice resulted in reduced locomotor function and negatively affected the muscle strength tested in vitro. Acrobatic exercise attenuated the behavioral effects of spinal cord injury. The exposure to magnetic fields facilitated further this improvement. The progress in behavioral recovery was correlated with reduced muscle degeneration and enhanced muscle contraction. The acrobatic exercise combined with stimulation with magnetic fields significantly facilitates behavioral recovery and muscle physiology in mice following spinal cord injury. PMID:18986227

  13. 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.

  14. 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.

  15. Alterations in the Genital Microbiota in Women With Spinal Cord Injury.

    PubMed

    Pires, Cristhiane V G; Linhares, Iara M; Serzedello, Felipe; Fukazawa, Eiko I; Baracat, Edmund C; Witkin, Steven S

    2016-02-01

    To evaluate the vaginal and cervical microbiota in women with spinal cord injury compared with mobile women. Fifty-two women with spinal cord injury (study group) and 57 mobile women (control group) were evaluated in a case-control study. All answered a structured questionnaire and were submitted to the following microbiological tests: microscopic examination of vaginal secretions for Trichomonas vaginalis and yeasts, Nugent score by Gram stain, bacterial culture, yeast culture, and endocervical sampling for Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma species. Candida species detected by direct microscopic examination of vaginal fluid was more common in women with spinal cord injuries than in control women: 17.3% (9/52) compared with 3.5% (2/57), respectively (P=.017). However, the frequency of yeast-positive cultures was similar in both groups (21.2% [10/52] compared with 15.8% [14/57]). Women with spinal cord injury were more likely to have positive vaginal cultures for Escherichia coli (15.4% [8/52] compared with 0% [0/57], P=.002) and Corynebacterium species (25.0% [13/52] compared with 8.8% [5/57], P=.037) and less likely for Lactobacillus species (63.5% [33/52] compared with 94.7% [54/57], P<.001). Women with spinal cord injury were more likely to have intermediate flora by Gram stain (Nugent score 4-6) than did the women in the control group (13.5% [7/52] compared with 1.8% [1/57], P=.033). The frequency of Mycoplasma species detection was similar in both groups (36.9% [18/52] compared with 34.6% [21/57]). No woman in either group was positive for T vaginalis, C trachomatis, or N gonorrhoeae. Women with spinal cord injury have an alteration in their vaginal microbiota away from a Lactobacillus species-dominated flora and a higher concentration of vaginal Candida species than do mobile women.

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

    PubMed

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

    2017-12-01

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

  17. 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.

  18. 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

  19. Longitudinal study of bone loss in chronic spinal cord injury patients

    PubMed Central

    Karapolat, Inanc; Karapolat, Hale Uzumcugil; Kirazli, Yesim; Capaci, Kazim; Akkoc, Yesim; Kumanlioglu, Kamil

    2015-01-01

    [Purpose] This prospective longitudinal study evaluated the changes in bone metabolism markers and bone mineral density of spinal cord injury patients over 3 years. We also assessed the relationships among the bone mineral density, bone metabolism, and clinical data of spinal cord injury patients. [Subjects and Methods] We assessed the clinical data (i.e., immobilization due to surgery, neurological status, neurological level, and extent of lesion) in 20 spinal cord injury patients. Bone mineral density, and hormonal and biochemical markers of the patients were measured at 0, 6, 12, and 36 months. [Results] Femoral neck T score decreased significantly at 36 months (p < 0.05). Among the hormonal markers, parathyroid hormone and vitamin D were significantly elevated, while bone turnover markers (i.e., deoxypyridinoline and osteocalcin) were significantly decreased at 12 and 36 months (p < 0.05). [Conclusion] Bone mineral density of the femoral neck decreases significantly during the long-term follow-up of patients with spinal cord injury due to osteoporosis. This could be due to changes in hormonal and bone turnover markers. PMID:26157234

  20. 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.

  1. Intrinsic Resting-State Functional Connectivity in the Human Spinal Cord at 3.0 T.

    PubMed

    San Emeterio Nateras, Oscar; Yu, Fang; Muir, Eric R; Bazan, Carlos; Franklin, Crystal G; Li, Wei; Li, Jinqi; Lancaster, Jack L; Duong, Timothy Q

    2016-04-01

    To apply resting-state functional magnetic resonance (MR) imaging to map functional connectivity of the human spinal cord. Studies were performed in nine self-declared healthy volunteers with informed consent and institutional review board approval. Resting-state functional MR imaging was performed to map functional connectivity of the human cervical spinal cord from C1 to C4 at 1 × 1 × 3-mm resolution with a 3.0-T clinical MR imaging unit. Independent component analysis (ICA) was performed to derive resting-state functional MR imaging z-score maps rendered on two-dimensional and three-dimensional images. Seed-based analysis was performed for cross validation with ICA networks by using Pearson correlation. Reproducibility analysis of resting-state functional MR imaging maps from four repeated trials in a single participant yielded a mean z score of 6 ± 1 (P < .0001). The centroid coordinates across the four trials deviated by 2 in-plane voxels ± 2 mm (standard deviation) and up to one adjacent image section ± 3 mm. ICA of group resting-state functional MR imaging data revealed prominent functional connectivity patterns within the spinal cord gray matter. There were statistically significant (z score > 3, P < .001) bilateral, unilateral, and intersegmental correlations in the ventral horns, dorsal horns, and central spinal cord gray matter. Three-dimensional surface rendering provided visualization of these components along the length of the spinal cord. Seed-based analysis showed that many ICA components exhibited strong and significant (P < .05) correlations, corroborating the ICA results. Resting-state functional MR imaging connectivity networks are qualitatively consistent with known neuroanatomic and functional structures in the spinal cord. Resting-state functional MR imaging of the human cervical spinal cord with a 3.0-T clinical MR imaging unit and standard MR imaging protocols and hardware reveals prominent functional connectivity patterns within the

  2. Spinal cord ischemia after simultaneous and sequential treatment of multilevel aortic disease.

    PubMed

    Piffaretti, Gabriele; Bonardelli, Stefano; Bellosta, Raffaello; Mariscalco, Giovanni; Lomazzi, Chiara; Tolenaar, Jip L; Zanotti, Camilla; Guadrini, Cristina; Sarcina, Antonio; Castelli, Patrizio; Trimarchi, Santi

    2014-10-01

    The aim of the present study is to report a risk analysis for spinal cord injury in a recent cohort of patients with simultaneous and sequential treatment of multilevel aortic disease. We performed a multicenter study with a retrospective data analysis. Simultaneous treatment refers to descending thoracic and infrarenal aortic lesions treated during the same operation, and sequential treatment refers to separate operations. All descending replacements were managed with endovascular repair. Of 4320 patients, multilevel aortic disease was detected in 77 (1.8%). Simultaneous repair was performed in 32 patients (41.5%), and a sequential repair was performed in 45 patients (58.4%). Postoperative spinal cord injury developed in 6 patients (7.8%). At multivariable analysis, the distance of the distal aortic neck from the celiac trunk was the only independent predictor of postoperative spinal cord injury (odds ratio, 0.75; 95% confidence interval, 0.56-0.99; P=.046); open surgical repair of the abdominal aortic disease was associated with a higher risk of spinal cord injury but did not reach statistical significance (odds ratio, 0.16; 95% confidence interval, 0.02-1.06; P=.057). Actuarial survival estimates at 1, 2, and 5 years after the procedure were 80%±5%, 68%±6%, and 63%±7%, respectively. Spinal cord injury did not impair survival (P=.885). In our experience, the risk of spinal cord injury is still substantial at 8% in patients with multilevel aortic disease. The distance of the distal landing zone from the celiac trunk is a significant predictor of spinal cord ischemia. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  3. Release and repair of a ventral thoracic spinal cord herniation.

    PubMed

    McCormick, Paul C

    2014-09-01

    Ventral thoracic spinal cord herniation is a rare but increasingly recognized cause of progressive myelopathy. This video demonstrates the imaging characteristics and surgical techniques for release and reduction of the spinal cord herniation as well as primary repair and reinforcement of the ventral dural hernia defect through an extended posterior approach. An instrumented fusion was concomitantly performed. The video can be found here: http://youtu.be/6Pcokep6Tug.

  4. The experience of seeking, gaining and maintaining employment after traumatic spinal cord injury and the vocational pathways involved.

    PubMed

    Hilton, Gillean; Unsworth, Carolyn A; Stuckey, Ruth; Murphy, Gregory C

    2018-01-01

    Vocational potential in people with spinal cord injury (SCI) are unrealised with rates of employment substantially lower than in the labour force participation of the general population and the pre-injury employment rates. To understand the experience and pathway of people achieving employment outcome after traumatic spinal cord injury by; classifying participants into employment outcome groups of stable, unstable and without employment; identifying pre and post-injury pathways for participants in each group and, exploring the experiences of people of seeking, gaining and maintaining employment. Thirty-one participants were interviewed. Mixed methods approach including interpretive phenomenological analysis and vocational pathway mapping of quantitative data. The most common pathway identified was from study and work pre-injury to stable employment post-injury. Four super-ordinate themes were identified from the interpretive phenomenological analysis; expectations of work, system impacts, worker identity and social supports. Implications for clinical practice include fostering cultural change, strategies for system navigation, promotion of worker identity and optimal use of social supports. The findings increase insight and understanding of the complex experience of employment after spinal cord injury. There is opportunity to guide experimental research, policy development and education concerning the complexity of the return to work experience and factors that influence pathways.

  5. Development of the International Spinal Cord Injury Activities and Participation Basic Data Set.

    PubMed

    Post, M W; Charlifue, S; Biering-Sørensen, F; Catz, A; Dijkers, M P; Horsewell, J; Noonan, V K; Noreau, L; Tate, D G; Sinnott, K A

    2016-07-01

    Consensus decision-making process. The objective of this study was to develop an International Spinal Cord Injury (SCI) Activities and Participation (A&P) Basic Data Set. International working group. A committee of experts was established to select and define A&P data elements to be included in this data set. A draft data set was developed and posted on the International Spinal Cord Society (ISCoS) and American Spinal Injury Association websites and was also disseminated among appropriate organizations for review. Suggested revisions were considered, and a final version of the A&P Data Set was completed. Consensus was reached to define A&P and to incorporate both performance and satisfaction ratings. Items that were considered core to each A&P domain were selected from two existing questionnaires. Four items measuring activities were selected from the Spinal Cord Independence Measure III to provide basic data on task execution in activities of daily living. Eight items were selected from the Craig Handicap Assessment and Reporting Technique to provide basic data on the frequency of participation. An additional rating of satisfaction on a three-point scale for each item completes the total of 24 A&P variables. Collection of the International SCI A&P Basic Data Set variables in all future research on SCI outcomes is advised to facilitate comparison of results across published studies from around the world. Additional standardised instruments to assess activities of daily living or participation can be administered, depending on the purpose of a particular study.

  6. 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.

  7. 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.

  8. Relationship of Personality and Locus of Control With Employment Outcomes among Participants with Spinal Cord Injury

    ERIC Educational Resources Information Center

    Krause, James S.; Broderick, Lynne

    2006-01-01

    We investigated relationships among personality, locus of control, and current post-injury employment status for 1,391 participants with spinal cord injury. Participants with higher internality locus-of-control scores and activity scores (personality) reported more favorable employment outcomes. Higher scores on chance and powerful others (locus…

  9. 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

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

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

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

    2016-01-22

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

  11. [Spinal cord injuries caused by aviation accidents].

    PubMed

    Heim, M; Ohry, A; Zeilig, G; Gur, S

    1992-05-15

    During the past 15 years fewer than 1% of those treated in the National Spinal Cord Injury Center were injured as a result of aviation accidents. In addition to 9 such patients treated at the center since 1973, another 6 were found among the many hundreds receiving ambulatory care in our clinics. 3 patients had survived a helicopter crash, 2 were injured while ejecting from combat aircraft, 3 were injured in crashes of light aircraft, 1 fell from a hand glider and 6 were injured in parachute drops. Of the 15 reviewed, 6 use wheelchairs, 3 walk assisted by orthopedic devices, while 6 ambulate freely. Although initial hospitalization was not substantially longer than in other patients with spinal cord injuries, extended ambulatory psychological intervention was necessary.

  12. 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

  13. Spinal cord stimulation for chronic pain.

    PubMed

    Mailis-Gagnon, A; Furlan, A D; Sandoval, J A; Taylor, R

    2004-01-01

    Spinal cord stimulation (SCS) is a form of therapy used to treat certain types of chronic pain. It involves an electrical generator that delivers pulses to a targeted spinal cord area. The leads can be implanted by laminectomy or percutaneously and the source of power is supplied by an implanted battery or by an external radio-frequency transmitter. The exact mechanism of action of SCS is poorly understood. To assess the efficacy and effectiveness of spinal cord stimulation in relieving certain kinds of pain, as well as the complications and adverse effects of this procedure. We searched MEDLINE and EMBASE to September 2003; the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2003); textbooks and reference lists in retrieved articles. We also contacted experts in the field of pain and the main manufacturer of the stimulators. We included trials with a control group, either randomized controlled trials (RCTs) or non-randomized controlled clinical trials (CCTs), that assessed spinal cord stimulation for chronic pain. Two independent reviewers selected the studies, assessed study quality and extracted the data. One of the assessors of methodological quality was blinded to authors, dates and journals. The data were analysed using qualitative methods (best evidence synthesis). Two RCTs (81 patients in total) met our inclusion criteria. One was judged as being of high quality (score of 3 on Jadad scale) and the other of low quality (score of 1 on Jadad scale). One trial included patients with Complex Regional Pain Syndrome Type I (reflex sympathetic dystrophy) and the other patients with Failed Back Surgery Syndrome. The follow-up periods varied from 6 to 12 months. Both studies reported that SCS was effective, however, meta-analysis was not undertaken because of the small number of patients and the heterogeneity of the study population. Although there is limited evidence in favour of SCS for Failed Back Surgery Syndrome and Complex Regional Pain

  14. Childhood Brain and Spinal Cord Tumors Treatment Overview (PDQ®)—Patient Version

    Cancer.gov

    Brain and spinal cord tumors may be benign (not cancer) or malignant (cancer). Both types cause signs or symptoms and need treatment. Get information about the many kinds of brain and spinal cord tumors, signs and symptoms, tests to diagnose, and treatment in this expert-reviewed summary.

  15. 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.

  16. 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.

  17. Phantom sensations in people with complete spinal cord lesions: a grounded theory perspective.

    PubMed

    Drysdale, Daren G; Shem, Kazuko; Walbom, Agnes; Miner, Maureen D; Maclachlan, Malcolm

    2009-01-01

    Phantom sensations are somatic phenomena arising from denervated parts of the body. There is very little research, and much diagnostic confusion, regarding such experiences in people with spinal cord injuries. In the case of 'complete' spinal cord lesions, phantom experiences may challenge, and indeed, contradict, the understanding that both clinicians and patients have of such injuries. This paper seeks to provide a better understanding of such 'phantom' sensations in spinal cord injury. We used grounded theory methods to explore 'phantom' sensations as experienced by individuals with complete (ASIA A) spinal lesions. Eight people with complete lesions, who were selected through theoretical sampling, participated in a semi-structured interview. Emergent themes included injury context, sensations experienced, the meaning of sensations, body connectivity, attitude and communication about sensations. Our results provide an enhanced understanding of the embodied experience of phantom sensations, and important insights regarding self-construction and rehabilitative processes in people with spinal cord injury who experience such anomalous sensations.

  18. 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.

  19. Subarachnoid-to-Subarachnoid Shunt for Correction of Nonfunctioning Baclofen Pump in a Severe Case of Chronic Debilitating Post-Spinal Cord Injury Spasticity.

    PubMed

    Bakare, Adewale A; Weyhenmeyer, Jonathan; Lee, Albert

    2018-02-01

    Perhaps the most disabling condition seen in patients with spinal cord injury (SCI) is spasticity. Spasticity is characterized as hyperreflexia and hypertonicity as a result of damage to the supraspinal tracts in the aftermath of SCI. Intrathecal baclofen (ITB) is the mainstay therapy for spasticity unresponsive to oral baclofen. One of the problems associated with post-SCI spasticity unresponsive to ITB is the development of scar tissue that prevents the diffusion of baclofen in the desired spinal cord area. This case offers a unique strategy to deal with multilevel scar tissue. This 46-year-old paraplegic male with a T8 SCI whose spasticity had been well managed with ITB therapy for many years recently suffered intractable spasticity necessitating multiple reoperations for a nonfunctioning ITB catheter secondary to extensive scar tissue and intrathecal adhesions. Placement of a subarachnoid-to-subarachnoid shunt eliminated the problem of extensive scar tissue preventing adequate baclofen therapy. After undergoing multilevel thoracic and lumbar laminectomies with subarachnoid-to-subarachnoid spinal shunt, the patient's spasticity was finally brought under control with adequate daily baclofen infusion. This case demonstrates a creative way to address ITB catheter failure before considering other measures, such as neuroablative procedures (e.g., rhizotomy, myelotomy). This case reinforces the recommendation that ablative procedures, which have far greater complications, should be reserved for patients who have failed medical or other nonablative therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. The kinematic recovery process of rhesus monkeys after spinal cord injury.

    PubMed

    Wei, Rui-Han; Zhao, Can; Rao, Jia-Sheng; Zhao, Wen; Zhou, Xia; Tian, Peng-Yu; Song, Wei; Ji, Run; Zhang, Ai-Feng; Yang, Zhao-Yang; Li, Xiao-Guang

    2018-05-16

    After incomplete spinal cord injury (SCI), neural circuits may be plastically reconstructed to some degree, resulting in extensive functional locomotor recovery. The present study aimed to observe the post-SCI locomotor recovery of rhesus monkey hindlimbs and compare the recovery degrees of different hindlimb parts, thus revealing the recovery process of locomotor function. Four rhesus monkeys were chosen for thoracic hemisection injury. The hindlimb locomotor performance of these animals was recorded before surgery, as well as 6 and 12 weeks post-lesion. Via principal component analysis, the relevant parameters of the limb endpoint, pelvis, hindlimb segments, and joints were processed and analyzed. Twelve weeks after surgery, partial kinematic recovery was observed at the limb endpoint, shank, foot, and knee joints, and the locomotor performance of the ankle joint even recovered to the pre-lesion level; the elevation angle of the thigh and hip joints showed no obvious recovery. Generally, different parts of a monkey hindlimb had different spontaneous recovery processes; specifically, the closer the part was to the distal end, the more extensive was the locomotor function recovery. Therefore, we speculate that locomotor recovery may be attributed to plastic reconstruction of the motor circuits that are mainly composed of corticospinal tract. This would help to further understand the plasticity of motor circuits after spinal cord injury.

  1. MRI and MRA of spinal cord arteriovenous shunts.

    PubMed

    Condette-Auliac, Stéphanie; Boulin, Anne; Roccatagliata, Luca; Coskun, Oguzhan; Guieu, Stéphanie; Guedin, Pierre; Rodesch, Georges

    2014-12-01

    The purpose of this review is to describe the diagnostic criteria for spinal cord arteriovenous shunts (SCAVSs) when using magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), and to discuss the extent to which the different MRI and MRA sequences and technical parameters provide the information that is required to diagnose these lesions properly. SCAVSs are divided into four groups according to location (paraspinal, epidural, dural, or intradural) and type (fistula or nidus); each type of lesion is described. SCAVSs are responsible for neurological symptoms due to spinal cord or nerve root involvement. MRI is usually the first examination performed when a spinal cord lesion is suspected. Recognition of the image characteristics of vascular lesions is mandatory if useful sequences are to be performed-especially MRA sequences. Because the treatment of SCAVSs relies mainly on endovascular therapies, MRI and MRA help with the planning of the angiographic procedure. We explain the choice of MRA sequences and parameters, the advantages and pitfalls to be aware of in order to obtain the best visualization, and the analysis of each lesion. © 2014 Wiley Periodicals, Inc.

  2. 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

  3. Rapid myelin water imaging in human cervical spinal cord.

    PubMed

    Ljungberg, Emil; Vavasour, Irene; Tam, Roger; Yoo, Youngjin; Rauscher, Alexander; Li, David K B; Traboulsee, Anthony; MacKay, Alex; Kolind, Shannon

    2017-10-01

    Myelin water imaging (MWI) using multi-echo T 2 relaxation is a quantitative MRI technique that can be used as an in vivo biomarker for myelin in the central nervous system. MWI using a multi-echo spin echo sequence currently takes more than 20 min to acquire eight axial slices (5 mm thickness) in the cervical spinal cord, making spinal cord MWI impractical for implementation in clinical studies. In this study, an accelerated gradient and spin echo sequence (GRASE), previously validated for brain MWI, was adapted for spinal cord MWI. Ten healthy volunteers were scanned with the GRASE sequence (acquisition time 8.5 min) and compared with the multi-echo spin echo sequence (acquisition time 23.5 min). Using region of interest analysis, myelin estimates obtained from the two sequences were found to be in good agreement (mean difference = -0.0092, 95% confidence interval =  - 0.0092 ± 0.061; regression slope = 1.01, ρ = 0.9). MWI using GRASE was shown to be highly reproducible with an average coefficient of variation of 6.1%. The results from this study show that MWI can be performed in the cervical spinal cord in less than 10 min, allowing for practical implementation in multimodal clinical studies. Magn Reson Med 78:1482-1487, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  4. The "pseudo-CT myelogram sign": an aid to the diagnosis of underlying brain stem and spinal cord trauma in the presence of major craniocervical region injury on post-mortem CT.

    PubMed

    Bolster, F; Ali, Z; Daly, B

    2017-12-01

    To document the detection of underlying low-attenuation spinal cord or brain stem injuries in the presence of the "pseudo-CT myelogram sign" (PCMS) on post-mortem computed tomography (PMCT). The PCMS was identified on PMCT in 20 decedents (11 male, nine female; age 3-83 years, mean age 35.3 years) following fatal blunt trauma at a single forensic centre. Osseous and ligamentous craniocervical region injuries and brain stem or spinal cord trauma detectable on PMCT were recorded. PMCT findings were compared to conventional autopsy in all cases. PMCT-detected transection of the brain stem or high cervical cord in nine of 10 cases compared to autopsy (90% sensitivity). PMCT was 92.86% sensitive in detection of atlanto-occipital joint injuries (n=14), and 100% sensitive for atlanto-axial joint (n=8) injuries. PMCT detected more cervical spine and skull base fractures (n=22, and n=10, respectively) compared to autopsy (n=13, and n=5, respectively). The PCMS is a novel description of a diagnostic finding, which if present in fatal craniocervical region trauma, is very sensitive for underlying spinal cord and brain stem injuries not ordinarily visible on PMCT. Its presence may also predict major osseous and/or ligamentous injuries in this region when anatomical displacement is not evident on PMCT. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  5. Delayed inflammatory mRNA and protein expression after spinal cord injury

    PubMed Central

    2011-01-01

    Background Spinal cord injury (SCI) induces secondary tissue damage that is associated with inflammation. We have previously demonstrated that inflammation-related gene expression after SCI occurs in two waves - an initial cluster that is acutely and transiently up-regulated within 24 hours, and a more delayed cluster that peaks between 72 hours and 7 days. Here we extend the microarray analysis of these gene clusters up to 6 months post-SCI. Methods Adult male rats were subjected to mild, moderate or severe spinal cord contusion injury at T9 using a well-characterized weight-drop model. Tissue from the lesion epicenter was obtained 4 hours, 24 hours, 7 days, 28 days, 3 months or 6 months post-injury and processed for microarray analysis and protein expression. Results Anchor gene analysis using C1qB revealed a cluster of genes that showed elevated expression through 6 months post-injury, including galectin-3, p22PHOX, gp91PHOX, CD53 and progranulin. The expression of these genes occurred primarily in microglia/macrophage cells and was confirmed at the protein level using both immunohistochemistry and western blotting. As p22PHOX and gp91PHOX are components of the NADPH oxidase enzyme, enzymatic activity and its role in SCI were assessed and NADPH oxidase activity was found to be significantly up-regulated through 6 months post-injury. Further, treating rats with the nonspecific, irreversible NADPH oxidase inhibitor diphenylene iodinium (DPI) reduced both lesion volume and expression of chronic gene cluster proteins one month after trauma. Conclusions These data demonstrate that inflammation-related genes are chronically up-regulated after SCI and may contribute to further tissue loss. PMID:21975064

  6. Sexuality and sexual life in women with spinal cord injury: a controlled study.

    PubMed

    Kreuter, Margareta; Siösteen, Agneta; Biering-Sørensen, Fin

    2008-01-01

    To describe sexual life in women with spinal cord injury. Controlled cross-sectional, questionnaire. Women, 18-65 years, treated at spinal cord centres in Sweden, Denmark, Norway, Finland and Iceland. 545 women (57%) completed the questionnaires. The age-matched control group consisted of 507 women. The 104-item Spinal Cord Injury Women Questionnaire, was designed to assess different dimensions of sexuality. 80% of the women with spinal cord injury had engaged in sex after the injury. Reasons for not wanting or not having the courage to be intimate and sexual were physical problems, low sexual desire, low self-esteem and feelings of being unattractive. The motivations of both the women with spinal cord injury and controls to engage in sexual activity were intimacy-based rather than primarily sexual. Being in the right mood both before and during sex to become receptive to sexual stimulation was important. For women who are able to overcome the physical restrictions and mental obstacles due to injury, it is possible to regain an active and positive sexual life together with a partner. Sexual information and counselling should be available both during initial rehabilitation and later when the women have returned to their homes.

  7. Spinal cord lesions of progressive multifocal leukoencephalopathy in an acquired immunodeficiency syndrome patient.

    PubMed

    Bernal-Cano, F; Joseph, J T; Koralnik, I J

    2007-10-01

    Progressive multifocal leukoencephalopathy (PML) is a deadly demyelinating disease of the central nervous system, which occurs in immunosuppressed individuals. This disease is caused by a reactivation of the polyomavirus JC (JCV). Clinical presentation can be variable from patient to patient as lesions can occur anywhere in the CNS white matter; however, they appear to spare the optic nerves and the spinal cord. The authors present a case of PML in the setting of acquired immunodeficiency syndrome (AIDS) who developed PML lesions in the spinal cord, discovered during the postmortem examination. This finding is significant because PML has recently been diagnosed in patients with multiple sclerosis (MS) treated with the novel immunomodulatory medication natalizumab. Indeed, spinal cord lesions are frequent in MS. Therefore clinicians should be aware that in addition to the brain, PML may also affect the spinal cord white matter.

  8. Long-lasting involuntary motor activity after spinal cord injury.

    PubMed

    McKay, W B; Ovechkin, A V; Vitaz, T W; Terson de Paleville, D G L; Harkema, S J

    2011-01-01

    The study design used is prospective cohort study. This study was designed to neurophysiologically characterize spinal motor activity during recovery from spinal cord injury (SCI). University of Louisville, Louisville, Kentucky, USA. Twenty-five consecutive acute SCI admissions were recruited for this study. The American Spinal Injury Association Impairment Scale (AIS) was used to categorize injury level and severity at onset. Surface EMG recording was carried out initially between the day of admission and 17 days post-onset (6.0 ± 4.3, mean ± s.d. days). Follow-up recordings were performed for up to 9 months after injury. Initial AIS distribution was 7 AIS-A; 3 AIS-B; 2 AIS-C; 13 AIS-D. Twelve subjects (48%) showed long-duration involuntary motor-unit activation during relaxation. This activity was seen on initial examination in nine and on follow-up by 3 months post-injury in three others. It was seen in muscles innervated from the injury zone in 11 and caudal to the lesion in 9 subjects. This activity was independent of the presence or absence of tendon reflexes and the ability to volitionally suppress plantar stimulation elicited reflex withdrawal. The form of involuntary activity described here is the likely result of the altered balance of excitation and inhibition reaching spinal motor neurons because of the loss of inhibitory interneurons or their reduced activation by damaged supraspinal drive and the synaptic reorganization that follows SCI. As such, this activity may be useful for monitoring the effects of neuroprotective and restorative intervention strategies in persons with SCI.

  9. Long-lasting Involuntary Motor Activity After Spinal Cord Injury

    PubMed Central

    McKay, WB; Ovechkin, AV; Vitaz, TW; de Paleville, DGLTerson; Harkema, SJ

    2010-01-01

    Study Design Prospective cohort study Objective This study was designed to neurophysiologically characterize spinal motor activity during recovery from spinal cord injury (SCI). Setting University of Louisville, Louisville, Kentucky, USA. Material Twenty five consecutive acute SCI admissions were recruited for this study. Methods The American Spinal Injury Association Impairment Scale (AIS) was used to categorize injury level and severity at onset. Surface EMG recording, was carried out initially between the day of admission and 17 days post onset (6.0 ± 4.3, mean ± SD days). Follow-up recordings were performed for up to 9 months after injury. Initial AIS distribution was: 7 AIS-A; 3 AIS-B; 2 AIS-C; 13 AIS-D. Results Twelve subjects (48%) showed long-duration involuntary motor unit activation during relaxation. This activity was seen on initial examination in nine and on follow-up by three months post-injury in three others. It was seen in muscles innervated from the injury zone in 11 and caudal to the lesion in 9 subjects. This activity was independent of the presence or absence of tendon reflexes and the ability to volitionally suppress plantar stimulation elicited reflex withdrawal. Conclusions The form of involuntary activity described here is the likely result of the altered balance of excitation and inhibition reaching spinal motor neurons due to the loss of inhibitory interneurons or their reduced activation by damaged supraspinal drive and the synaptic reorganization that follows SCI. As such, this activity may be useful for monitoring the effects of neuroprotective and restorative intervention strategies in persons with SCI. PMID:20585326

  10. Rehabilitation outcomes following traumatic spinal cord injury in a tertiary spinal cord injury centre: a comparison with an international standard.

    PubMed

    Chan, S C C; Chan, A P S

    2005-08-01

    Retrospective descriptive analysis of data of patients with traumatic spinal cord injury (SCI) in a tertiary SCI centre. To identify the characteristics of the rehabilitation outcomes of patients with different levels of traumatic SCI and to compare the results with data reported in the American Consortium for Spinal Cord Medicine. A newly established tertiary SCI centre in Tai Po Hospital, Tai Po, Hong Kong. A total of 33 patients with traumatic SCI admitted in 2002 were included in the study. They were classified into different ASIA subgroups based on their levels and completeness of injury. The functional status changes measured by the Functional Independence Measure (FIM) (on admission, placement and upon discharge, and at 1 and 3 months post discharge) and discharge placement were recorded as rehabilitation outcomes. A total, 24 patients were tetraplegic while nine were paraplegic. Seven and two from tetraplegic and paraplegic groups were readmitted with late complications due to urinary tract infection, spasticity and/or occurrence of pressure sores. The mean age was found to be 48.36 (SD=15.64) years. In all, 16 (48.48%) sustained the injury from falling from height. The trend of FIM motor scores at discharge across different ASIA subgroups appeared to be comparable to those reported in the American Consortium for Spinal Cord Medicine with scores generally lower. Significant functional improvements during the hospital phase were found in the two tetraplegic and paraplegic ASIA D subgroups (t3=3.430, P<0.05; t2=4.083, P=0.55, respectively). Significant differences were also revealed among subgroups (F(7,32)=6.625, P<0.0005) with lower level tetraplegic groups appearing to stay much longer in the rehabilitation centre. In all, 64.5% of newly diagnosed patients returned to live in the community. This report gives a preliminary overview on the characteristics of rehabilitation outcomes in one of the SCI centres in Hong Kong in relation to the international

  11. Spinal Cord Infarction in Clinical Neurology: A Review of Characteristics and Long-Term Prognosis in Comparison to Cerebral Infarction.

    PubMed

    Romi, Fredrik; Naess, Halvor

    2016-01-01

    Spinal cord stroke is rare accounting for 0.3-1% of all strokes and is classified into upper (cervical) and lower (thoracolumbar) strokes. Patients present with severe deficits but later often show good functional improvement. On admission, younger age, male gender, hypertension, diabetes mellitus and elevated blood glucose indicate more severe spinal cord strokes. Treatment of these risk factors is essential in the acute phase. Biphasic spinal cord strokes are seen in one-fifth of the patients. These present with acute or transient sensory spinal cord deficits often preceded by radiating pain between the shoulders, and should be considered and treated as imminent spinal cord strokes. Spinal cord infarction patients are younger and more often women compared to cerebral infarction patients. Traditional cerebrovascular risk factors are less relevant in spinal cord infarction. Spinal cord infarction patients are more likely to be discharged home and show better improvement after initial treatment compared to cerebral infarction patients. On long-term follow-up, spinal cord infarction patients have lower mortality and higher emotional well-being scores than cerebral infarction patients. Despite more chronic pain, the frequency of re-employment is higher among spinal cord infarction patients compared to cerebral infarction patients who are more often afflicted with cognitive function deficits. © 2016 S. Karger AG, Basel.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. [Posttraumatic syringomyelia in 2 patients with thoracic spinal cord lesions].

    PubMed

    Bollen, A E; Hoving, E W; Kuks, J B

    2000-04-29

    Two patients, men aged 42 and 40 years, developed new neurological symptoms 3 months and 22 years, respectively, after a traumatic high thoracic spinal cord injury. The MRI scan showed a cavity in the central part of the spinal cord, on which the diagnosis of 'posttraumatic syringomyelia' could be based. In one of the patients a syringo-subarachnoidal shunt was created, the other was treated conservatively because of a severe concomitant thoracic kyphosis. Posttraumatic syringomyelia is a potentially life-threathening late complication of spinal cord injury and is characterized by development of new neurological symptoms after a variable time interval. The most typical symptom of non-traumatic syringomyelia, viz. diminution of vital sensitivity without loss of gnostic sensitivity, is not necessarily present in posttraumatic syringomyelia. Surgical treatment of posttraumatic syringomyelia is advocated if there is progressive neurological deterioration, and consists of drainage of the syrinx.

  17. Lifestyle and health conditions of adults with spinal cord injury.

    PubMed

    Xavier de França, Inacia Sátiro; Cruz Enders, Bertha; Silva Coura, Alexsandro; Pereira Cruz, Giovanna Karinny; da Silva Aragão, Jamilly; Carvalho de Oliveira, Déborah Raquel

    2014-01-01

    . To describe the lifestyle of adults with spinal cord injury and explore its relation with some health conditions. Cross sectional study, in which a questionnaire containing sociodemographic, habits and health conditions variables was used. Forty-seven people with spinal cord injury participated and answered the self-report questionnaire. The group under study was predominantly male (92%), under 40 years of age (47%), and had low educational level (76%). The most frequent risk factors related to the lifestyle were: smoking (28%), alcohol consumption (36%), coffee consumption (92%) and being physically inactive (64%). Association was found between having four or more risk factors related to lifestyle and the loss of appetite, as well as constipation. . The actual inadequate lifestyle is associated with the health conditions of patients, and the nursing team should pay special attention to the education and promotion of health related to people with spinal cord injury.

  18. 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

  19. Body composition of active persons with spinal cord injury and with poliomyelitis

    USDA-ARS?s Scientific Manuscript database

    This study sought to evaluate the body composition of subjects with active spinal cord injuries and polio. Two groups of males and females, active, free-living, of similar ages and body mass index (BMI), were distributed according to the source of deficiency: SCI – low spinal cord injury (T5-T12) an...

  20. 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

  1. Worklife After Traumatic Spinal Cord Injury

    PubMed Central

    Pflaum, Christopher; McCollister, George; Strauss, David J; Shavelle, Robert M; DeVivo, Michael J

    2006-01-01

    Objective: To develop predictive models to estimate worklife expectancy after spinal cord injury (SCI). Design: Inception cohort study. Setting: Model SCI Care Systems throughout the United States. Participants: 20,143 persons enrolled in the National Spinal Cord Injury Statistical Center database since 1973. Intervention: Not applicable. Main Outcome Measure: Postinjury employment rates and worklife expectancy. Results: Using logistic regression, we found a greater likelihood of being employed in any given year to be significantly associated with younger age, white race, higher education level, being married, having a nonviolent cause of injury, paraplegia, ASIA D injury, longer time postinjury, being employed at injury and during the previous postinjury year, higher general population employment rate, lower level of Social Security Disability Insurance benefits, and calendar years after the passage of the Americans with Disabilities Act. Conclusions: The likelihood of postinjury employment varies substantially among persons with SCI. Given favorable patient characteristics, worklife should be considerably higher than previous estimates. PMID:17044388

  2. Therapeutic Effect of Platelet-Rich Plasma in Rat Spinal Cord Injuries

    PubMed Central

    Chen, Nan-Fu; Sung, Chun-Sung; Wen, Zhi-Hong; Chen, Chun-Hong; Feng, Chien-Wei; Hung, Han-Chun; Yang, San-Nan; Tsui, Kuan-Hao; Chen, Wu-Fu

    2018-01-01

    Platelet-rich plasma (PRP) is prepared by centrifuging fresh blood in an anticoagulant state, and harvesting the platelet-rich portion or condensing platelets. Studies have consistently demonstrated that PRP concentrates are an abundant source of growth factors, such as platelet-derived growth factor (PDGF), transforming growth factor β (TGF-β), insulin-like growth factor 1 (IGF-1), and epithelial growth factor (EGF). The complex mechanisms underlying spinal cord injury (SCI) diminish intrinsic repair and neuronal regeneration. Several studies have suggested that growth factor-promoted axonal regeneration can occur for an extended period after injury. More importantly, the delivery of exogenous growth factors contained in PRP, such as EGF, IGF-1, and TGF-β, has neurotrophic effects on central nervous system (CNS) injuries and neurodegenerative diseases. However, only a few studies have investigated the effects of PRP on CNS injuries or neurodegenerative diseases. According to our review of relevant literature, no study has investigated the effect of intrathecal (i.t.) PRP injection into the injured spinal cord and activation of intrinsic mechanisms. In the present study, we directly injected i.t. PRP into rat spinal cords and examined the effects of PRP on normal and injured spinal cords. In rats with normal spinal cords, PRP induced microglia and astrocyte activation and PDGF-B and ICAM-1 expression. In rats with SCIs, i.t. PRP enhanced the locomotor recovery and spared white matter, promoted angiogenesis and neuronal regeneration, and modulated blood vessel size. Furthermore, a sustained treatment (a bolus of PRP followed by a 1/3 dose of initial PRP concentration) exerted more favorable therapeutic effects than a single dose of PRP. Our findings suggest by i.t. PRP stimulate angiogenesis, enhancing neuronal regeneration after SCI in rats. Although PRP induces minor inflammation in normal and injured spinal cords, it has many advantages. It is an autologous

  3. Resilience and the rehabilitation of adult spinal cord injury survivors: A qualitative systematic review.

    PubMed

    Kornhaber, Rachel; Mclean, Loyola; Betihavas, Vasiliki; Cleary, Michelle

    2018-01-01

    To synthesize the qualitative research evidence that explored how survivors of adult spinal cord injury experience and make sense of resilience. Spinal cord injury is often a sudden and unexpected life-changing event requiring complex and long-term rehabilitation. The development of resilience is essential in determining how spinal cord injury survivors negotiate this injury and rehabilitation. A qualitative systematic review and thematic synthesis of the research evidence. CINAHL, PubMed, Embase, Scopus and PsycINFO were searched, no restriction dates were used. Methodological quality was assessed using the Critical Appraisal Skills Programme checklist. Thematic synthesis focused on how survivors of adult spinal cord injury experience and make sense of resilience. Six qualitative research articles reported the experiences of 84 spinal cord injury survivors. Themes identified were: uncertainty and regaining independence; prior experiences of resilience; adopting resilient thinking; and strengthening resilience through supports. Recovery and rehabilitation following spinal cord survivors is influenced by the individual's capacity for resilience. Resilience may be influenced by previous life experiences and enhanced by supportive nursing staff encouraging self-efficacy. Survivors identified the need for active involvement in decision-making about their care to enable a sense of regaining control of their lives. This has the potential to have a significant impact on their self-efficacy and in turn health outcomes. © 2017 John Wiley & Sons Ltd.

  4. 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.

  5. 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.

  6. 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

  7. Back pain: a real target for spinal cord stimulation?

    PubMed

    Rigoard, Philippe; Delmotte, Alexandre; D'Houtaud, Samuel; Misbert, Lorraine; Diallo, Bakari; Roy-Moreau, Aline; Durand, Sylvain; Royoux, Solène; Giot, Jean-Philippe; Bataille, Benoit

    2012-03-01

    Failed back surgery syndrome represents one of the most frequent etiologies of chronic back pain and is a major public health issue. Neurostimulation has currently not been validated in the treatment of back pain because of technological limitations in implantable spinal cord stimulation (SCS) systems. New-generation leads using several columns of stimulation can generate longitudinal and/or transverse stimulation fields into the spinal cord. To investigate, through extensive stimulation testing, the capacity of multicolumn tripolar leads to achieve back territory paresthesia coverage in refractory failed back surgery syndrome patients. Eleven patients implanted with a 16-contact spinal cord stimulation lead (Specify 5-6-5, Medtronic Inc) were assessed with a systematic exploration of 43 selected stimulation configurations to generate bilateral back paresthesia in addition to leg territory coverage. The tripolar lead successfully generated paresthesia in both bilateral back and leg territories in 9 patients (81.8%). Success rates of multicolumn stimulation patterns were significantly higher than for longitudinal configurations for lombodorsal paresthesia coverage. Six months after implantation, significant pain relief was obtained compared with preoperative evaluation for global pain (Visual Analog Scale, 2.25 vs 8.2 preoperatively; P < .05), leg pain (Visual Analog Scale, 0.5 vs 7.6 preoperatively; P < .05), and back pain (Visual Analog Scale, 1.5 vs 7.8 preoperatively; P < .05). These results suggest that multicolumn leads can reliably generate back pain coverage and favor pain relief outcomes. This may lead physicians to reconsider new indications for spinal cord stimulation. Expanding neurostimulation perspectives to intractable back pain syndromes could become realistic in the near future.

  8. 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

  9. 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.

  10. Heterogeneity of Opioid Binding Sites in Guinea Pig Spinal Cord

    DTIC Science & Technology

    1984-11-30

    the release of substance P from spinal cord. Substance P is one of the putative transmitters of y nociceptive i m p u l ^ (Lembeck et al., 1981), and...is located in primary afferents of spinal cord (Jessel et al., 1978). Demonstration of morphine’s abil it/ to inhibit the relea^ of substance P ...demonstrate enkephalin’s ability to inhibit substance P relea^ from senajry neurons in culture as well as to cteirease the action potential of these

  11. 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.

  12. Subarachnoid Hemorrhage due to Spinal Cord Schwannoma Presenting Findings Mimicking Meningitis.

    PubMed

    Zhang, Hong-Mei; Zhang, Yin-Xi; Zhang, Qing; Song, Shui-Jiang; Liu, Zhi-Rong

    2016-08-01

    Subarachnoid hemorrhage (SAH) of spinal origin is uncommon in clinical practice, and spinal schwannomas associated with SAH are even more rarely reported. We report an unusual case of spinal SAH mimicking meningitis with normal brain computed tomography (CT)/magnetic resonance imaging (MRI) and negative CT angiography. Cerebrospinal fluid examination results were consistent with the manifestation of SAH. Spinal MRI performed subsequently showed an intradural extramedullary mass. The patient received surgery and was finally diagnosed with spinal cord schwannoma. A retrospective chart review of the patient was performed. We describe a case of SAH due to spinal cord schwannoma. Our case highlights the importance of careful history taking and complete evaluation. We emphasize that spinal causes should always be ruled out in patients with angionegative SAH and that schwannoma should be considered in the differential diagnosis of SAH etiologies even though rare. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

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

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-2-0132 TITLE: Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal Cord Injury...Sept 2015 4. TITLE AND SUBTITLE Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal Cord Injury 5a...evaluate the restoration of bladder and bowel function using electrical stimulation and block after spinal cord injury in human subjects. All staff

  14. 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.

  15. Preexisting severe cervical spinal cord compression is a significant risk factor for severe paralysis development in patients with traumatic cervical spinal cord injury without bone injury: a retrospective cohort study.

    PubMed

    Oichi, Takeshi; Oshima, Yasushi; Okazaki, Rentaro; Azuma, Seiichi

    2016-01-01

    The objective of this study is to investigate whether preexisting severe cervical spinal cord compression affects the severity of paralysis once patients develop traumatic cervical spinal cord injury (CSCI) without bone injury. We retrospectively investigated 122 consecutive patients with traumatic CSCI without bone injury. The severity of paralysis on admission was assessed by the American Spinal Injury Association impairment scale (AIS). The degree of preexisting cervical spinal cord compression was evaluated by the maximum spinal cord compression (MSCC) and was divided into three categories: minor compression (MSCC ≤ 20 %), moderate compression (20 % < MSCC ≤ 40 %), and severe compression (40 % < MSCC). We investigated soft-tissue damage on magnetic resonance imaging to estimate the external force applied. Other potential risk factors, including age, sex, fused vertebra, and ossification of longitudinal ligament, were also reviewed. A multivariate logistic regression analysis was performed to investigate the risk factors for developing severe paralysis (AIS A-C) on admission. Our study included 103 males and 19 females with mean age of 65 years. Sixty-one patients showed severe paralysis (AIS A-C) on admission. The average MSCC was 22 %. Moderate compression was observed in 41, and severe in 20. Soft-tissue damage was observed in 91. A multivariate analysis showed that severe cervical spinal cord compression significantly affected the severity of paralysis at the time of injury, whereas both mild and moderate compression did not affect it. Soft-tissue damage was also significantly associated with severe paralysis on admission. Preexisting severe cervical cord compression is an independent risk factor for severe paralysis once patients develop traumatic CSCI without bone injury.

  16. The Prevalence and Phenotype of Activated Microglia/Macrophages within the Spinal Cord of the Hyperostotic Mouse (twy/twy) Changes in Response to Chronic Progressive Spinal Cord Compression: Implications for Human Cervical Compressive Myelopathy

    PubMed Central

    Hirai, Takayuki; Uchida, Kenzo; Nakajima, Hideaki; Guerrero, Alexander Rodriguez; Takeura, Naoto; Watanabe, Shuji; Sugita, Daisuke; Yoshida, Ai; Johnson, William E. B.; Baba, Hisatoshi

    2013-01-01

    Background Cervical compressive myelopathy, e.g. due to spondylosis or ossification of the posterior longitudinal ligament is a common cause of spinal cord dysfunction. Although human pathological studies have reported neuronal loss and demyelination in the chronically compressed spinal cord, little is known about the mechanisms involved. In particular, the neuroinflammatory processes that are thought to underlie the condition are poorly understood. The present study assessed the localized prevalence of activated M1 and M2 microglia/macrophages in twy/twy mice that develop spontaneous cervical spinal cord compression, as a model of human disease. Methods Inflammatory cells and cytokines were assessed in compressed lesions of the spinal cords in 12-, 18- and 24-weeks old twy/twy mice by immunohistochemical, immunoblot and flow cytometric analysis. Computed tomography and standard histology confirmed a progressive spinal cord compression through the spontaneously development of an impinging calcified mass. Results The prevalence of CD11b-positive cells, in the compressed spinal cord increased over time with a concurrent decrease in neurons. The CD11b-positive cell population was initially formed of arginase-1- and CD206-positive M2 microglia/macrophages, which later shifted towards iNOS- and CD16/32-positive M1 microglia/macrophages. There was a transient increase in levels of T helper 2 (Th2) cytokines at 18 weeks, whereas levels of Th1 cytokines as well as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and macrophage antigen (Mac) −2 progressively increased. Conclusions Spinal cord compression was associated with a temporal M2 microglia/macrophage response, which may act as a possible repair or neuroprotective mechanism. However, the persistence of the neural insult also associated with persistent expression of Th1 cytokines and increased prevalence of activated M1 microglia/macrophages, which may lead to neuronal loss and demyelination

  17. Chondroitin sulfates do not impede axonal regeneration in goldfish spinal cord.

    PubMed

    Takeda, Akihito; Okada, Soichiro; Funakoshi, Kengo

    2017-10-15

    Chondroitin sulfate proteoglycans produced in glial scar tissue are a major inhibitory factor for axonal regeneration after central nervous system injury in mammals. The inhibition is largely due to chondroitin sulfates, whose effects differ according to the sulfation pattern. In contrast to mammals, fish nerves spontaneously regenerate beyond the scar tissue after spinal cord injury, although the mechanisms that allow for axons to pass through the scar are unclear. Here, we used immunohistochemistry to examine the expression of two chondroitin sulfates with different sulfation variants at the lesion site in goldfish spinal cord. The intact spinal cord was immunoreactive for both chondroitin sulfate-A (CS-A) and chondroitin sulfate-C (CS-C), and CS-A immunoreactivity overlapped extensively with glial processes positive for glial fibrillary acidic protein. At 1week after inducing the spinal lesion, CS-A immunoreactivity was observed in the cell bodies and extracellular matrix, as well as in glial processes surrounding the lesion center. At 2weeks after the spinal lesion, regenerating axons entering the lesion center overtook the CS-A abundant area. In contrast, at 1week after lesion induction, CS-C immunoreactivity was significantly decreased, and at 2weeks after lesion induction, CS-C immunoreactivity was observed along the regenerating axons entering the lesion center. The present findings suggest that after spinal cord injury in goldfish, chondroitin sulfate proteoglycans are deposited in the extracellular matrix at the lesion site but do not form an impenetrable barrier to the growth of regenerating axons. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Peripheral Inflammation Undermines the Plasticity of the Isolated Spinal Cord

    PubMed Central

    Huie, John R.; Grau, James W.

    2009-01-01

    Peripheral capsaicin treatment induces molecular changes that sensitize the responses of nociceptive neurons in the spinal dorsal horn. The current studies demonstrate that capsaicin also undermines the adaptive plasticity of the spinal cord, rendering the system incapable of learning a simple instrumental task. In these studies, male rats are transected at the second thoracic vertebra and are tested 24 to 48 hours later. During testing, subjects receive shock to one hindleg when it is extended (controllable stimulation). Rats quickly learn to maintain the leg in a flexed position. Rats that have been injected with capsaicin (1% or 3%) in the hindpaw fail to learn, even when tested on the leg contralateral to the injection. This learning deficit lasts at least 24 hours. Interestingly, training with controllable electrical stimulation prior to capsaicin administration protects the spinal cord against the maladaptive effects. Rats pretrained with controllable stimulation do not display a learning deficit or tactile allodynia. Moreover, controllable stimulation, combined with naltrexone, reverses the capsaicin-induced deficit. These data suggest that peripheral inflammation, accompanying spinal cord injuries, might have an adverse effect on recovery. PMID:18298266

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

    PubMed

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

    1990-07-01

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

  20. 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.

  1. Therapeutic horse back riding of a spinal cord injured veteran: a case study.

    PubMed

    Asselin, Glennys; Penning, Julius H; Ramanujam, Savithri; Neri, Rebecca; Ward, Constance

    2012-01-01

    To determine an incomplete spinal cord injured veteran's experience following participation in a therapeutic horseback riding program. Following the establishment of a nationwide therapeutic riding program for America's wounded service veterans in 2007, a Certified Rehabilitation Registered Nurse from the Michael E. DeBakey Veteran Affairs Medical Center worked with an incomplete spinal cord injured veteran who participated in the Horses for Heroes program. This program resulted in many benefits for the veteran, including an increase in balance, muscle strength, and self-esteem. A physical, psychological, and psychosocial benefit of therapeutic horseback riding is shown to have positive results for the spinal cord injured. Therapeutic riding is an emerging field where the horse is used as a tool for physical therapy, emotional growth, and learning. Veterans returning from the Iraq/Afghanistan war with traumatic brain injuries, blast injuries, depression, traumatic amputations, and spinal cord injuries may benefit from this nurse-assisted therapy involving the horse. © 2012 Association of Rehabilitation Nurses.

  2. Anaplastic astrocytoma in the spinal cord of an African pygmy hedgehog (Atelerix albiventris).

    PubMed

    Gibson, C J; Parry, N M A; Jakowski, R M; Eshar, D

    2008-11-01

    A 2-year-old, female hedgehog presented with an 8-month history of progressive, ascending paresis/paralysis and was tentatively diagnosed with wobbly hedgehog syndrome. She died awaiting further diagnostic tests, and the owners consented to postmortem examination. Grossly, the bladder was large and flaccid and the cervical and lumbar spinal cord were regionally enlarged, light grey, and friable with multifocal hemorrhages. The thoracic spinal cord was grossly normal. Microscopically all regions of the spinal cord had similar changes, although the cervical and lumbar sections were most severely affected. These regions were completely effaced by a moderately cellular infiltration of highly pleomorphic polygonal to spindle shaped cells, mineralization, and necrosis, which were most consistent with anaplastic astrocytoma. The thoracic spinal cord white matter was similarly infiltrated by the neoplastic cells, with perivascular extension into the otherwise normal grey matter. A diagnosis of anaplastic astrocytoma was confirmed using immunohistochemical stains that were positive for glial fibrillary acidic protein and S100.

  3. 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

  4. 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.

  5. 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

  6. Raman spectroscopic investigation of spinal cord injury in a rat model

    NASA Astrophysics Data System (ADS)

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

    2011-02-01

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

  7. [Research progress in the role of aquaproin-4 and inward rectifying potassium channel 4.1 in spinal cord edema].

    PubMed

    Chen, Tiege; Dang, Yuexiu; Wang, Ming; Zhang, Dongliang; Guo, Yongqiang; Zhang, Haihong

    2018-05-28

    Spinal edema is a very important pathophysiological basis for secondary spinal cord injury, which affects the repair and prognosis of spinal cord injury. Aquaporin-4 is widely distributed in various organs of the body, and is highly expressed in the brain and spinal cord. Inward rectifying potassium channel 4.1 is a protein found in astrocytes of central nervous system. It interacts with aquaporins in function. Aquaporin-4 and inward rectifying potassium channel 4.1 play an important role in the formation and elimination of spinal cord edema, inhibition of glial scar formation and promotion of excitotoxic agents exclusion. The distribution and function of aquaporin-4 and inward rectifying potassium channel 4.1 in the central nervous system and their expression after spinal cord injury have multiple effects on spinal edema. Studies of aquaporin-4 and inward rectifying potassium channel 4.1 in the spinal cord may provide new ideas for the elimination and treatment of spinal edema.

  8. Aquaporin-4 in brain and spinal cord oedema.

    PubMed

    Saadoun, S; Papadopoulos, M C

    2010-07-28

    Brain oedema is a major clinical problem produced by CNS diseases (e.g. stroke, brain tumour, brain abscess) and systemic diseases that secondarily affect the CNS (e.g. hyponatraemia, liver failure). The swollen brain is compressed against the surrounding dura and skull, which causes the intracranial pressure to rise, leading to brain ischaemia, herniation, and ultimately death. A water channel protein, aquaporin-4 (AQP4), is found in astrocyte foot processes (blood-brain border), the glia limitans (subarachnoid cerebrospinal fluid-brain border) and ependyma (ventricular cerebrospinal fluid-brain border). Experiments using mice lacking AQP4 or alpha syntrophin (which secondarily downregulate AQP4) showed that AQP4 facilitates oedema formation in diseases causing cytotoxic (cell swelling) oedema such as cerebral ischaemia, hyponatraemia and meningitis. In contrast, AQP4 facilitates oedema elimination in diseases causing vasogenic (vessel leak) oedema and therefore AQP4 deletion aggravates brain oedema produced by brain tumour and brain abscess. AQP4 is also important in spinal cord oedema. AQP4 deletion was associated with less cord oedema and improved outcome after compression spinal cord injury in mice. Here we consider the possible routes of oedema formation and elimination in the injured cord and speculate about the role of AQP4. Finally we discuss the role of AQP4 in neuromyelitis optica (NMO), an inflammatory demyelinating disease that produces oedema in the spinal cord and optic nerves. NMO patients have circulating AQP4 IgG autoantibody, which is now used for diagnosing NMO. We speculate how NMO-IgG might produce CNS inflammation, demyelination and oedema. Since AQP4 plays a key role in the pathogenesis of CNS oedema, we conclude that AQP4 inhibitors and activators may reduce CNS oedema in many diseases. Copyright (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. 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.

  10. Therapeutic potential of spinal cord stimulation for gastrointestinal motility disorders: a preliminary rodent study.

    PubMed

    Song, G-Q; Sun, Y; Foreman, R D; Chen, J D Z

    2014-03-01

    Spinal cord electrical stimulation (SCS) has been applied for the management of chronic pain. Most of studies have revealed a decrease in sympathetic activity with SCS. The aim of this study was to investigate the effects and mechanisms of SCS on gastrointestinal (GI) motility in healthy and diabetic rats. Male rats chronically implanted with a unipolar electrode at T9/T10 were studied. The study included four experiments to assess the effects of SCS on (1) gastric tone; (2) gastric emptying of liquids and intestinal transit; (3) gastric emptying of solids; and (4) sympathovagal balance in healthy rats and/or in Streptozotocin (STZ)-induced diabetic rat. (1) Spinal cord stimulation intensity dependently increased gastric tone in healthy rats. The gastric volume was 0.97 ± 0.15 mL at baseline, and decreased to 0.92 ± 0.16 mL with SCS of the 30% motor threshold (MT; p = 0.13 vs baseline), 0.86 ± 0.14 mL with 60% MT (p = 0.045 vs baseline), and 0.46 ± 0.19 mL with 90% MT (p = 0.0050 vs baseline). (2) Spinal cord stimulation increased gastric emptying of liquids by about 17% and accelerated small intestinal transit by about 20% in healthy rats (p < 0.001). (3) Spinal cord stimulation accelerated gastric emptying of solids by about 24% in healthy rats and by about 78% in diabetic rats. (4) Spinal cord stimulation decreased sympathetic activity (1.13 ± 0.18 vs 0.68 ± 0.09, p < 0.04) and sympathovagal balance (0.51 ± 0.036 vs 0.40 ± 0.029, p = 0.028). Spinal cord stimulation accelerates gastric emptying of liquids and solids, and intestinal transit, probably by inhibiting the sympathetic activity. Spinal cord stimulation may have a therapeutic potential for treating GI motility disorders. © 2013 John Wiley & Sons Ltd.

  11. Elevated Levels of Calcitonin Gene-Related Peptide in Upper Spinal Cord Promotes Sensitization of Primary Trigeminal Nociceptive Neurons

    PubMed Central

    Cornelison, Lauren E.; Hawkins, Jordan L.; Durham, Paul L.

    2016-01-01

    Orofacial pain conditions including temporomandibular joint disorder and migraine are characterized by peripheral and central sensitization of trigeminal nociceptive neurons. Although calcitonin gene-related peptide (CGRP) is implicated in the development of central sensitization, the pathway by which elevated spinal cord CGRP levels promote peripheral sensitization of primary trigeminal nociceptive neurons is not well understood. The goal of this study was to investigate the role of CGRP in promoting bidirectional signaling within the trigeminal system to mediate sensitization of primary trigeminal ganglion nociceptive neurons. Adult male Sprague Dawley rats were injected in the upper spinal cord with CGRP or co-injected with the receptor antagonist CGRP8-37 or KT 5720, an inhibitor of protein kinase A (PKA). Nocifensive head withdrawal response to mechanical stimulation of trigeminal nerves was investigated using von Frey filaments. Expression of PKA, GFAP, and Iba1 in the spinal cord and P-ERK in the trigeminal ganglion was studied using immunohistochemistry. Some animals were co-injected intracisternally with CGRP and Fast Blue dye and trigeminal ganglion imaged using fluorescent microscopy. Intracisternal CGRP increased nocifensive responses to mechanical stimulation when compared to control levels. Co-injection of CGRP8-37 or KT 5720 with CGRP inhibited the nocifensive response. CGRP stimulated expression of PKA and GFAP in the spinal cord, and P-ERK in trigeminal ganglion neurons. Seven days post injection, Fast Blue was observed in trigeminal ganglion neurons and satellite glial cells. Our results demonstrate that elevated levels of CGRP in the upper spinal cord promote sensitization of primary trigeminal nociceptive neurons via a mechanism that involves activation of PKA centrally and P-ERK in trigeminal ganglion neurons. Our findings provide evidence of bidirectional signaling within the trigeminal system that can facilitate increased neuron

  12. Exercise modulates chloride homeostasis after spinal cord injury.

    PubMed

    Côté, Marie-Pascale; Gandhi, Sapan; Zambrotta, Marina; Houlé, John D

    2014-07-02

    Activity-based therapies are routinely integrated in spinal cord injury (SCI) rehabilitation programs because they result in a reduction of hyperreflexia and spasticity. However, the mechanisms by which exercise regulates activity in spinal pathways to reduce spasticity and improve functional recovery are poorly understood. Persisting alterations in the action of GABA on postsynaptic targets is a signature of CNS injuries, including SCI. The action of GABA depends on the intracellular chloride concentration, which is determined largely by the expression of two cation-chloride cotransporters (CCCs), KCC2 and NKCC1, which serve as chloride exporters and importers, respectively. We hypothesized that the reduction in hyperreflexia with exercise after SCI relies on a return to chloride homeostasis. Sprague Dawley rats received a spinal cord transection at T12 and were assigned to SCI-7d, SCI-14d, SCI-14d+exercise, SCI-28d, SCI-28d+exercise, or SCI-56d groups. During a terminal experiment, H-reflexes were recorded from interosseus muscles after stimulation of the tibial nerve and the low-frequency-dependent depression (FDD) was assessed. We provide evidence that exercise returns spinal excitability and levels of KCC2 and NKCC1 toward normal levels in the lumbar spinal cord. Acutely altering chloride extrusion using the KCC2 blocker DIOA masked the effect of exercise on FDD, whereas blocking NKCC1 with bumetanide returned FDD toward intact levels after SCI. Our results indicate that exercise contributes to reflex recovery and restoration of endogenous inhibition through a return to chloride homeostasis after SCI. This lends support for CCCs as part of a pathway that could be manipulated to improve functional recovery when combined with rehabilitation programs. Copyright © 2014 the authors 0270-6474/14/348976-12$15.00/0.

  13. Overcoming the Practical Barriers to Spinal Cord Cell Transplantation for ALS

    DTIC Science & Technology

    2012-10-01

    ABSTRACT: This grant will provide critical data on tolerance and toxicity of cell dosing and numbers of permissible spinal cord injections. Rigorous...Surgical Technique) will provide critical data on tolerance and toxicity of cell dosing and numbers of permissible spinal cord injections. Aim 2 (Graft...connected to a rigid needle of the same gauge as the floating cannula one – Figure 7) using the maximum volume/number of injections could result in

  14. Spinal Cord Injury Causes Chronic Liver Pathology in Rats

    PubMed Central

    Sauerbeck, Andrew D.; Laws, J. Lukas; Bandaru, Veera V.R.; Popovich, Phillip G.; Haughey, Norman J.

    2015-01-01

    Abstract Traumatic spinal cord injury (SCI) causes major disruption to peripheral organ innervation and regulation. Relatively little work has investigated these post-SCI systemic changes, however, despite considerable evidence that multiple organ system dysfunction contributes to chronic impairments in health. Because metabolic dysfunction is common after SCI and the liver is a pivotal site for metabolic homeostasis, we sought to determine if liver pathology occurs as a result of SCI in a rat spinal contusion model. Histologic evidence showed excess lipid accumulation in the liver for at least 21 days post-injury after cervical or midthoracic SCI. Lipidomic analysis revealed an acute increase in hepatic ceramides as well as chronically elevated lactosylceramide. Post-SCI hepatic changes also included increased proinflammatory gene expression, including interleukin (IL)-1α, IL-1β, chemokine ligand-2, and tumor necrosis factor-α mRNA. These were coincident with increased CD68+ macrophages in the liver through 21 days post-injury. Serum alanine transaminase, used clinically to detect liver damage, was significantly increased at 21 days post-injury, suggesting that early metabolic and inflammatory damage preceded overt liver pathology. Surprisingly, liver inflammation was even detected after lumbar SCI. Collectively, these results suggest that SCI produces chronic liver injury with symptoms strikingly similar to those of nonalcoholic steatohepatitis (fatty liver disease). These clinically significant hepatic changes after SCI are known to contribute to systemic inflammation, cardiovascular disease, and metabolic syndrome, all of which are more prevalent in persons with SCI. Targeting acute and prolonged hepatic pathology may improve recovery and reduce long-term complications after SCI. PMID:25036371

  15. Baclofen or nNOS inhibitor affect molecular and behavioral alterations evoked by traumatic spinal cord injury in rat spinal cord.

    PubMed

    Kisucká, Alexandra; Hricová, Ľudmila; Pavel, Jaroslav; Strosznajder, Joanna B; Chalimoniuk, Malgorzata; Langfort, Jozef; Gálik, Ján; Maršala, Martin; Radoňak, Jozef; Lukáčová, Nadežda

    2015-06-01

    The loss of descending control after spinal cord injury (SCI) and incessant stimulation of Ia monosynaptic pathway, carrying proprioceptive impulses from the muscles and tendons into the spinal cord, evoke exaggerated α-motoneuron activity leading to increased reflex response. Previous results from our laboratory have shown that Ia monosynaptic pathway is nitrergic. The aim of this study was to find out whether nitric oxide produced by neuronal nitric oxide synthase (nNOS) plays a role in setting the excitability of α-motoneurons after thoracic spinal cord transection. We tested the hypothesis that the inhibition of nNOS in α-motoneurons after SCI could have a neuroprotective effect on reflex response. Rats underwent spinal cord transection at Th10 level followed by 7, 10, and 14 days of survival. The animals were treated with Baclofen (a gamma aminobutyric acid B receptor agonist, 3 μg/two times per day/intrathecally) applied for 3 days from the seventh day after transection; N-nitro-l-arginine (NNLA) (nNOS blocator) applied for the first 3 days after injury (20 mg/kg per day, intramuscularly); NNLA and Baclofen; or NNLA (60 mg/kg/day, single dose) applied on the 10th day after transection. We detected the changes in the level of nNOS protein, nNOS messenger RNA, and nNOS immunoreactivity. To investigate the reflex response to heat-induced stimulus, tail-flick test was monitored in treated animals up to 16 days after SCI. Our data indicate that Baclofen therapy is more effective than the combined treatment with NNLA and Baclofen therapy. The single dose of NNLA (60 mg/kg) applied on the 10th day after SCI or Baclofen therapy reduced nNOS expression in α-motoneurons and suppressed symptoms of increased reflex activity. The results clearly show that increased nNOS expression in α-motoneurons after SCI may be pharmacologically modifiable with Baclofen or bolus dose of nNOS blocker. Copyright © 2015. Published by Elsevier Inc.

  16. Investigation of Microbiota Alterations and Intestinal Inflammation Post-Spinal Cord Injury in Rat Model.

    PubMed

    O'Connor, Gregory; Jeffrey, Elisabeth; Madorma, Derik; Marcillo, Alexander; Abreu, Maria T; Deo, Sapna K; Dietrich, W Dalton; Daunert, Sylvia

    2018-06-07

    Although there has been a significant amount of research focused on the pathophysiology of spinal cord injury (SCI), there is limited information on the consequences of SCI on remote organs. SCI can produce significant effects on a variety of organ systems, including the gastrointestinal tract. Patients with SCI often suffer from severe, debilitating bowel dysfunction in addition to their physical disabilities, which is of major concern for these individuals because of the adverse impact on their quality of life. Herein, we report on our investigation into the effects of SCI and subsequent antibiotic treatment on the intestinal tissue and microbiota. For that, we used a thoracic SCI rat model and investigated changes to the microbiota, proinflammatory cytokine levels, and bacterial communication molecule levels post-injury and gentamicin treatment for 7 days. We discovered significant changes, the most interesting being the differences in the gut microbiota beta diversity of 8-week SCI animals compared to control animals at the family, genus, and species level. Specifically, 35 operational taxonomic units were enriched in the SCI animal group and three were identified at species level; Lactobacillus intestinalis, Clostridium disporicum, and Bifidobacterium choerinum. In contrast, Clostridium saccharogumia was identified as depleted in the SCI animal group. Proinflammatory cytokines interleukin (IL)-12, macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor alpha were found to be significantly elevated in intestinal tissue homogenate 4 weeks post-SCI compared to 8-weeks post-injury. Further, levels of IL-1β, IL-12, and MIP-2 significantly correlated with changes in beta diversity 8-weeks post-SCI. Our data provide a greater understanding of the early effects of SCI on the microbiota and gastrointestinal tract, highlighting the need for further investigation to elucidate the mechanism underlying these effects.

  17. The spinal cord and its roots according to Galen.

    PubMed

    Viale, Giuseppe L

    2004-06-01

    Galen's methodological approach to medicine anticipated modern rules. His experiments on the spinal cord contributed greatly to our knowledge of this structure by reporting the variegated pattern of neurological impairment after sectioning at different levels. His approach to injuries of the spinal roots and peripheral nerves documents both diagnostic skill and intellectual honesty.

  18. Impact of Voice and Communication Deficits for Individuals with Cervical Spinal Cord Injury Living in the Community

    ERIC Educational Resources Information Center

    Ward, Elizabeth C.; Jarman, Leigh; Cornwell, Petrea L.; Amsters, Delena I.

    2016-01-01

    Background: Post-spinal cord injury (SCI), individuals may exhibit mild to moderate impairments in aspects of speech influenced by impaired respiratory support. However, limited research has been conducted into the impact of these impairments on activity and participation when living in the community. Aims: To examine the nature and extent of…

  19. The changing nature of admissions to a spinal cord injury center: violence on the rise.

    PubMed

    Farmer, J C; Vaccaro, A R; Balderston, R A; Albert, T J; Cotler, J

    1998-10-01

    The purpose of this study was to analyze changing etiologies for admission to a spinal cord injury center. This study was designed to retrospectively analyze the etiology of admissions to a spinal cord injury center during a 15-year period, specifically gunshot versus nongunshot wound injuries. Gunshot wounds are a well-recognized cause of spinal cord injury. In some centers, up to 52% of admissions are due to this, and these trends are believed to be increasing. All patients with spinal cord injury admitted to our center between 1979 and 1993 were analyzed. Frequencies of specific etiologies were determined and then comparisons were made between gunshot wound and nongunshot wound groups. Factors analyzed included age, male/female ratio, ethnic make-up, marital status, employment status, level of injury, and neurologic status. One thousand eight hundred seventeen patients were included. Overall, gunshot wound spinal cord injuries compromised 16.9% of injuries. A clear trend of increasing numbers of admissions was seen between 1984 and 1993 because of this. Gunshot wounds and nongunshot wounds differed dramatically in terms of age, ethnic make-up, marital status, employment status, and neurologic status. Cost attributed to treating gunshot wound injuries at our center for 1993 was 5.4 million dollars. Gunshot wounds as a cause of spinal cord injury are increasing at an alarming rate. The demographics of the gunshot wounds and nongunshot wound spine cord injuries differ significantly.

  20. Management of acute traumatic spinal cord injuries.

    PubMed

    Shank, C D; Walters, B C; Hadley, M N

    2017-01-01

    Acute traumatic spinal cord injury (SCI) is a devastating disease process affecting tens of thousands of people across the USA each year. Despite the increase in primary prevention measures, such as educational programs, motor vehicle speed limits, automobile running lights, and safety technology that includes automobile passive restraint systems and airbags, SCIs continue to carry substantial permanent morbidity and mortality. Medical measures implemented following the initial injury are designed to limit secondary insult to the spinal cord and to stabilize the spinal column in an attempt to decrease devastating sequelae. This chapter is an overview of the contemporary management of an acute traumatic SCI patient from the time of injury through the stay in the intensive care unit. We discuss initial triage, immobilization, and transportation of the patient by emergency medical services personnel to a definitive treatment facility. Upon arrival at the emergency department, we review initial trauma protocols and the evidence-based recommendations for radiographic evaluation of the patient's vertebral column. Finally, we outline closed cervical spine reduction and various aggressive medical therapies aimed at improving neurologic outcome. © 2017 Elsevier B.V. All rights reserved.

  1. 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.

  2. A new co-ultramicronized composite including palmitoylethanolamide and luteolin to prevent neuroinflammation in spinal cord injury.

    PubMed

    Paterniti, Irene; Impellizzeri, Daniela; Di Paola, Rosanna; Navarra, Michele; Cuzzocrea, Salvatore; Esposito, Emanuela

    2013-07-23

    It has recently been demonstrated that palmitoylethanolamide (PEA), an endogenous lipid amide belonging to the N-acylethanolamine family, exerts neuroprotection in central nervous system (CNS) pathologies. In recent studies, we have demonstrated that treatment with PEA significantly reduced inflammatory secondary events associated with spinal cord injury (SCI). Since oxidative stress is considered to play an important role in neuroinflammatory disorders, in the present work we studied a new composite, a formulation including PEA and the antioxidant compound luteolin (Lut), subjected to an ultramicronization process, co-ultraPEALut. We investigated the effect of co-ultraPEALut (in the respective fixed doses of 10:1 in mass) in both an ex vivo organotypic spinal cord culture model and an in vivo model of SCI. For the organotypic cultures, spinal cords were prepared from mice at postnatal day 6 and were cut into transverse slices of 400 μm thickness to generate the lumbar organotypic slice cultures. After 7 days of culturing, the slices were mechanically injured onto the center of the slice and the co-ultraPEALut was applied at different concentrations (0.00009, 0.0009 and 0.009 g/l) 1 hour before damage. For in vivo studies, SCI was induced in mice through spinal cord compression by the application of vascular clips (force of 24 g) to the dura via a four-level T5 to T8 laminectomy, and co-ultraPEALut (1 mg/kg ip) was administered at 1 and 6 hours after SCI. At 24 hours after SCI, mice were sacrificed and the spinal cords were collected for further evaluation. Additional animals were treated similarly and sacrificed 10 days after SCI. Pretreatment with co-ultraPEALut significantly reduced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in a concentration-dependent manner, restored neuronal nitric oxide synthase (nNOS) expression at all three tested concentrations, and protected cells by cell death (MTT assay) in spinal cord organotypic

  3. A new co-ultramicronized composite including palmitoylethanolamide and luteolin to prevent neuroinflammation in spinal cord injury

    PubMed Central

    2013-01-01

    ) in spinal cord organotypic cultures. Moreover, we demonstrated in vivo that co-ultraPEALut 1 mg/kg reduced the severity of trauma induced by compression and improved the motor activity evaluated at 10 days post-injury. Conclusion The present study demonstrates that the protective effect of PEA on SCI-associated neuroinflammation could be improved by co-ultramicronization with Lut possibly due to its antioxidant properties. PMID:23880066

  4. Vascular dysfunctions following spinal cord injury

    PubMed Central

    Popa, F; Grigorean, VT; Onose, G; Sandu, AM; Popescu, M; Burnei, G; Strambu, V; Sinescu, C

    2010-01-01

    The aim of this article is to analyze the vascular dysfunctions occurring after spinal cord injury (SCI). Vascular dysfunctions are common complications of SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. Neuroanatomy and physiology of autonomic nervous system, sympathetic and parasympathetic, is reviewed. SCI implies disruption of descendent pathways from central centers to spinal sympathetic neurons, originating in intermediolateral nuclei of T1–L2 cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant vascular dysfunction. Spinal shock occurs during the acute phase following SCI and it is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe arterial hypotension and bradycardia. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Arterial hypotension with orthostatic hypotension occurs in both acute and chronic phases. The etiology is multifactorial. We described a few factors influencing the orthostatic hypotension occurrence in SCI: sympathetic nervous system dysfunction, low plasma catecholamine levels, rennin–angiotensin–aldosterone activity, peripheral alpha–adrenoceptor hyperresponsiveness, impaired function of baroreceptors, hyponatremia and low plasmatic volume, cardiovascular deconditioning, morphologic changes in sympathetic neurons, plasticity within spinal circuits, and motor deficit leading to loss of skeletal muscle pumping activity. Additional associated cardiovascular concerns in SCI, such as

  5. 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.

  6. 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

  7. Distribution of syringomyelia along the entire spinal cord in clinically affected Cavalier King Charles Spaniels.

    PubMed

    Loderstedt, Shenja; Benigni, Livia; Chandler, Kate; Cardwell, Jacqueline M; Rusbridge, Clare; Lamb, Christopher R; Volk, Holger A

    2011-12-01

    Chiari-like malformation (CM) and syringomyelia (SM) is an important disease complex in the Cavalier King Charles Spaniel (CKCS) but data about the anatomical distribution of SM along the spinal cord are lacking in veterinary medicine. The objective of this study was to define the anatomic distribution of SM in CKCS clinically affected by CM/SM. Magnetic resonance imaging (MRI) of the brain and the entire spinal cord of 49 dogs was performed and different morphological parameters compared. Syrinx formation was present in the C1-C4 region and in other parts of the spinal cord. The maximal dorsoventral syrinx size can occur in any region of the spinal cord and the total syrinx size was positively correlated with age. Seventy-six per cent of CKCS with a cranial cervical syrinx also have a syrinx affecting more caudal spinal cord regions. MRI restricted to the cervical region may underestimate the extent of SM and the severity of the disease process in the majority of dogs. Copyright © 2010 Elsevier Ltd. All rights reserved.

  8. Brain and spinal cord interaction: a dietary curcumin derivative counteracts locomotor and cognitive deficits after brain trauma.

    PubMed

    Wu, Aiguo; Ying, Zhe; Schubert, David; Gomez-Pinilla, Fernando

    2011-05-01

    In addition to cognitive dysfunction, locomotor deficits are prevalent in traumatic brain injured (TBI) patients; however, it is unclear how a concussive injury can affect spinal cord centers. Moreover, there are no current efficient treatments that can counteract the broad pathology associated with TBI. The authors have investigated potential molecular basis for the disruptive effects of TBI on spinal cord and hippocampus and the neuroprotection of a curcumin derivative to reduce the effects of experimental TBI. The authors performed fluid percussion injury (FPI) and then rats were exposed to dietary supplementation of the curcumin derivative (CNB-001; 500 ppm). The curry spice curcumin has protective capacity in animal models of neurodegenerative diseases, and the curcumin derivative has enhanced brain absorption and biological activity. The results show that FPI in rats, in addition to reducing learning ability, reduced locomotor performance. Behavioral deficits were accompanied by reductions in molecular systems important for synaptic plasticity underlying behavioral plasticity in the brain and spinal cord. The post-TBI dietary supplementation of the curcumin derivative normalized levels of BDNF, and its downstream effectors on synaptic plasticity (CREB, synapsin I) and neuronal signaling (CaMKII), as well as levels of oxidative stress-related molecules (SOD, Sir2). These studies define a mechanism by which TBI can compromise centers related to cognitive processing and locomotion. The findings also show the influence of the curcumin derivative on synaptic plasticity events in the brain and spinal cord and emphasize the therapeutic potential of this noninvasive dietary intervention for TBI.

  9. Modules in the brain stem and spinal cord underlying motor behaviors

    PubMed Central

    Cheung, Vincent C. K.; Bizzi, Emilio

    2011-01-01

    Previous studies using intact and spinalized animals have suggested that coordinated movements can be generated by appropriate combinations of muscle synergies controlled by the central nervous system (CNS). However, which CNS regions are responsible for expressing muscle synergies remains an open question. We address whether the brain stem and spinal cord are involved in expressing muscle synergies used for executing a range of natural movements. We analyzed the electromyographic (EMG) data recorded from frog leg muscles before and after transection at different levels of the neuraxis—rostral midbrain (brain stem preparations), rostral medulla (medullary preparations), and the spinal-medullary junction (spinal preparations). Brain stem frogs could jump, swim, kick, and step, while medullary frogs could perform only a partial repertoire of movements. In spinal frogs, cutaneous reflexes could be elicited. Systematic EMG analysis found two different synergy types: 1) synergies shared between pre- and posttransection states and 2) synergies specific to individual states. Almost all synergies found in natural movements persisted after transection at rostral midbrain or medulla but not at the spinal-medullary junction for swim and step. Some pretransection- and posttransection-specific synergies for a certain behavior appeared as shared synergies for other motor behaviors of the same animal. These results suggest that the medulla and spinal cord are sufficient for the expression of most muscle synergies in frog behaviors. Overall, this study provides further evidence supporting the idea that motor behaviors may be constructed by muscle synergies organized within the brain stem and spinal cord and activated by descending commands from supraspinal areas. PMID:21653716

  10. 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

  11. Characterization of Proliferating Neural Progenitors after Spinal Cord Injury in Adult Zebrafish

    PubMed Central

    Hui, Subhra Prakash; Nag, Tapas Chandra; Ghosh, Sukla

    2015-01-01

    Zebrafish can repair their injured brain and spinal cord after injury unlike adult mammalian central nervous system. Any injury to zebrafish spinal cord would lead to increased proliferation and neurogenesis. There are presences of proliferating progenitors from which both neuronal and glial loss can be reversed by appropriately generating new neurons and glia. We have demonstrated the presence of multiple progenitors, which are different types of proliferating populations like Sox2+ neural progenitor, A2B5+ astrocyte/ glial progenitor, NG2+ oligodendrocyte progenitor, radial glia and Schwann cell like progenitor. We analyzed the expression levels of two common markers of dedifferentiation like msx-b and vimentin during regeneration along with some of the pluripotency associated factors to explore the possible role of these two processes. Among the several key factors related to pluripotency, pou5f1 and sox2 are upregulated during regeneration and associated with activation of neural progenitor cells. Uncovering the molecular mechanism for endogenous regeneration of adult zebrafish spinal cord would give us more clues on important targets for future therapeutic approach in mammalian spinal cord repair and regeneration. PMID:26630262

  12. Extraction of motor activity from the cervical spinal cord of behaving rats

    NASA Astrophysics Data System (ADS)

    Prasad, Abhishek; Sahin, Mesut

    2006-12-01

    Injury at the cervical region of the spinal cord results in the loss of the skeletal muscle control from below the shoulders and hence causes quadriplegia. The brain-computer interface technique is one way of generating a substitute for the lost command signals in these severely paralyzed individuals using the neural signals from the brain. In this study, we are investigating the feasibility of an alternative method where the volitional signals are extracted from the cervical spinal cord above the point of injury. A microelectrode array assembly was implanted chronically at the C5-C6 level of the spinal cord in rats. Neural recordings were made during the face cleaning behavior with forelimbs as this task involves cyclic forelimb movements and does not require any training. The correlation between the volitional motor signals and the elbow movements was studied. Linear regression technique was used to reconstruct the arm movement from the rectified-integrated version of the principal neural components. The results of this study demonstrate the feasibility of extracting the motor signals from the cervical spinal cord and using them for reconstruction of the elbow movements.

  13. 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

  14. Spinal cord injuries among paragliders in Norway.

    PubMed

    Rekand, T; Schaanning, E E; Varga, V; Schattel, U; Gronning, M

    2008-06-01

    A national retrospective descriptive study. To study the clinical effects of spinal cord injuries (SCIs) caused by paragliding accidents in Norway. Spinal cord units at Haukeland University Hospital, Sunnaas Rehabilitation Hospital and St Olav Hospital in Norway. We studied the medical files for nine patients with SCI caused by paragliding accidents to evaluate the circumstances of the accidents, and clinical effects of injury. We obtained the data from hospital patient files at all three spinal units in Norway and crosschecked them through the Norwegian Paragliding Association's voluntary registry for injuries. All patients were hospitalized from 1997 to 2006, eight men and one woman, with mean age 30.7 years. The causes of the accidents were landing problems combined with unexpected wind whirls, technical problems and limited experience with unexpected events. All patients contracted fractures in the thoracolumbal junction of the spine, most commonly at the L1 level. At clinical follow-up, all patients presented clinically incomplete SCI (American Spinal Injury Association impairment scores B-D). Their main health problems differed widely, ranging from urinary and sexual disturbances to neuropathic pain and loss of motor functioning. Only three patients returned to full-time employment after rehabilitation. Paragliding accidents cause spinal fractures predominantly in the thoracolumbal junction with subsequent SCIs and increased morbidity. All patients experienced permanent health problems that influenced daily activities and required long-time clinical follow-up and medical intervention. Better education in landing techniques and understanding of aerodynamics may reduce the risk of paragliding accidents.

  15. Spinal cord injuries in Australian footballers.

    PubMed

    2003-07-01

    Acute spinal cord injury is a serious concern in football, particularly the rugby codes. This Australia-wide study covers the years 1986-1996 and data are compared with those from a previous identical study for 1960-1985. A retrospective review of 80 players with a documented acute spinal cord injury admitted to the six spinal cord injury units in Australia. Personal interview was carried out in 85% of the participants to determine the injury circumstances and the level of compensation. The severity of the neurological deficit and the functional recovery were determined (Frankel grade). The annual incidence of injuries for all codes combined did not change over the study period, but there was some decrease in rugby union and an increase in rugby league. In particular there was a significant decline in the incidence of adult rugby union injuries (P = 0.048). Scrum injuries in union have decreased subsequent to law changes in 1985, particularly in schoolboys, although ruck and maul injuries are increasing; 39% of scrum injuries occurred in players not in their regular position. Tackles were the most common cause of injury in league, with two-on-one tackles accounting for nearly half of these. Schoolboy injuries tended to mirror those in adults, but with a lower incidence. Over half of the players remain wheelchair-dependent, and 10% returned to near-normality. Six players (7.5%) died as a result of their injuries. The rugby codes must be made safer by appropriate preventative strategies and law changes. In particular, attention is necessary for tackle injuries in rugby league and players out of regular position in scrummage. Compensation for injured players is grossly inadequate. There is an urgent need to establish a national registry to analyse these injuries prospectively.

  16. Numb rats walk - a behavioural and fMRI comparison of mild and moderate spinal cord injury.

    PubMed

    Hofstetter, Christoph P; Schweinhardt, Petra; Klason, Tomas; Olson, Lars; Spenger, Christian

    2003-12-01

    Assessment of sensory function serves as a sensitive measure for predicting the functional outcome following spinal cord injury in patients. However, little is known about loss and recovery of sensory function in rodent spinal cord injury models as most tests of sensory functions rely on behaviour and thus motor function. We used functional magnetic resonance imaging (fMRI) to investigate cortical and thalamic BOLD-signal changes in response to limb stimulation following mild or moderate thoracic spinal cord weight drop injury in Sprague-Dawley rats. While there was recovery of close to normal hindlimb motor function as determined by open field locomotor testing following both degrees of injury, recovery of hindlimb sensory function as determined by fMRI and hot plate testing was only seen following mild injury and not following moderate injury. Thus, moderate injury can lead to near normal hindlimb motor function in animals with major sensory deficits. Recovered fMRI signals following mild injury had a partly altered cortical distribution engaging also ipsilateral somatosensory cortex and the cingulate gyrus. Importantly, thoracic spinal cord injury also affected sensory representation of the upper nonaffected limbs. Thus, cortical and thalamic activation in response to forelimb stimulation was significantly increased 16 weeks after spinal cord injury compared to control animals. We conclude that both forelimb and hindlimb cortical sensory representation is altered following thoracic spinal cord injury. Furthermore tests of sensory function that are independent of motor behaviour are needed in rodent spinal cord injury research.

  17. 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.

  18. Beneficial effects of early hemostasis on spinal cord injury in the rat

    PubMed Central

    Fan, H; Chen, K; Duan, L; Wang, Y-Z; Ju, G

    2016-01-01

    Study design: Experimental study. Objectives: To investigate the effect of early hemostasis on spinal cord injury (SCI). Setting: Fourth Military Medical University, Xi'an, China. Methods: Sprague Dawley rats were used. Hematoxylin and eosin (HE) staining was performed to observe hemorrhage at different time points (2, 6, 12, 24 and 48 h) after SCI to determine the time window of hemostatic drug administration (n=3 per time point). Three different concentrations of Etamsylate (0.025, 0.05 and 0.1 g kg−1) were administered immediately and 5 and 10 h after SCI to evaluate the effective dosage (n=6 per group). Another 82 rats were then randomly divided into two groups, Etamsylate group (0.1 g kg−1, n=41) and glucose control group (n=41). Nissl staining was performed to observe neurons at 10 days post injury. Immunohistochemistry, western blot and quantitative real-time PCR were performed to detect tissue necrosis at 7 d.p.i., the activation of astrocytes and microglia/macrophages and lesion cavity at 10 d.p.i. Basso–Beattie–Bresnahan scoring and rump height index assay were used to examine locomotion recovery. Results: Early hemostasis reduced the lesion area and tissue necrosis, enhanced neuronal survival, alleviated the activation of microglia/macrophages and astrocytes and facilitated functional recovery after spinal cord contusion in rats. Early hemostasis decreased hemorrhage area and lesion area after spinal cord transection in rats. Conclusion: The present study demonstrated that early hemostasis has beneficial effects on SCI in the rat. It has the potential to be translated into clinical practice. PMID:27137123

  19. Minocycline Effectively Protects the Rabbit's Spinal Cord From Aortic Occlusion-Related Ischemia.

    PubMed

    Drenger, Benjamin; Fellig, Yakov; Ben-David, Dror; Mintz, Bella; Idrees, Suhel; Or, Omer; Kaplan, Leon; Ginosar, Yehuda; Barzilay, Yair

    2016-04-01

    To identify the minocycline anti-inflammatory and antiapoptotic mechanisms through which it is believed to exert spinal cord protection during aortic occlusion in the rabbit model. An animal model of aortic occlusion-related spinal cord ischemia. Randomized study with a control group and pre-ischemia and post-ischemia escalating doses of minocycline to high-dose minocycline in the presence of either hyperglycemia, a pro-apoptotic maneuver, or wortmannin, a specific phosphatidylinositol 3-kinase antagonist. Tertiary medical center and school of medicine laboratory. Laboratory animals-rabbits. Balloon obstruction of infrarenal aorta introduced via femoral artery incision. Severe hindlimb paralysis (mean Tarlov score 0.36±0.81 out of 3) was observed in all the control group animals (9 of 11 with paraplegia and 2 of 11 with paraparesis) compared with 11 of 12 neurologically intact animals (mean Tarlov score 2.58±0.90 [p = 0.001 compared with control]) in the high-dose minocycline group. This protective effect was observed partially during a state of hyperglycemia and was completely abrogated by wortmannin. Minocycline administration resulted in higher neurologic scores (p = 0.003) and a shift to viable neurons and more apoptotic-stained nuclei resulting from reduced necrosis (p = 0.001). In a rabbit model of infrarenal aortic occlusion, minocycline effectively reduced paraplegia by increasing the number of viable neurons in a dose-dependent manner. Its action was completely abrogated by inhibiting the phosphatidylinositol 3-kinase pathway and was inhibited partially by the pro-apoptotic hyperglycemia maneuver, indicating that the activation of cell salvage pathways and mitochondrial sites are possible targets of minocycline action in an ischemic spinal cord. Copyright © 2016. Published by Elsevier Inc.

  20. 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.

  1. Religiosity and Spirituality among Persons with Spinal Cord Injury: Attitudes, Beliefs, and Practices

    ERIC Educational Resources Information Center

    Marini, Irmo; Glover-Graf, Noreen M.

    2011-01-01

    A total of 157 persons with spinal cord injury completed the "Spirituality and Spinal Cord Injury Survey" in relation to their spiritual and/or religious attitudes, beliefs, and practices in terms of adapting to their disability. Factor analysis accounting for 69% of the variance revealed four factors related to Spiritual Help and Improvement…

  2. 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

  3. 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

  4. [Effect of M8046 on expression of COX-2/PGE2 in spinal cord and DRG in rats with neuropathic pain].

    PubMed

    Ou, Guo-Kun; Wang, Rui-Xian; Li, Jia-Jia; Cao, Hong; Lian, Qing-Quan; Li, Jun

    2013-03-01

    To investigate the effects of glucocorticoid receptor antagonist-M8046 on the behavior and the cyclooxygenase-2/prostaglandin E2( COX-2/PGE2) expression in spinal cord dorsal horn and dorsal root ganglia (DRG) in chronic constrictive injury (CCI) rats. One hundred and forty-four male SD rats were randomly divided into 4 groups, 36 rats in each group: Sham operation group (Sham), chronic constrictive group (CCI), M8046 treated group (M8046) and solvent controlled group (Sc). M8046 3 mg/(kg x d) intraperitoneal injection was given after operation in group M8046. Paw thennal withdrawal (PTWL) and paw mechanical withdrawal threshold (PMWT) of rats were measured on 2 pre-operative and 1, 3, 7, 10, 14 post-operative days. The spinal cord and L15 DRG of the operated side was removed at 3, 7, 14 days after surgery. The change of COX-2 and PGE2 expression was determined by immunohistochemical staining and ELISA separately. PTWL and PMWT in CCI group were significantly lower than those in Sham group on every post-operative day (P < 0.05). PTWL and PMWT in M8046 group were significantly higher than those in CCI group on 7, 10, 14 post-operative day (P < 0.05). In spinal dorsal horn, the level of COX-2 and PGE2 expression in CCI group was significantly higher than that in Sham group (P < 0.05). M8046 could significantly attenuate the activation of COX-2 and PGE2 induced by CCI (P < 0.05). The expression of COX-2 and PGE2 in DRG was similar to that in spinal dorsal horn. The effects of M8046 ameliorate the CCI-induced neuropathic pain may be related to attenuate the expression of COX-2 and PGE2 in spinal cord and DRG.

  5. 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

  6. 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

  7. 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

  8. Spinal Cord Tolerance to Single-Fraction Partial-Volume Irradiation: A Swine Model

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

    Medin, Paul M., E-mail: Paul.medin@utsouthwestern.ed; Foster, Ryan D.; Kogel, Albert J. van der

    2011-01-01

    Purpose: To determine the spinal cord tolerance to single-fraction, partial-volume irradiation in swine. Methods and Materials: A 5-cm-long cervical segment was irradiated in 38-47-week-old Yucatan minipigs using a dedicated, image-guided radiosurgery linear accelerator. The radiation was delivered to a cylindrical volume approximately 5 cm in length and 2 cm in diameter that was positioned lateral to the cervical spinal cord, resulting in a dose distribution with the 90%, 50%, and 10% isodose lines traversing the ipsilateral, central, and contralateral spinal cord, respectively. The dose was prescribed to the 90% isodose line. A total of 26 pigs were stratified into eightmore » dose groups of 12-47 Gy. The mean maximum spinal cord dose was 16.9 {+-} 0.1, 18.9 {+-} 0.1, 21.0 {+-} 0.1, 23.0 {+-} 0.2, and 25.3 {+-} 0.3 Gy in the 16-, 18-, 20-, 22-, and 24-Gy dose groups, respectively. The mean percentage of spinal cord volumes receiving {>=}10 Gy for the same groups were 43% {+-} 3%, 48% {+-} 4%, 51% {+-} 2%, 57% {+-} 2%, and 59% {+-} 4%. The study endpoint was motor neurologic deficit determined by a change in gait during a 1-year follow-up period. Results: A steep dose-response curve was observed with a median effective dose for the maximum dose point of 20.0 Gy (95% confidence interval, 18.3-21.7). Excellent agreement was observed between the occurrence of neurologic change and the presence of histologic change. All the minipigs with motor deficits showed some degree of demyelination and focal white matter necrosis on the irradiated side, with relative sparing of the gray matter. The histologic findings were unremarkable in the minipigs with normal neurologic status. Conclusions: Our results have indicated that for a dose distribution with a steep lateral gradient, the pigs had a lower median effective dose for paralysis than has been observed in rats and more closely resembles that for rats, mice, and guinea pigs receiving uniform spinal cord irradiation.« less

  9. Effects of spinal cord stimulation in angina pectoris induced by pacing and possible mechanisms of action.

    PubMed Central

    Mannheimer, C; Eliasson, T; Andersson, B; Bergh, C H; Augustinsson, L E; Emanuelsson, H; Waagstein, F

    1993-01-01

    OBJECTIVE--To investigate the effects of spinal cord stimulation on myocardial ischaemia, coronary blood flow, and myocardial oxygen consumption in angina pectoris induced by atrial pacing. DESIGN--The heart was paced to angina during a control phase and treatment with spinal cord stimulation. Blood samples were drawn from a peripheral artery and the coronary sinus. SETTING--Multidisciplinary pain centre, department of medicine, Ostra Hospital, and Wallenberg Research Laboratory, Sahlgrenska Hospital, Gothenburg, Sweden. SUBJECTS--Twenty patients with intractable angina pectoris, all with a spinal cord stimulator implanted before the study. RESULTS--Spinal cord stimulation increased patients' tolerance to pacing (p < 0.001). At the pacing rate comparable to that producing angina during the control recording, myocardial lactate production during control session turned into extraction (p = 0.003) and, on the electrocardiogram, ST segment depression decreased, time to ST depression increased, and time to recovery from ST depression decreased (p = 0.01; p < 0.05, and p < 0.05, respectively). Spinal cord stimulation also reduced coronary sinus blood flow (p = 0.01) and myocardial oxygen consumption (p = 0.02). At the maximum pacing rate during treatment, all patients experienced anginal pain. Myocardial lactate extraction reverted to production (p < 0.01) and the magnitude and duration of ST segment depression increased to the same values as during control pacing, indicating that myocardial ischaemia during treatment with spinal cord stimulation gives rise to anginal pain. CONCLUSIONS--Spinal cord stimulation has an anti-anginal and anti-ischaemic effect in severe coronary artery disease. These effects seem to be secondary to a decrease in myocardial oxygen consumption. Furthermore, myocardial ischemia during treatment gives rise to anginal pain. Thus, spinal cord stimulation does not deprive the patient of a warning signal. PMID:8400930

  10. [Larsen syndrome: two reports of cases with spinal cord compromise].

    PubMed

    Martín Fernández-Mayoralas, D; Fernández-Jaén, A; Muñoz-Jareño, N; Calleja-Pérez, B; San Antonio-Arce, V; Martínez-Boniche, H

    Larsen syndrome is characterised by untreatable congenital dislocation of multiple body joints, along with marked foot deformities. These patients have a flattened face with a short nose, a broad depressed nasal bridge and a prominent forehead. In this clinical note our aim is to report two cases that coursed with spinal cord compromise. Case 1: an 18-month-old female with congenital dislocation of knees and hips. The patient had a flat face, sunken root of nose, and carp mouth. Magnetic resonance imaging of the spine showed severe cervical kyphosis secondary to malformation and hypoplasia of the cervical vertebral bodies and important compression of the spinal cord. Clinically, there were also signs of upper motor neuron syndrome, which was especially prominent in the lower limbs. Case 2: a 14-year-old male with a characteristic face and dislocation of the head of the radius. The patient presented amyotrophy of the muscles in the right hand and clinical signs of lower motor neuron syndrome due to neuronal damage secondary to spinal malformations. Larsen syndrome is an infrequent osteochondrodysplasia. Alteration of the spine is common and may give rise to spinal cord compression with varying clinical repercussions which require surgical treatment in the early years of the patient's life.

  11. Spinal Cord Excitability and Sprint Performance Are Enhanced by Sensory Stimulation During Cycling

    PubMed Central

    Pearcey, Gregory E. P.; Noble, Steven A.; Munro, Bridget; Zehr, E. Paul

    2017-01-01

    Spinal cord excitability, as assessed by modulation of Hoffmann (H-) reflexes, is reduced with fatiguing isometric contractions. Furthermore, spinal cord excitability is reduced during non-fatiguing arm and leg cycling. Presynaptic inhibition of Ia terminals is believed to contribute to this suppression of spinal cord excitability. Electrical stimulation to cutaneous nerves reduces Ia presynaptic inhibition, which facilitates spinal cord excitability, and this facilitation is present during arm cycling. Although it has been suggested that reducing presynaptic inhibition may prolong fatiguing contractions, it is unknown whether sensory stimulation can alter the effects of fatiguing exercise on performance or spinal cord excitability. Thus, the aim of this experiment was to determine if sensory stimulation can interfere with fatigue-related suppression of spinal cord excitability, and alter fatigue rates during cycling sprints. Thirteen participants randomly performed three experimental sessions that included: unloaded cycling with sensory stimulation (CONTROL + STIM), sprints with sensory stimulation (SPRINT + STIM) and sprints without stimulation (SPRINT). Seven participants also performed a fourth session (CONTROL), which consisted of unloaded cycling. During SPRINT and SPRINT + STIM, participants performed seven, 10 s cycling sprints interleaved with 3 min rest. For CONTROL and CONTROL + STIM, participants performed unloaded cycling for ~30 min. During SPRINT + STIM and CONTROL + STIM, participants received patterned sensory stimulation to nerves of the right foot. H-reflexes and M-waves of the right soleus were evoked by stimulation of the tibial nerve at multiple time points throughout exercise. Sensory stimulation facilitated soleus H-reflexes during unloaded cycling, whereas sprints suppressed soleus H-reflexes. While receiving sensory stimulation, there was less suppression of soleus H-reflexes and slowed reduction in average power output, compared to

  12. Spinal Cord Excitability and Sprint Performance Are Enhanced by Sensory Stimulation During Cycling.

    PubMed

    Pearcey, Gregory E P; Noble, Steven A; Munro, Bridget; Zehr, E Paul

    2017-01-01

    Spinal cord excitability, as assessed by modulation of Hoffmann (H-) reflexes, is reduced with fatiguing isometric contractions. Furthermore, spinal cord excitability is reduced during non-fatiguing arm and leg cycling. Presynaptic inhibition of Ia terminals is believed to contribute to this suppression of spinal cord excitability. Electrical stimulation to cutaneous nerves reduces Ia presynaptic inhibition, which facilitates spinal cord excitability, and this facilitation is present during arm cycling. Although it has been suggested that reducing presynaptic inhibition may prolong fatiguing contractions, it is unknown whether sensory stimulation can alter the effects of fatiguing exercise on performance or spinal cord excitability. Thus, the aim of this experiment was to determine if sensory stimulation can interfere with fatigue-related suppression of spinal cord excitability, and alter fatigue rates during cycling sprints. Thirteen participants randomly performed three experimental sessions that included: unloaded cycling with sensory stimulation ( CONTROL + STIM ), sprints with sensory stimulation ( SPRINT + STIM ) and sprints without stimulation ( SPRINT ). Seven participants also performed a fourth session ( CONTROL ), which consisted of unloaded cycling. During SPRINT and SPRINT + STIM, participants performed seven, 10 s cycling sprints interleaved with 3 min rest. For CONTROL and CONTROL + STIM , participants performed unloaded cycling for ~30 min. During SPRINT + STIM and CONTROL + STIM , participants received patterned sensory stimulation to nerves of the right foot. H-reflexes and M-waves of the right soleus were evoked by stimulation of the tibial nerve at multiple time points throughout exercise. Sensory stimulation facilitated soleus H-reflexes during unloaded cycling, whereas sprints suppressed soleus H-reflexes. While receiving sensory stimulation, there was less suppression of soleus H-reflexes and slowed reduction in average power output, compared

  13. 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

  14. 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.

  15. The collateral network concept: a reassessment of the anatomy of spinal cord perfusion.

    PubMed

    Etz, Christian D; Kari, Fabian A; Mueller, Christoph S; Silovitz, Daniel; Brenner, Robert M; Lin, Hung-Mo; Griepp, Randall B

    2011-04-01

    Prevention of paraplegia after repair of thoracoabdominal aortic aneurysm requires understanding the anatomy and physiology of the spinal cord blood supply. Recent laboratory studies and clinical observations suggest that a robust collateral network must exist to explain preservation of spinal cord perfusion when segmental vessels are interrupted. An anatomic study was undertaken. Twelve juvenile Yorkshire pigs underwent aortic cannulation and infusion of a low-viscosity acrylic resin at physiologic pressures. After curing of the resin and digestion of all organic tissue, the anatomy of the blood supply to the spinal cord was studied grossly and with light and electron microscopy. All vascular structures at least 8 μm in diameter were preserved. Thoracic and lumbar segmental arteries give rise not only to the anterior spinal artery but to an extensive paraspinous network feeding the erector spinae, iliopsoas, and associated muscles. The anterior spinal artery, mean diameter 134 ± 20 μm, is connected at multiple points to repetitive circular epidural arteries with mean diameters of 150 ± 26 μm. The capacity of the paraspinous muscular network is 25-fold the capacity of the circular epidural arterial network and anterior spinal artery combined. Extensive arterial collateralization is apparent between the intraspinal and paraspinous networks, and within each network. Only 75% of all segmental arteries provide direct anterior spinal artery-supplying branches. The anterior spinal artery is only one component of an extensive paraspinous and intraspinal collateral vascular network. This network provides an anatomic explanation of the physiological resiliency of spinal cord perfusion when segmental arteries are sacrificed during thoracoabdominal aortic aneurysm repair. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  16. Spinal Cord Tolerance to Reirradiation With Single-Fraction Radiosurgery: A Swine Model

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

    Medin, Paul M., E-mail: Paul.medin@utsouthwestern.edu; Foster, Ryan D.; Kogel, Albert J. van der

    2012-07-01

    Purpose: This study was performed to determine swine spinal cord tolerance to single-fraction, partial-volume irradiation 1 year after receiving uniform irradiation to 30 Gy in 10 fractions. Methods and Materials: A 10-cm length of spinal cord (C3-T1) was uniformly irradiated to 30 Gy in 10 consecutive fractions and reirradiated 1 year later with a single radiosurgery dose centered within the previously irradiated segment. Radiosurgery was delivered to a cylindrical volume approximately 5 cm in length and 2 cm in diameter, which was positioned laterally to the cervical spinal cord, resulting in a dose distribution with the 90%, 50%, and 10%more » isodose lines traversing the ipsilateral, central, and contralateral spinal cord, respectively. Twenty-three pigs were stratified into six dose groups with mean maximum spinal cord doses of 14.9 {+-} 0.1 Gy (n = 2), 17.1 {+-} 0.3 Gy (n = 3), 19.0 {+-} 0.1 Gy (n = 5), 21.2 {+-} 0.1 Gy (n = 5), 23.4 {+-} 0.2 Gy (n = 5), and 25.4 {+-} 0.4 Gy (n = 3). The mean percentage of spinal cord volumes receiving {>=}10 Gy for the same groups were 34% {+-} 1%, 40% {+-} 1%, 46% {+-} 3%, 52% {+-} 1%, 56 {+-} 3%, and 57% {+-} 1%. The study endpoint was motor neurologic deficit as determined by a change in gait during a 1- year follow-up period. Results: A steep dose-response curve was observed with a 50% incidence of paralysis (ED{sub 50}) for the maximum point dose of 19.7 Gy (95% confidence interval, 17.4-21.4). With two exceptions, histology was unremarkable in animals with normal neurologic status, while all animals with motor deficits showed some degree of demyelination and focal white matter necrosis on the irradiated side, with relative sparing of gray matter. Histologic comparison with a companion study of de novo irradiated animals revealed that retreatment responders had more extensive tissue damage, including infarction of gray matter, only at prescription doses >20 Gy. Conclusion: Pigs receiving spinal radiosurgery 1 year

  17. Spinal cord regeneration: lessons for mammals from non-mammalian vertebrates.

    PubMed

    Lee-Liu, Dasfne; Edwards-Faret, Gabriela; Tapia, Víctor S; Larraín, Juan

    2013-08-01

    Unlike mammals, regenerative model organisms such as amphibians and fish are capable of spinal cord regeneration after injury. Certain key differences between regenerative and nonregenerative organisms have been suggested as involved in promoting this process, such as the capacity for neurogenesis and axonal regeneration, which appear to be facilitated by favorable astroglial, inflammatory and immune responses. These traits provide a regenerative-permissive environment that the mammalian spinal cord appears to be lacking. Evidence for the regenerative nonpermissive environment in mammals is given by the fact that they possess neural stem/progenitor cells, which transplanted into permissive environments are able to give rise to new neurons, whereas in the nonpermissive spinal cord they are unable to do so. We discuss the traits that are favorable for regeneration, comparing what happens in mammals with each regenerative organism, aiming to describe and identify the key differences that allow regeneration. This comparison should lead us toward finding how to promote regeneration in organisms that are unable to do so. Copyright © 2013 Wiley Periodicals, Inc.

  18. Effects of hemorrhagic hypotension on tyrosine concentrations in rat spinal cord and plasma

    NASA Technical Reports Server (NTRS)

    Conlay, L. A.; Maher, T. J.; Roberts, C. H.; Wurtman, R. J.

    1988-01-01

    Tyrosine is the precursor for catecholamine neurotransmitters. When catecholamine-containing neurons are physiologically active (as sympathoadrenal cells are in hypotension), tyrosine administration increases catecholamine synthesis and release. Since hypotension can alter plasma amino acid composition, the effects of an acute hypotensive insult on tyrosine concentrations in plasma and spinal cord were examined. Rats were cannulated and bled until the systolic blood pressure was 50 mmHg, or were kept normotensive for 1 h. Tyrosine and other large neutral amino acids (LNAA) known to compete with tyrosine for brain uptake were assayed in plasma and spinal cord. The rate at which intra-arterial (H-3)tyrosine disappeared from the plasma was also estimated in hemorrhaged and control rats. In plasma of hemorrhaged animals, both the tyrosine concentration and the tyrosine/LNAA ratio was elevated; moreover, the disappearance of (H-3)tyrosine was slowed. Tyrosine concentrations also increased in spinal cords of hemorrhaged-hypotensive rats when compared to normotensive controls. Changes in plasma amino acid patterns may thus influence spinal cord concentrations of amino acid precursors for neurotransmitters during the stress of hemorrhagic shock.

  19. Association of head trauma with cervical spine injury, spinal cord injury, or both.

    PubMed

    Iida, H; Tachibana, S; Kitahara, T; Horiike, S; Ohwada, T; Fujii, K

    1999-03-01

    Links between cervical spine and/or spinal cord injuries and head trauma have not been reported in detail. 188 patients with cervical spine and/or spinal cord injury were divided into two groups, i.e., with upper cervical and mid-lower cervical injury, and compared for head injury. Associated head trauma was investigated in 188 patients with cervical spine and/or spinal cord injuries; 35% had moderate or severe injuries. Brain damage was more frequently observed in patients with upper cervical injury than in those with mid to lower cervical injury. Those patients with upper cervical injury appeared to have an elevated risk of suffering skull base fractures, traumatic subarachnoid hemorrhage, and contusional hemotoma. Approximately one third of patients with cervical spine and/or spinal cord injuries had moderate or severe head injuries. Brain damage was more frequently associated with upper cervical injury. Those patients with upper cervical injury are at greater risk of suffering from skull base fractures and severe intracranial hematomas than those with mid to lower cervical injury.

  20. Expression and Cellular Distribution of Ubiquitin in Response to Injury in the Developing Spinal Cord of Monodelphis domestica

    PubMed Central

    Noor, Natassya M.; Møllgård, Kjeld; Wheaton, Benjamin J.; Steer, David L.; Truettner, Jessie S.; Dziegielewska, Katarzyna M.; Dietrich, W. Dalton; Smith, A. Ian; Saunders, Norman R.

    2013-01-01

    Ubiquitin, an 8.5 kDa protein associated with the proteasome degradation pathway has been recently identified as differentially expressed in segment of cord caudal to site of injury in developing spinal cord. Here we describe ubiquitin expression and cellular distribution in spinal cord up to postnatal day P35 in control opossums (Monodelphis domestica) and in response to complete spinal transection (T10) at P7, when axonal growth through site of injury occurs, and P28 when this is no longer possible. Cords were collected 1 or 7 days after injury, with age-matched controls and segments rostral to lesion were studied. Following spinal injury ubiquitin levels (western blotting) appeared reduced compared to controls especially one day after injury at P28. In contrast, after injury mRNA expression (qRT-PCR) was slightly increased at P7 but decreased at P28. Changes in isoelectric point of separated ubiquitin indicated possible post-translational modifications. Cellular distribution demonstrated a developmental shift between earliest (P8) and latest (P35) ages examined, from a predominantly cytoplasmic immunoreactivity to a nuclear expression; staining level and shift to nuclear staining was more pronounced following injury, except 7 days after transection at P28. After injury at P7 immunostaining increased in neurons and additionally in oligodendrocytes at P28. Mass spectrometry showed two ubiquitin bands; the heavier was identified as a fusion product, likely to be an ubiquitin precursor. Apparent changes in ubiquitin expression and cellular distribution in development and response to spinal injury suggest an intricate regulatory system that modulates these responses which, when better understood, may lead to potential therapeutic targets. PMID:23626776

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  2. 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.

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

    PubMed

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

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

  4. Olfactory Ensheathing Cell Transplantation after a Complete Spinal Cord Transection Mediates Neuroprotective and Immunomodulatory Mechanisms to Facilitate Regeneration

    PubMed Central

    Khankan, Rana R.; Griffis, Khris G.; Haggerty-Skeans, James R.; Zhong, Hui; Roy, Roland R.; Edgerton, V. Reggie

    2016-01-01

    Multiple neural and peripheral cell types rapidly respond to tissue damage after spinal cord injury to form a structurally and chemically inhibitory scar that limits axon regeneration. Astrocytes form an astroglial scar and produce chondroitin sulfate proteoglycans (CSPGs), activate microglia, and recruit blood-derived immune cells to the lesion for debris removal. One beneficial therapy, olfactory ensheathing cell (OEC) transplantation, results in functional improvements and promotes axon regeneration after spinal cord injury. The lack of an OEC-specific marker, however, has limited the investigation of mechanisms underlying their proregenerative effects. We compared the effects of enhanced green fluorescent protein-labeled fibroblast (FB) and OEC transplants acutely after a complete low-thoracic spinal cord transection in adult rats. We assessed the preservation of neurons and serotonergic axons, the levels of inhibitory CSPGs and myelin debris, and the extent of immune cell activation between 1 and 8 weeks postinjury. Our findings indicate that OECs survive longer than FBs post-transplantation, preserve axons and neurons, and reduce inhibitory molecules in the lesion core. Additionally, we show that OECs limit immune-cell activation and infiltration, whereas FBs alter astroglial scar formation and increase immune-cell infiltration and concomitant secondary tissue damage. Administration of cyclosporine-A to enhance graft survival demonstrated that immune suppression can augment OEC contact-mediated protection of axons and neurons during the first 2 weeks postinjury. Collectively, these data suggest that OECs have neuroprotective and immunomodulatory mechanisms that create a supportive environment for neuronal survival and axon regeneration after spinal cord injury. SIGNIFICANCE STATEMENT Spinal cord injury creates physical and chemical barriers to axon regeneration. We used a complete spinal cord transection model and olfactory ensheathing cell (OEC) or

  5. Intraspinal microstimulation and diaphragm activation after cervical spinal cord injury

    PubMed Central

    Mercier, L. M.; Gonzalez-Rothi, E. J.; Streeter, K. A.; Posgai, S. S.; Poirier, A. S.; Fuller, D. D.; Reier, P. J.

    2016-01-01

    Intraspinal microstimulation (ISMS) using implanted electrodes can evoke locomotor movements after spinal cord injury (SCI) but has not been explored in the context of respiratory motor output. An advantage over epidural and direct muscle stimulation is the potential of ISMS to selectively stimulate components of the spinal respiratory network. The present study tested the hypothesis that medullary respiratory activity could be used to trigger midcervical ISMS and diaphragm motor unit activation in rats with cervical SCI. Studies were conducted after acute (hours) and subacute (5–21 days) C2 hemisection (C2Hx) injury in adult rats. Inspiratory bursting in the genioglossus (tongue) muscle was used to trigger a 250-ms train stimulus (100 Hz, 100–200 μA) to the ventral C4 spinal cord, targeting the phrenic motor nucleus. After both acute and subacute injury, genioglossus EMG activity effectively triggered ISMS and activated diaphragm motor units during the inspiratory phase. The ISMS paradigm also evoked short-term potentiation of spontaneous inspiratory activity in the previously paralyzed hemidiaphragm (i.e., bursting persisting beyond the stimulus period) in ∼70% of the C2Hx animals. We conclude that medullary inspiratory output can be used to trigger cervical ISMS and diaphragm activity after SCI. Further refinement of this method may enable “closed-loop-like” ISMS approaches to sustain ventilation after severe SCI. NEW & NOTEWORTHY We examined the feasibility of using intraspinal microstimulation (ISMS) of the cervical spinal cord to evoke diaphragm activity ipsilateral to acute and subacute hemisection of the upper cervical spinal cord of the rat. This proof-of-concept study demonstrated the efficacy of diaphragm activation, using an upper airway respiratory EMG signal to trigger ISMS at the level of the ipsilesional phrenic nucleus during acute and advanced postinjury intervals. PMID:27881723

  6. Association of myelopathy scores with cervical sagittal balance and normalized spinal cord volume: analysis of 56 preoperative cases from the AOSpine North America Myelopathy study.

    PubMed

    Smith, Justin S; Lafage, Virginie; Ryan, Devon J; Shaffrey, Christopher I; Schwab, Frank J; Patel, Alpesh A; Brodke, Darrel S; Arnold, Paul M; Riew, K Daniel; Traynelis, Vincent C; Radcliff, Kris; Vaccaro, Alexander R; Fehlings, Michael G; Ames, Christopher P

    2013-10-15

    Post hoc analysis of prospectively collected data. Development of methods to determine in vivo spinal cord dimensions and application to correlate preoperative alignment, myelopathy, and health-related quality-of-life scores in patients with cervical spondylotic myelopathy (CSM). CSM is the leading cause of spinal cord dysfunction. The association between cervical alignment, sagittal balance, and myelopathy has not been well characterized. This was a post hoc analysis of the prospective, multicenter AOSpine North America CSM study. Inclusion criteria for this study required preoperative cervical magnetic resonance imaging (MRI) and neutral sagittal cervical radiography. Techniques for MRI assessment of spinal cord dimensions were developed. Correlations between imaging and health-related quality-of-life scores were assessed. Fifty-six patients met inclusion criteria (mean age = 55.4 yr). The modified Japanese Orthopedic Association (mJOA) scores correlated with C2-C7 sagittal vertical axis (SVA) (r = -0.282, P = 0.035). Spinal cord volume correlated with cord length (r = 0.472, P < 0.001) and cord average cross-sectional area (r = 0.957, P < 0.001). For all patients, no correlations were found between MRI measurements of spinal cord length, volume, mean cross-sectional area or surface area, and outcomes. For patients with cervical lordosis, mJOA scores correlated positively with cord volume (r = 0.366, P = 0.022), external cord area (r = 0.399, P = 0.012), and mean cross-sectional cord area (r = 0.345, P = 0.031). In contrast, for patients with cervical kyphosis, mJOA scores correlated negatively with cord volume (r = -0.496, P = 0.043) and mean cross-sectional cord area (r = -0.535, P = 0.027). This study is the first to correlate cervical sagittal balance (C2-C7 SVA) to myelopathy severity. We found a moderate negative correlation in kyphotic patients of cord volume and cross-sectional area to mJOA scores. The opposite (positive correlation) was found for

  7. 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.

  8. JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain

    PubMed Central

    Gao, Yong-Jing; Zhang, Ling; Samad, Omar Abdel; Suter, Marc R.; Yasuhiko, Kawasaki; Xu, Zhen-Zhong; Park, Jong-Yeon; Lind, Anne-Li; Ma, Qiufu; Ji, Ru-Rong

    2009-01-01

    Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, TNF-α transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-α/JNK pathway. MCP-1 upregulation by TNF-α was dose-dependently inhibited by the JNK inhibitors SP600125 and D-JNKI-1. Spinal injection of TNF-α produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Further, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase (ERK) in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous excitatory synaptic currents (sEPSCs) but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Taken together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes following JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management. PMID:19339605

  9. JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain.

    PubMed

    Gao, Yong-Jing; Zhang, Ling; Samad, Omar Abdel; Suter, Marc R; Yasuhiko, Kawasaki; Xu, Zhen-Zhong; Park, Jong-Yeon; Lind, Anne-Li; Ma, Qiufu; Ji, Ru-Rong

    2009-04-01

    Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, tumor necrosis factor alpha (TNF-alpha) transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-alpha/JNK pathway. MCP-1 upregulation by TNF-alpha was dose dependently inhibited by the JNK inhibitors SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) and D-JNKI-1. Spinal injection of TNF-alpha produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Furthermore, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch-clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous EPSCs but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes after JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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

  15. Single fraction spine radiosurgery for myeloma epidural spinal cord compression.

    PubMed

    Jin, Ryan; Rock, Jack; Jin, Jian-Yue; Janakiraman, Nalini; Kim, Jae Ho; Movsas, Benjamin; Ryu, Samuel

    2009-01-01

    Radiosurgery delivers highly focused radiation beams to the defined target with high precision and accuracy. It has been demonstrated that spine radiosurgery can be safely used for treatment of spine metastasis with rapid and durable pain control, but without detrimental effects to the spinal cord. This study was carried out to determine the role of single fraction radiosurgery for epidural spinal cord compression due to multiple myeloma. A total of 31 lesions in 24 patients with multiple myeloma, who presented with epidural spinal cord compression, were treated with spine radiosurgery. Single fraction radiation dose of 10-18 Gy (median of 16 Gy) was administered to the involved spine including the epidural or paraspinal tumor. Patients were followed up with clinical exams and imaging studies. Median follow-up was 11.2 months (range 1-55). Primary endpoints of this study were pain control, neurological improvement, and radiographic tumor control. Overall pain control rate was 86%; complete relief in 54%, and partial relief in 32% of the patients. Seven patients presented with neurological deficits. Five patients neurologically improved or became normal after radiosurgery. Complete radiographic response of the epidural tumor was noted in 81% at 3 months after radiosurgery. During the follow-up time, there was no radiographic or neurological progression at the treated spine. The treatment was non-invasive and well tolerated. Single fraction radiosurgery achieved an excellent clinical and radiographic response of myeloma epidural spinal cord compression. Radiosurgery can be a viable treatment option for myeloma epidural compression.

  16. 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.

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

    PubMed Central

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

    2014-01-01

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

  18. 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.

  19. Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury.

    PubMed

    Fairbanks, C A; Schreiber, K L; Brewer, K L; Yu, C G; Stone, L S; Kitto, K F; Nguyen, H O; Grocholski, B M; Shoeman, D W; Kehl, L J; Regunathan, S; Reis, D J; Yezierski, R P; Wilcox, G L

    2000-09-12

    Antagonists of glutamate receptors of the N-methyl-d-aspartate subclass (NMDAR) or inhibitors of nitric oxide synthase (NOS) prevent nervous system plasticity. Inflammatory and neuropathic pain rely on plasticity, presenting a clinical opportunity for the use of NMDAR antagonists and NOS inhibitors in chronic pain. Agmatine (AG), an endogenous neuromodulator present in brain and spinal cord, has both NMDAR antagonist and NOS inhibitor activities. We report here that AG, exogenously administered to rodents, decreased hyperalgesia accompanying inflammation, normalized the mechanical hypersensitivity (allodynia/hyperalgesia) produced by chemical or mechanical nerve injury, and reduced autotomy-like behavior and lesion size after excitotoxic spinal cord injury. AG produced these effects in the absence of antinociceptive effects in acute pain tests. Endogenous AG also was detected in rodent lumbosacral spinal cord in concentrations similar to those previously detected in brain. The evidence suggests a unique antiplasticity and neuroprotective role for AG in processes underlying persistent pain and neuronal injury.

  20. Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury

    PubMed Central

    Fairbanks, Carolyn A.; Schreiber, Kristin L.; Brewer, Kori L.; Yu, Chen-Guang; Stone, Laura S.; Kitto, Kelley F.; Nguyen, H. Oanh; Grocholski, Brent M.; Shoeman, Don W.; Kehl, Lois J.; Regunathan, Soundararajan; Reis, Donald J.; Yezierski, Robert P.; Wilcox, George L.

    2000-01-01

    Antagonists of glutamate receptors of the N-methyl-d-aspartate subclass (NMDAR) or inhibitors of nitric oxide synthase (NOS) prevent nervous system plasticity. Inflammatory and neuropathic pain rely on plasticity, presenting a clinical opportunity for the use of NMDAR antagonists and NOS inhibitors in chronic pain. Agmatine (AG), an endogenous neuromodulator present in brain and spinal cord, has both NMDAR antagonist and NOS inhibitor activities. We report here that AG, exogenously administered to rodents, decreased hyperalgesia accompanying inflammation, normalized the mechanical hypersensitivity (allodynia/hyperalgesia) produced by chemical or mechanical nerve injury, and reduced autotomy-like behavior and lesion size after excitotoxic spinal cord injury. AG produced these effects in the absence of antinociceptive effects in acute pain tests. Endogenous AG also was detected in rodent lumbosacral spinal cord in concentrations similar to those previously detected in brain. The evidence suggests a unique antiplasticity and neuroprotective role for AG in processes underlying persistent pain and neuronal injury. PMID:10984543

  1. 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.

  2. Involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters in neonatal rat spinal cord.

    PubMed Central

    Suzuki, H; Yoshioka, K; Yanagisawa, M; Urayama, O; Kurihara, T; Hosoki, R; Saito, K; Otsuka, M

    1994-01-01

    1. The possible involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters was examined in the spinal cord of the neonatal rat. 2. The magnitude of substance P (SP)- or neurokinin A (NKA)-evoked depolarization of a lumbar ventral root in the isolated spinal cord preparation was increased by a mixture of peptidase inhibitors, consisting of actinonin (6 microM), arphamenine B (6 microM), bestatin (10 microM), captopril (10 microM) and thiorphan (0.3 microM). The mixture augmented the response to NKA more markedly than that to SP. 3. In the isolated spinal cord-cutaneous nerve preparation, the saphenous nerve-evoked slow depolarization of the L3 ventral root was augmented by the mixture of peptidase inhibitors in the presence of naloxone (0.5 microM) but not in the presence of both naloxone and a tachykinin receptor antagonist, GR71251 (5 microM). 4. Application of capsaicin (0.5 microM) for 6 min to the spinal cord evoked an increase in the release of SP from the spinal cord. The amount of SP released was significantly augmented by the mixture of peptidase inhibitors. 5. Synaptic membrane fractions were prepared from neonatal rat spinal cords. These fractions showed degrading activities for SP and NKA and the activities were inhibited by the mixture of peptidase inhibitors. The degrading activity for NKA was higher than that for SP and the inhibitory effect of the mixture for NKA was more marked than that for SP. Although some other fractions obtained from homogenates of spinal cords showed higher degrading activities for SP, these activities were insensitive to the mixture of peptidase inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7529113

  3. Stem cell clinical trials for spinal cord injury: readiness, reluctance, redefinition.

    PubMed

    Illes, J; Reimer, J C; Kwon, B K

    2011-11-01

    A wealth of scientific and clinical research has focused on the use of stem cells as a potential therapy for spinal cord injury (SCI), culminating most recently in the initiation of clinical trials. However, with the urgency that scientists and clinicians have undertaken to move forward with novel therapies for this devastating injury, the perspectives of stakeholders who live with a SCI have been left behind. Translational research in this rapidly growing field therefore overlooks a critically important viewpoint. We address this concern with a qualitative study of the perspectives on experimental stem cell treatments from individuals who have actually suffered a spinal cord injury. Using focus groups and interviews, we engaged individuals with thoracic and cervical SCIs at sub-acute and chronic stages post-injury. We found four major themes that inform the progression of stem cell research to clinical trials: 'readiness', 'the here and now', 'wait and see', and 'informed hope'. Taken together, the data suggest a profound difference related to target timing of stem cell clinical trials and the perspectives about timing from those who are the end-beneficiaries of therapy. To bridge this gap, we conclude with a number of considerations for the timing disparity of trials and recommendations for improving informed consent.

  4. 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

  5. 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.

  6. Spinal cord compression in a patient with a pain pump for failed back syndrome: a chalk-like precipitate mimicking a spinal cord neoplasm: case report.

    PubMed

    Wadhwa, Rishi K; Shaya, Mark R; Nanda, Anil

    2006-02-01

    The use of intrathecal morphine has been effective with few complications for chronic intractable pain of both benign and malignant origins. A rare but serious problem that exists is the formation of an inflammatory mass at the catheter tip of the pain pump. We report the case of a 67-year-old female patient with failed back syndrome who presented with sensory complaints and back pain. Magnetic resonance imaging revealed impingement on the thoracic cord by a mass. The mass was originally thought to be a spinal cord tumor; however, operation and chemical analysis of the mass showed that it was a bupivacaine precipitate at the tip of the catheter of the pain pump. This is the first such case, to our knowledge, of a bupivacaine precipitate mimicking a spinal cord tumor.

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

    PubMed Central

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

    2014-01-01

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

  8. (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.

  9. 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.

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

    NASA Technical Reports Server (NTRS)

    Cardus, David

    1999-01-01

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

  11. Factors predicting publication of spinal cord injury trials registered on www.ClinicalTrials. gov.

    PubMed

    DePasse, J Mason; Park, Sara; Eltorai, Adam E M; Daniels, Alan H

    2018-02-06

    Treatment options for spinal cord injuries are currently limited, but multiple clinical trials are underway for a variety of interventions, drugs, and devices. The Food and Drug Administration website www.ClinicalTrials.gov catalogues these trials and includes information on the status of the trial, date of initiation and completion, source of funding, and region. This investigation assesses the factors associated with publication and the publication rate of spinal cord injury trials. Retrospective analysis of publically available data on www.ClinicalTrials.gov. The www.ClinicalTrials.gov was queried for all trials on patients with spinal cord injury, and these trials were assessed for status, type of intervention, source of funding, and region. Multiple literature searches were performed on all completed trials to determine publication status. There were 626 studies identified concerning the treatment of patients with spinal cord injury, of which 250 (39.9%) were completed. Of these, only 119 (47.6%) were published. There was no significant difference in the rate of publication between regions (p> 0.16) or by study type (p> 0.29). However, trials that were funded by the NIH were more likely to be published than trials funded by industry (p= 0.01). The current publication rate of spinal cord injury trials is only 47.6%, though this rate is similar to the publication rate for trials in other fields. NIH-funded trials are significantly more likely to become published than industry-funded trials, which could indicate that some trials remain unpublished due to undesirable results. However, it is also likely that many trials on spinal cord injury yield negative results, as treatments are often ineffective.

  12. Spinal cord testing: auditing for quality assurance.

    PubMed

    Marr, J A; Reid, B

    1991-04-01

    A quality assurance audit of spinal cord testing as documented by staff nurses was carried out. Twenty-five patient records were examined for accuracy of documented testing and compared to assessments performed by three investigators. A pilot study established interrater reliability of a tool that was designed especially for this study. Results indicated staff nurses failed to meet pre-established 100% standard in all categories of testing when compared with investigator's findings. Possible reasons for this disparity are discussed as well as indications for modifications in the spinal testing record, teaching program and preset standards.

  13. Employment among Spinal Cord Injured Patients Living in Turkey: A Cross-Sectional Study

    ERIC Educational Resources Information Center

    Gunduz, Berrin; Erhan, Belgin; Bardak, Ayse Nur

    2010-01-01

    The aim of this study was to determine the rate of employment and to establish the factors affecting vocational status in spinal cord injured patients living in Turkey. One hundred and fifty-two traumatic spinal cord injured patients older than 18 years with injury duration of at least 1 year and living in the community were included in the study;…

  14. Inflammatory myofibroblastic tumour of the spinal cord: case report and review of the literature.

    PubMed

    Despeyroux-Ewers, M; Catalaâ, I; Collin, L; Cognard, C; Loubes-Lacroix, F; Manelfe, C

    2003-11-01

    Inflammatory myofibroblastic tumours (IMT), also called inflammatory pseudotumours, nodular lymphoid hyperplasia, plasma-cell granuloma and fibrous xanthoma, are rare soft-tissue lesions characterised by inflammatory cells and a fibrous stroma. Clinically and radiologically, they may look like malignant tumours. They rarely affect the central nervous system and are very rare in the spinal cord. We report an IMT of the spinal cord in a 22-year-old woman presenting with spinal cord compression and a cauda equina syndrome. MRI showed a lesion at T9 with extramedullary and intramedullary components giving low signal on T2-weighted images and enhancing homogeneously. Pial lesions on the lumbar enlargement and thoracic spinal were present 11 months after surgery, when the lesion recurred. We present the radiological, operative and pathological findings and review the literature.

  15. Hair Follicle-Associated Pluripotent (HAP) Stem Cells in Gelfoam® Histoculture for Use in Spinal Cord Repair.

    PubMed

    Liu, Fang; Hoffman, Robert M

    2018-01-01

    The stem cell marker, nestin, is expressed in the hair follicle, both in cells in the bulge area (BA) and the dermal papilla (DP). Nestin-expressing hair follicle-associated-pluripotent (HAP) stem cells of both the BA and DP have been previously shown to be able to form neurons, heart muscle cells, and other non-follicle cell types. The ability of the nestin-expressing HAP stem cells from the BA and DP to repair spinal cord injury was compared. Nestin-expressing HAP stem cells from both the BA and DP grew very well on Gelfoam ® . The HAP stem cells attached to the Gelfoam ® within 1 h. They grew along the grids of the Gelfoam ® during the first 2 or 3 days. Later they spread into the Gelfoam ® . After transplantation of Gelfoam ® cultures of nestin-expressing BA or DP HAP stem cells into the injured spinal cord (including the Gelfoam ® ) nestin-expressing BA and DP cells were observed to be viable over 100 days post-surgery. Hematoxylin and eosin (H&E) staining showed connections between the transplanted cells and the host spine tissue. Immunohistochemistry showed many Tuj1-, Isl 1/2, and EN1-positive cells and nerve fibers in the transplanted area of the spinal cord after BA Gelfoam ® or DP Gelfoam ® cultures were transplanted to the spine. The spinal cord of mice was injured to effect hind-limb paralysis. Twenty-eight days after transplantation with BA or DP HAP stem cells on Gelfoam ® to the injured area of the spine, the mice recovered normal locomotion.

  16. Spasticity therapy reacts to astrocyte GluA1 receptor upregulation following spinal cord injury

    PubMed Central

    Gómez-Soriano, Julio; Goiriena, Eider; Taylor, Julian

    2010-01-01

    For almost three decades intrathecal baclofen therapy has been the standard treatment for spinal cord injury spasticity when oral medication is ineffective or produces serious side effects. Although intrathecal baclofen therapy has a good clinical benefit-risk ratio for spinal spasticity, tolerance and the life-threatening withdrawal syndrome present serious problems for its management. Now, in an experimental model of spinal cord injury spasticity, AMPA receptor blockade with NGX424 (Tezampanel) has been shown to reduce stretch reflex activity alone and during tolerance to intrathecal baclofen therapy. These results stem from the observation that GluA1 receptors are overexpressed on reactive astrocytes following experimental ischaemic spinal cord injury. Although further validation is required, the appropriate choice of AMPA receptor antagonists for treatment of stretch hyperreflexia based on our recent understanding of reactive astrocyte neurobiology following spinal cord injury may lead to the development of a better adjunct clinical therapy for spasticity without the side effects of intrathecal baclofen therapy. LINKED ARTICLE This article is a commentary on Oshiro et al., pp. 976–985 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2010.00954.x PMID:20662840

  17. Spinal cord stimulation for treatment of meralgia paresthetica.

    PubMed

    Barna, Steven A; Hu, M Melvin; Buxo, Carlos; Trella, Jason; Cosgrove, G Rees

    2005-07-01

    Meralgia paresthetica is a clinical syndrome of pain, dysesthesia or both, in the anterolateral thigh. It is associated with an entrapment mononeuropathy of the lateral femoral cutaneous nerve. Diagnosis of meralgia paresthetica is typically made clinically and is based on the characteristic location of pain or dysesthesia, sensory abnormality on exam, and absence of any other neurological abnormality in the leg. The majority of patients with meralgia paresthetica respond well to conservative treatment. To present a case of intractable meralgia paresthetica in which conservative treatment options failed but which was successfully treated with a spinal cord stimulator. A 44-year-old woman presented to the pain clinic with a one-year history of bilateral anterolateral thigh pain. History, physical exam, and diagnostic work-up were consistent with meralgia paresthetica. Multiple medications, physical therapy, and chiropractic therapy were not successful for this patient. In addition, local anesthetic/steroid injection of the lateral femoral cutaneous nerve provided only short-term relief. Ultimately, a spinal cord stimulator was implanted after a successful temporary percutaneous trial. Two months after the implantation, she continued to have 100% pain relief, worked full-time, was physically active, and no longer required any pain medication including opioids. An implanted spinal cord stimulator may be an ideal treatment for intractable meralgia paresthetica after conservative treatments have failed because it is not destructive and can always be explanted without significant permanent adverse effects.

  18. Understanding and Preventing Loss to Follow-up: Experiences From the Spinal Cord Injury Model Systems.

    PubMed

    Kim, Hwasoon; Cutter, Gary R; George, Brandon; Chen, Yuying

    2018-01-01

    Background: One of the most critical threats to the validity of any longitudinal research is the bias caused by study attrition. Prevention efforts should be focused on those individuals at high risk of non-participation to improve the generalizability of study findings. Objective: To identify demographic and clinical factors associated with loss to follow-up (FU) at post-injury years 1 to 35 among 25,871 people with spinal cord injury (SCI) enrolled in the National Spinal Cord Injury Database. Methods: Loss to FU was defined as no research information obtained from participants who were eligible for the planned data collection. Generalized linear mixed models were used for analysis of factors at each post-injury year. Results: The loss to FU rates were 23.1% and 32.9% for post-injury years 1 and 5, respectively, and remained >40% between post-injury years 20 and 35. The FU rate varied by study sites and was improved in recent injury cohorts. People who were more seriously injured and those who attained higher levels of education were more likely to return for FU than their counterparts. People who were at risk of being marginalized in society (non-whites, those with less education, the unemployed, victims of violence, and those with no health insurance) had the highest odds of being lost to FU across all post-injury years. Conclusion: These findings can be used to identify individuals who are less likely to participate in follow-up, which may allow targeted attention to improve their response rate.

  19. 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

  20. Combining Constitutively Active Rheb Expression and Chondroitinase Promotes Functional Axonal Regeneration after Cervical Spinal Cord Injury.

    PubMed

    Wu, Di; Klaw, Michelle C; Connors, Theresa; Kholodilov, Nikolai; Burke, Robert E; Côté, Marie-Pascale; Tom, Veronica J

    2017-12-06

    After spinal cord injury (SCI), severed axons in the adult mammalian CNS are unable to mount a robust regenerative response. In addition, the glial scar at the lesion site further restricts the regenerative potential of axons. We hypothesized that a combinatorial approach coincidentally targeting these obstacles would promote axonal regeneration. We combined (1) transplantation of a growth-permissive peripheral nerve graft (PNG) into an incomplete, cervical lesion cavity; (2) transduction of neurons rostral to the SCI site to express constitutively active Rheb (caRheb; a Ras homolog enriched in brain), a GTPase that directly activates the growth-promoting pathway mammalian target of rapamycin (mTOR) via AAV-caRheb injection; and (3) digestion of growth-inhibitory chondroitin sulfate proteoglycans within the glial scar at the distal PNG interface using the bacterial enzyme chondroitinase ABC (ChABC). We found that expressing caRheb in neurons post-SCI results in modestly yet significantly more axons regenerating across a ChABC-treated distal graft interface into caudal spinal cord than either treatment alone. Excitingly, we found that caRheb+ChABC treatment significantly potentiates the formation of synapses in the host spinal cord and improves the animals' ability to use the affected forelimb. Thus, this combination strategy enhances functional axonal regeneration following a cervical SCI. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  1. Involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters in neonatal rat spinal cord.

    PubMed

    Suzuki, H; Yoshioka, K; Yanagisawa, M; Urayama, O; Kurihara, T; Hosoki, R; Saito, K; Otsuka, M

    1994-09-01

    1. The possible involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters was examined in the spinal cord of the neonatal rat. 2. The magnitude of substance P (SP)- or neurokinin A (NKA)-evoked depolarization of a lumbar ventral root in the isolated spinal cord preparation was increased by a mixture of peptidase inhibitors, consisting of actinonin (6 microM), arphamenine B (6 microM), bestatin (10 microM), captopril (10 microM) and thiorphan (0.3 microM). The mixture augmented the response to NKA more markedly than that to SP. 3. In the isolated spinal cord-cutaneous nerve preparation, the saphenous nerve-evoked slow depolarization of the L3 ventral root was augmented by the mixture of peptidase inhibitors in the presence of naloxone (0.5 microM) but not in the presence of both naloxone and a tachykinin receptor antagonist, GR71251 (5 microM). 4. Application of capsaicin (0.5 microM) for 6 min to the spinal cord evoked an increase in the release of SP from the spinal cord. The amount of SP released was significantly augmented by the mixture of peptidase inhibitors. 5. Synaptic membrane fractions were prepared from neonatal rat spinal cords. These fractions showed degrading activities for SP and NKA and the activities were inhibited by the mixture of peptidase inhibitors. The degrading activity for NKA was higher than that for SP and the inhibitory effect of the mixture for NKA was more marked than that for SP. Although some other fractions obtained from homogenates of spinal cords showed higher degrading activities for SP, these activities were insensitive to the mixture of peptidase inhibitors. 6. Effects of individual peptidase inhibitors on the enzymatic degradation of SP and NKA by synaptic membrane fractions were examined. Thiorphan, actinonin and captopril inhibited SP degradation, while thiorphan and actinonin, but not captopril, inhibited NKA degradation. The potency of the inhibition of each peptidase inhibitor was lower than

  2. [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

  3. New products tissue-engineering in the treatment of spinal cord injury

    NASA Astrophysics Data System (ADS)

    Bolshakov, I. N.; Sergienko, V. I.; Kiselev, S. L.; Lagarkova, M. A.; Remigaylo, A. A.; Mihaylov, A. A.; Prokopenko, S. V.

    2015-11-01

    In the treatment of patients with complicated spinal cord injury the Russian Health spends about one million rubles for each patient in the acute and the interim period after the injury. The number of complicated spinal cord injury is different in geographical areas Russian Federation from 30 to 50 people per 1 million that is affected by the year 5600. Applied to the present surgical and pharmacological techniques provide unsatisfactory results or minimally effective treatment. Transplantation of 100 thousand neuronal mouse predecessors (24 rats) or human neuronal predecessors (18 rats) in the anatomical gap rat spinal cord, followed by analysis of neurological deficit. The neuro-matrix implantation in the rat spinal cord containing 100 thousand neuronal precursors hESC, repeatable control neuro-matrix transplantation, non-cell mass, eliminating neurological deficit for 14 weeks after transplantation about 5-9 points on the scale of the BBB. The cultivation under conditions in vitro human induced pluripotent stem cells on collagen-chitosan matrix (hIPSC) showed that neurons differentiated from induced pluripotent stem cells grown on scaffolds as compact groups and has no neurites. Cells do not penetrate into the matrix during long-term cultivation and formed near the surface of the spherical structures resembling neurospheres. At least 90% of the cells were positive for the neuronal marker tubulin b3. Further studies should be performed to examine the compatibility of neuronal cultures and matrices.

  4. 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.

  5. Brachial plexus injury mimicking a spinal-cord injury

    PubMed Central

    Macyszyn, Luke J.; Gonzalez-Giraldo, Ernesto; Aversano, Michael; Heuer, Gregory G.; Zager, Eric L.; Schuster, James M.

    2010-01-01

    Objective: High-energy impact to the head, neck, and shoulder can result in cervical spine as well as brachial plexus injuries. Because cervical spine injuries are more common, this tends to be the initial focus for management. We present a case in which the initial magnetic resonance imaging (MRI) was somewhat misleading and a detailed neurological exam lead to the correct diagnosis. Clinical presentation: A 19-year-old man presented to the hospital following a shoulder injury during football practice. The patient immediately complained of significant pain in his neck, shoulder, and right arm and the inability to move his right arm. He was stabilized in the field for a presumed cervical-spine injury and transported to the emergency department. Intervention: Initial radiographic assessment (C-spine CT, right shoulder x-ray) showed no bony abnormality. MRI of the cervical-spine showed T2 signal change and cord swelling thought to be consistent with a cord contusion. With adequate pain control, a detailed neurological examination was possible and was consistent with an upper brachial plexus avulsion injury that was confirmed by CT myelogram. The patient failed to make significant neurological recovery and he underwent spinal accessory nerve grafting to the suprascapular nerve to restore shoulder abduction and external rotation, while the phrenic nerve was grafted to the musculocutaneous nerve to restore elbow flexion. Conclusion: Cervical spinal-cord injuries and brachial plexus injuries can occur by the same high energy mechanisms and can occur simultaneously. As in this case, MRI findings can be misleading and a detailed physical examination is the key to diagnosis. However, this can be difficult in polytrauma patients with upper extremity injuries, head injuries or concomitant spinal-cord injury. Finally, prompt diagnosis and early surgical renerveration have been associated with better long-term recovery with certain types of injury. PMID:22956928

  6. 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.

  7. 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.

  8. 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)

  9. 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.

  10. 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

  11. Conditional Sox9 ablation improves locomotor recovery after spinal cord injury by increasing reactive sprouting.

    PubMed

    McKillop, William M; York, Elisa M; Rubinger, Luc; Liu, Tony; Ossowski, Natalie M; Xu, Kathy; Hryciw, Todd; Brown, Arthur

    2016-09-01

    The absence of axonal regeneration after spinal cord injury (SCI) has been attributed to the up-regulation of axon-repelling molecules, such as chondroitin sulfate proteoglycans (CSPGs) present in the glial scar that forms post-SCI. We previously identified the transcription factor SOX9 as a key up-regulator of CSPG production and also demonstrated that conditional Sox9 ablation leads to decreased CSPG levels and improved recovery of hind limb function after SCI. We herein demonstrate increased neural input onto spinal neurons caudal to the lesion in spinal cord injured Sox9 conditional knock out mice as indicated by increased levels of the presynaptic markers synaptophysin and vesicular glutamate transporter 1 (VGLUT1) compared to controls. Axonal sparing, long-range axonal regeneration and reactive sprouting were investigated as possible explanations for the increase in neural inputs caudal to the lesion and for the improved locomotor outcomes in spinal cord-injured Sox9 conditional knock out mice. Whereas retrograde tract-tracing studies failed to reveal any evidence for increased axonal sparing or for long-range regeneration in the Sox9 conditional knock out mice, anterograde tract-tracing experiments demonstrated increased reactive sprouting caudal to the lesion after SCI. Finally we demonstrate that application of a broad spectrum MMP inhibitor to reduce CSPG degradation in Sox9 conditional knock out mice prevents the improvements in locomotor recovery observed in untreated Sox9 conditional knock out mice. These results suggest that improved recovery of locomotor function in Sox9 conditional knock out mice after SCI is due to increased reactive sprouting secondary to reduced CSPG levels distal to the lesion. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Alpha-2 agonist attenuates ischemic injury in spinal cord neurons.

    PubMed

    Freeman, Kirsten A; Puskas, Ferenc; Bell, Marshall T; Mares, Joshua M; Foley, Lisa S; Weyant, Michael J; Cleveland, Joseph C; Fullerton, David A; Meng, Xianzhong; Herson, Paco S; Reece, T Brett

    2015-05-01

    Paraplegia secondary to spinal cord ischemia-reperfusion injury remains a devastating complication of thoracoabdominal aortic intervention. The complex interactions between injured neurons and activated leukocytes have limited the understanding of neuron-specific injury. We hypothesize that spinal cord neuron cell cultures subjected to oxygen-glucose deprivation (OGD) would simulate ischemia-reperfusion injury, which could be attenuated by specific alpha-2a agonism in an Akt-dependent fashion. Spinal cords from perinatal mice were harvested, and neurons cultured in vitro for 7-10 d. Cells were pretreated with 1 μM dexmedetomidine (Dex) and subjected to OGD in an anoxic chamber. Viability was determined by MTT assay. Deoxyuridine-triphosphate nick-end labeling staining and lactate dehydrogenase (LDH) assay were used for apoptosis and necrosis identification, respectively. Western blot was used for protein analysis. Vehicle control cells were only 59% viable after 1 h of OGD. Pretreatment with Dex significantly preserves neuronal viability with 88% viable (P < 0.05). Dex significantly decreased apoptotic cells compared with that of vehicle control cells by 50% (P < 0.05). Necrosis was not significantly different between treatment groups. Mechanistically, Dex treatment significantly increased phosphorylated Akt (P < 0.05), but protective effects of Dex were eliminated by an alpha-2a antagonist or Akt inhibitor (P < 0.05). Using a novel spinal cord neuron cell culture, OGD mimics neuronal metabolic derangement responsible for paraplegia after aortic surgery. Dex preserves neuronal viability and decreases apoptosis in an Akt-dependent fashion. Dex demonstrates clinical promise for reducing the risk of paraplegia after high-risk aortic surgery. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. The international spinal cord injury pain basic data set.

    PubMed

    Widerström-Noga, E; Biering-Sørensen, F; Bryce, T; Cardenas, D D; Finnerup, N B; Jensen, M P; Richards, J S; Siddall, P J

    2008-12-01

    To develop a basic pain data set (International Spinal Cord Injury Basic Pain Data Set, ISCIPDS:B) within the framework of the International spinal cord injury (SCI) data sets that would facilitate consistent collection and reporting of pain in the SCI population. International. The ISCIPDS:B was developed by a working group consisting of individuals with published evidence of expertise in SCI-related pain regarding taxonomy, psychophysics, psychology, epidemiology and assessment, and one representative of the Executive Committee of the International SCI Standards and Data Sets. The members were appointed by four major organizations with an interest in SCI-related pain (International Spinal Cord Society, ISCoS; American Spinal Injury Association, ASIA; American Pain Society, APS and International Association for the Study of Pain, IASP). The initial ISCIPDS:B was revised based on suggestions from members of the Executive Committee of the International SCI Standards and Data Sets, the ISCoS Scientific Committee, ASIA and APS Boards, and the Neuropathic Pain Special Interest Group of the IASP, individual reviewers and societies and the ISCoS Council. The final ISCIPDS:B contains core questions about clinically relevant information concerning SCI-related pain that can be collected by health-care professionals with expertise in SCI in various clinical settings. The questions concern pain severity, physical and emotional function and include a pain-intensity rating, a pain classification and questions related to the temporal pattern of pain for each specific pain problem. The impact of pain on physical, social and emotional function, and sleep is evaluated for each pain.

  14. Substance P stimulates proliferation of spinal neural stem cells in spinal cord injury via the mitogen-activated protein kinase signaling pathway.

    PubMed

    Kim, Kyoung-Tae; Kim, Hye-Jeong; Cho, Dae-Chul; Bae, Jae-Sung; Park, Seung-Won

    2015-09-01

    Substance P (SP) is a neuropeptide that can influence neural stem/progenitor cell (NSPC) proliferation and neurogenesis in the brain. However, we could not find any experimental study that investigates SP action in the spinal cord. The aims of our study were to investigate the potential of the neuropeptide SP in promoting the proliferation of spinal cord-derived NSPCs (SC-NSPCs) after spinal cord injury (SCI) and to clarify the roles of the mitogen-activated protein (MAP) kinase signaling pathway in the process. This is a randomized animal study. The SC-NSPCs were suspended in 100 μL of a neurobasal medium containing SP (binds neurokinin-1 receptor [NK1R]) or L-703,606 (NK1R antagonist) and cultured in a 96-well plate for 5 days. A cell proliferation assay was performed using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. A cord clipping method was used for the SCI model. Substance P and the NK1R antagonist (L-703,606) were infused intrathecally in SCI and sham models. Neural stem/progenitor cell proliferation was evaluated with immunostaining for bromodeoxyuridine (BrdU) and the immature neural marker nestin. An immunoblotting method was used for evaluating the MAP kinase signaling protein that contains extracellular signal-regulated kinases (ERKs and p38) and β-actin as the control group. In vitro, SP (0.01-10 μmol/L) increased the proliferation of cultured SC-NSPCs, with a peak increase of 35±2% at the 0.1 μmol/L concentration. Substance P of 0.1 μmol/L continuously increased SC-NSPC proliferation from 6 hours to 5 days, whereas the proliferation decreased from 18% to 98% with L-703,606 (1-10 μM). Intrathecal infusion of SP (1 μmol/L) for 7 days significantly increased the number of proliferating NPSCs (cells positive for both BrdU and nestin) in the spinal cord (by 120±17%, p<.05) in adult rats, but infusion of L-703,606 (10 μmol/L) significantly decreased the post-SCI induction of NPSC proliferation

  15. Plasticity of spinal centers in spinal cord injury patients: new concepts for gait evaluation and training.

    PubMed

    Scivoletto, Giorgio; Ivanenko, Yuri; Morganti, Barbara; Grasso, Renato; Zago, Mirka; Lacquaniti, Francesco; Ditunno, John; Molinari, Marco

    2007-01-01

    Recent data on spinal cord plasticity after spinal cord injury (SCI) were reviewed to analyze the influence of training on the neurophysiological organization of locomotor spinal circuits in SCI patients. In particular, the authors studied the relationship between central pattern generators (CPGs) and motor neuron pool activation during gait. An analysis of the relations between locomotor recovery and compensatory mechanisms focuses on the hierarchical organization of gait parameters and allows characterizing kinematic parameters that are highly stable during different gait conditions and in recovered gait after SCI. The importance of training characteristics and the use of robotic/automated devices in gait recovery is analyzed and discussed. The role of CPG in defining kinematic gait parameters is summarized, and spatio-temporal maps of EMG activity during gait are used to clarify the role of CPG plasticity in sustaining gait recovery.

  16. Transplantation of neurotrophin-3-transfected bone marrow mesenchymal stem cells for the repair of spinal cord injury.

    PubMed

    Dong, Yuzhen; Yang, Libin; Yang, Lin; Zhao, Hongxing; Zhang, Chao; Wu, Dapeng

    2014-08-15

    Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesenchymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal cord injury. These results indicate that neurotrophin-3 can promote the survival of bone marrow mesenchymal stem cells transplanted into the region of spinal cord injury and potentially enhance the therapeutic effect in the repair of spinal cord injury.

  17. 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

  18. A First-in-Human, Phase I Study of Neural Stem Cell Transplantation for Chronic Spinal Cord Injury.

    PubMed

    Curtis, Erik; Martin, Joel R; Gabel, Brandon; Sidhu, Nikki; Rzesiewicz, Teresa K; Mandeville, Ross; Van Gorp, Sebastiaan; Leerink, Marjolein; Tadokoro, Takahiro; Marsala, Silvia; Jamieson, Catriona; Marsala, Martin; Ciacci, Joseph D

    2018-06-01

    We tested the feasibility and safety of human-spinal-cord-derived neural stem cell (NSI-566) transplantation for the treatment of chronic spinal cord injury (SCI). In this clinical trial, four subjects with T2-T12 SCI received treatment consisting of removal of spinal instrumentation, laminectomy, and durotomy, followed by six midline bilateral stereotactic injections of NSI-566 cells. All subjects tolerated the procedure well and there have been no serious adverse events to date (18-27 months post-grafting). In two subjects, one to two levels of neurological improvement were detected using ISNCSCI motor and sensory scores. Our results support the safety of NSI-566 transplantation into the SCI site and early signs of potential efficacy in three of the subjects warrant further exploration of NSI-566 cells in dose escalation studies. Despite these encouraging secondary data, we emphasize that this safety trial lacks statistical power or a control group needed to evaluate functional changes resulting from cell grafting. Copyright © 2018. Published by Elsevier Inc.

  19. 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.

  20. Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury

    PubMed Central

    Wenger, Nikolaus; Moraud, Eduardo Martin; Gandar, Jerome; Musienko, Pavel; Capogrosso, Marco; Baud, Laetitia; Le Goff, Camille G.; Barraud, Quentin; Pavlova, Natalia; Dominici, Nadia; Minev, Ivan R.; Asboth, Leonie; Hirsch, Arthur; Duis, Simone; Kreider, Julie; Mortera, Andrea; Haverbeck, Oliver; Kraus, Silvio; Schmitz, Felix; DiGiovanna, Jack; van den Brand, Rubia; Bloch, Jocelyne; Detemple, Peter; Lacour, Stéphanie P.; Bézard, Erwan; Micera, Silvestro; Courtine, Grégoire

    2016-01-01

    Electrical neuromodulation of lumbar segments improves motor control after spinal cord injury in animal models and humans. However, the physiological principles underlying the effect of this intervention remain poorly understood, which has limited this therapeutic approach to continuous stimulation applied to restricted spinal cord locations. Here, we developed novel stimulation protocols that reproduce the natural dynamics of motoneuron activation during locomotion. For this, we computed the spatiotemporal activation pattern of muscle synergies during locomotion in healthy rats. Computer simulations identified optimal electrode locations to target each synergy through the recruitment of proprioceptive feedback circuits. This framework steered the design of spatially selective spinal implants and real–time control software that modulate extensor versus flexor synergies with precise temporal resolution. Spatiotemporal neuromodulation therapies improved gait quality, weight–bearing capacities, endurance and skilled locomotion in multiple rodent models of spinal cord injury. These new concepts are directly translatable to strategies to improve motor control in humans. PMID:26779815

  1. 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

  2. Changes in Body Temperature in Incomplete Spinal Cord Injury by Digital Infrared Thermographic Imaging

    PubMed Central

    Song, Yun-Gyu; Won, Yu Hui; Park, Sung-Hee; Ko, Myoung-Hwan

    2015-01-01

    Objective To investigate changes in the core temperature and body surface temperature in patients with incomplete spinal cord injuries (SCI). In incomplete SCI, the temperature change is difficult to see compared with complete spinal cord injuries. The goal of this study was to better understand thermal regulation in patients with incomplete SCI. Methods Fifty-six SCI patients were enrolled, and the control group consisted of 20 healthy persons. The spinal cord injuries were classified according to International Standards for Neurological Classification of Spinal Cord Injury. The patients were classified into two groups: upper (neurological injury level T6 or above) and lower (neurological injury level T7 or below) SCIs. Body core temperature was measured using an oral thermometer, and body surface temperature was measured using digital infrared thermographic imaging. Results Twenty-nine patients had upper spinal cord injuries, 27 patients had lower SCIs, and 20 persons served as the normal healthy persons. Comparing the skin temperatures of the three groups, the temperatures at the lower abdomen, anterior thigh and anterior tibia in the patients with upper SCIs were lower than those of the normal healthy persons and the patients with lower SCIs. No significant temperature differences were observed between the normal healthy persons and the patients with lower SCIs. Conclusion In our study, we found thermal dysregulation in patients with incomplete SCI. In particular, body surface temperature regulation was worse in upper SCIs than in lower injuries. Moreover, cord injury severity affected body surface temperature regulation in SCI patients. PMID:26605167

  3. 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.

  4. 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

  5. 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

  6. 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

  7. Autonomic Nervous System in Paralympic Athletes with Spinal Cord Injury.

    PubMed

    Walter, Matthias; Krassioukov, Andrei V

    2018-05-01

    Individuals sustaining a spinal cord injury (SCI) frequently suffer from sensorimotor and autonomic impairment. Damage to the autonomic nervous system results in cardiovascular, respiratory, bladder, bowel, and sexual dysfunctions, as well as temperature dysregulation. These complications not only impede quality of life, but also affect athletic performance of individuals with SCI. This article summarizes existing evidence on how damage to the spinal cord affects the autonomic nervous system and impacts the performance in athletes with SCI. Also discussed are frequently used performance-enhancing strategies, with a special focus on their legal aspect and implication on the athletes' health. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Cell therapy for spinal cord injury informed by electromagnetic waves.

    PubMed

    Finnegan, Jack; Ye, Hui

    2016-10-01

    Spinal cord injury devastates the CNS, besetting patients with symptoms including but not limited to: paralysis, autonomic nervous dysfunction, pain disorders and depression. Despite the identification of several molecular and genetic factors, a reliable regenerative therapy has yet to be produced for this terminal disease. Perhaps the missing piece of this puzzle will be discovered within endogenous electrotactic cellular behaviors. Neurons and stem cells both show mediated responses (growth rate, migration, differentiation) to electromagnetic waves, including direct current electric fields. This review analyzes the pathophysiology of spinal cord injury, the rationale for regenerative cell therapy and the evidence for directing cell therapy via electromagnetic waves shown by in vitro experiments.

  9. Tissue sparing, behavioral recovery, supraspinal axonal sparing/regeneration following sub-acute glial transplantation in a model of spinal cord contusion.

    PubMed

    Barbour, Helen R; Plant, Christine D; Harvey, Alan R; Plant, Giles W

    2013-09-27

    It has been shown that olfactory ensheathing glia (OEG) and Schwann cell (SCs) transplantation are beneficial as cellular treatments for spinal cord injury (SCI), especially acute and sub-acute time points. In this study, we transplanted DsRED transduced adult OEG and SCs sub-acutely (14 days) following a T10 moderate spinal cord contusion injury in the rat. Behaviour was measured by open field (BBB) and horizontal ladder walking tests to ascertain improvements in locomotor function. Fluorogold staining was injected into the distal spinal cord to determine the extent of supraspinal and propriospinal axonal sparing/regeneration at 4 months post injection time point. The purpose of this study was to investigate if OEG and SCs cells injected sub acutely (14 days after injury) could: (i) improve behavioral outcomes, (ii) induce sparing/regeneration of propriospinal and supraspinal projections, and (iii) reduce tissue loss. OEG and SCs transplanted rats showed significant increased locomotion when compared to control injury only in the open field tests (BBB). However, the ladder walk test did not show statistically significant differences between treatment and control groups. Fluorogold retrograde tracing showed a statistically significant increase in the number of supraspinal nuclei projecting into the distal spinal cord in both OEG and SCs transplanted rats. These included the raphe, reticular and vestibular systems. Further pairwise multiple comparison tests also showed a statistically significant increase in raphe projecting neurons in OEG transplanted rats when compared to SCs transplanted animals. Immunohistochemistry of spinal cord sections short term (2 weeks) and long term (4 months) showed differences in host glial activity, migration and proteoglycan deposits between the two cell types. Histochemical staining revealed that the volume of tissue remaining at the lesion site had increased in all OEG and SCs treated groups. Significant tissue sparing was

  10. Crossed reciprocal inhibition evoked by electrical stimulation of the lamprey spinal cord.

    PubMed

    Fagerstedt, P; Zelenin, P V; Deliagina, T G; Orlovsky, G N; Grillner, S

    2000-09-01

    Activation of a motoneuron pool is often accompanied by inhibition of the antagonistic pool through a system of reciprocal inhibition between the two parts of the neuronal network controlling the antagonistic pools. In the present study, we describe the activity of such a system in the isolated spinal cord of the lamprey, when a tonic motor output is evoked by extracellular stimulation (0.5-1 s train of pulses, 20 Hz) of either end of the spinal cord. With two electrodes symmetrically positioned in relation to the midline, stimulation with either of them separately elicited prolonged (1-5 s) ipsilateral ventral root activity. Activity could be abolished by stronger, simultaneously applied, stimulation of the contralateral side of the cord, suggesting that reciprocal inhibition between hemisegments operates when a tonic motor output is generated. Simultaneous stimulation of both sides of the spinal cord with a single electrode with a large tip (300-400 microm in diameter), positioned over the anatomical midline, elicited inconsistent right-side, leftside, or bilateral ventral root responses. A minor displacement (10-20 microm) to the left or right from the midline resulted in activation of ipsilateral motoneurons, whereas the contralateral motoneurons were silent. These findings indicate that a small asymmetry in the excitatory drive to the left and right spinal hemisegments can be further amplified by reciprocal inhibition between the hemisegments. Longitudinal splitting of the spinal cord along the midline resulted in reduced reciprocal inhibition between the hemisegments separated by the lesion. The reduction was proportional to the extent of the split. The inhibition was abolished when the split reached nine segments in length. From these experiments, the longitudinal distribution of the commissural axons responsible for inhibition of contralateral motor output could be estimated.

  11. Accumulation of p62 in degenerated spinal cord under chronic mechanical compression

    PubMed Central

    Tanabe, Fumito; Yone, Kazunori; Kawabata, Naoya; Sakakima, Harutoshi; Matsuda, Fumiyo; Ishidou, Yasuhiro; Maeda, Shingo; Abematsu, Masahiko; Komiya, Setsuro

    2011-01-01

    Intracellular accumulation of altered proteins, including p62 and ubiquitinated proteins, is the basis of most neurodegenerative disorders. The relationship among the accumulation of altered proteins, autophagy, and spinal cord dysfunction by cervical spondylotic myelopathy has not been clarified. We examined the expression of p62 and autophagy markers in the chronically compressed spinal cord of tiptoe-walking Yoshimura mice. In addition, we examined the expression and roles of p62 and autophagy in hypoxic neuronal cells. Western blot analysis showed the accumulation of p62, ubiquitinated proteins, and microtubule-associated protein 1 light chain 3 (LC3), an autophagic marker, in the compressed spinal cord. Immunohistochemical examinations showed that p62 accumulated in neurons, axons, astrocytes, and oligodendrocytes. Electron microscopy showed the expression of autophagy markers, including autolysosomes and autophagic vesicles, in the compressed spinal cord. These findings suggest the presence of p62 and autophagy in the degenerated compressed spinal cord. Hypoxic stress increased the expression of p62, ubiquitinated proteins, and LC3-II in neuronal cells. In addition, LC3 turnover assay and GFP-LC3 cleavage assay showed that hypoxic stress increased autophagy flux in neuronal cells. These findings suggest that hypoxic stress induces accumulation of p62 and autophagy in neuronal cells. The forced expression of p62 decreased the number of neuronal cells under hypoxic stress. These findings suggest that p62 accumulation under hypoxic stress promotes neuronal cell death. Treatment with 3-methyladenine, an autophagy inhibitor decreased the number of neuronal cells, whereas lithium chloride, an autophagy inducer increased the number of cells under hypoxic stress. These findings suggest that autophagy promotes neuronal cell survival under hypoxic stress. Our findings suggest that pharmacological inducers of autophagy may be useful for treating cervical spondylotic

  12. [Attempts at management of experimental spinal cord hemisection by complete immobilization of the spine in dogs].

    PubMed

    Renard, C

    1980-06-01

    This animal experimentation shows the results of a method aiming at proving the possibilities of medullar reconstruction, if the medullar surfaces are in firm contact ant if medullar tension is neutralized. After hemitransection of the spinal cord, a total spinal immobilization in extension is obtained by using an original orthopaedic prosthesis. Thus, we operated on five dogs, one of which, the reference dog, underwent hemitransection of the spinal cord but no spine immobilization. From a clinical point of view, this dog developed a spastic crural monoplegia, whereas recuperation of motricity by the other dogs was surprising. Histological studies allowed us to observe a certain re-establishment of the spinal cord continuity, suggesting the beginning of an organization of a regeneration mechanism. These statements show the harmful influence of intra-medullar tension for spinal cord reconstruction. In practice, tractions on the spine must be abandoned for they increase the intramedullar tension very much and compromise any eventual "recuperation" after a medullar traumatism.

  13. 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.

  14. 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

  15. Histaminergic Receptors Modulate Spinal Cord Injury-Induced Neuronal Nitric Oxide Synthase Upregulation and Cord Pathology: New Roles of Nanowired Drug Delivery for Neuroprotection.

    PubMed

    Sharma, Hari S; Patnaik, Ranjana; Muresanu, Dafin F; Lafuente, José V; Ozkizilcik, Asya; Tian, Z Ryan; Nozari, Ala; Sharma, Aruna

    2017-01-01

    The possibility that histamine influences the spinal cord pathophysiology following trauma through specific receptor-mediated upregulation of neuronal nitric oxide synthase (nNOS) was examined in a rat model. A focal spinal cord injury (SCI) was inflicted by a longitudinal incision into the right dorsal horn of the T10-11 segments. The animals were allowed to survive 5h. The SCI significantly induced breakdown of the blood-spinal cord barrier to protein tracers, reduced the spinal cord blood flow at 5h, and increased the edema formation and massive upregulation of nNOS expression. Pretreatment with histamine H1 receptor antagonist mepyramine (1mg, 5mg, and 10mg/kg, i.p., 30min before injury) failed to attenuate nNOS expression and spinal cord pathology following SCI. On the other hand, blockade of histamine H2 receptors with cimetidine or ranitidine (1mg, 5mg, or 10mg/kg) significantly reduced these early pathophysiological events and attenuated nNOS expression in a dose-dependent manner. Interestingly, TiO 2 -naowire delivery of cimetidine or ranitidine (5mg doses) exerted superior neuroprotective effects on SCI-induced nNOS expression and cord pathology. It appears that effects of ranitidine were far superior than cimetidine at identical doses in SCI. On the other hand, pretreatment with histamine H3 receptor agonist α-methylhistamine (1mg, 2mg, or 5mg/kg, i.p.) that inhibits histamine synthesis and release in the central nervous system thwarted the spinal cord pathophysiology and nNOS expression when used in lower doses. Interestingly, histamine H3 receptor antagonist thioperamide (1mg, 2mg, or 5mg/kg, i.p.) exacerbated nNOS expression and cord pathology after SCI. These novel observations suggest that blockade of histamine H2 receptors or stimulation of histamine H3 receptors attenuates nNOS expression and induces neuroprotection in SCI. Taken together, our results are the first to demonstrate that histamine-induced pathophysiology of SCI is mediated via n

  16. Spontaneous spinal epidural haematoma: a rare cause of quadriplegia in the post-partum period.

    PubMed

    Bose, S; Ali, Z; Rath, G P; Prabhakar, H

    2007-12-01

    Spontaneous spinal epidural haematoma (SSEH) is a rare cause of neurological deficit in the pregnant and post-partum patients. However, SSEH with associated myelitis presenting as quadriplegia and respiratory paralysis in the post-partum period has never been reported. We report the development of acute onset quadriplegia progressing to respiratory arrest in a 24-yr-old woman 2 weeks after normal vaginal delivery. There was no history suggestive of any coagulopathy (inherited or acquired), eclampsia, pre-existing neurological deficit, or iatrogenic manipulations such as spinal/epidural injections. Magnetic resonance imaging revealed a posterior epidural haematoma extending from C4-C7 and areas of signal changes in spinal cord from cervicomedullary junction to D5 level (suggestive of demyelination). We highlight this rare cause of quadriplegia; focusing on the altered dynamics of the epidural vasculature in the peripartum period leading to SSEH.

  17. Anatomical study of blood supply to the cervical spinal cord in the guinea pig.

    PubMed

    Mazensky, David; Danko, Jan; Petrovova, Eva; Flesarova, Slavka; Supuka, Peter; Supukova, Anna; Luptakova, Lenka; Purzyc, Halina

    2015-06-01

    The aim of this study was to describe the arterial arrangement of the cervical spinal cord in the guinea pig. The study was carried out on 20 adult English self guinea pigs using corrosion and dissection technique. Batson's corrosion casting kit no. 17(©) was used as a casting medium. The origin of the ventral spinal artery from the left vertebral artery was found on average in 35% of the cases and from the right vertebral artery on average in 40% of the cases. The ventral spinal artery with origin from the anastomosis of two medial branches was found on average in 25% of the cases. The presence of ventral radicular branches of rami spinales entering the ventral spinal artery in the cervical region was observed in 42% of the cases on the right side and in 58% of the cases on the left side. The presence of dorsal radicular branches of rami spinales that reached the spinal cord was observed in 63% of the cases on the left side and in 37% of the cases on the right side. The number of radicular branches supplying the spinal cord is greater in guinea pig than in humans. © 2014 Japanese Society of Animal Science.

  18. 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.

  19. Magnetic resonance diffusion tensor imaging of cervical spinal cord and lumbosacral enlargement in patients with cervical spondylotic myelopathy.

    PubMed

    Chen, Xueming; Kong, Chao; Feng, Shiqing; Guan, Hua; Yu, Zhenshan; Cui, Libin; Wang, Yanhui

    2016-06-01

    To identify the correlations of diffusion tensor imaging (DTI) indices between the cervical spinal cord and lumbosacral enlargement in healthy volunteers and patients with cervical spondylotic myelopathy (CSM). DTI was performed at the cervical spinal cord and lumbosacral enlargement in 10 CSM patients and 10 volunteers at 1.5T. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of were measured and compared between CSM patients and volunteers. DTI indices of different cervical segments in volunteers were compared. DTI indices of the cervical spinal cord were correlated with those of the lumbosacral enlargement. In healthy subjects, DTI indices of different cervical cord sections showed no significant difference (ADC: F = 0.62; P = 0.65; FA: F = 1.228; P = 0.312); there was no correlation between the DTI indices of the cervical spinal cord and those of the lumbosacral enlargement (ADC: r = 0.442, P = 0.201; FA: r = -0.054, P = 0.881). In the CSM patients, the ADC value significantly increased, while the FA value significantly decreased in the cervical spinal cord (ADC: P = 0.002; FA: P < 0.001) and lumbosacral enlargement (ADC: P = 0.003; FA: P < 0.001) compared with the healthy group. Both DTI indices showed no correlation between the cervical spinal cord and those of the lumbosacral enlargement in the CSM group (ADC: r = -0.052, P = 0.887; FA: r = 0.129, P = 0.722). The ADC value of the cervical spinal cord and lumbosacral enlargement in CSM patients showed significant increase compared with healthy volunteers, while the FA value significantly decreased. Both DTI indices of the cervical spinal cord had no linear correlation with those of the lumbosacral enlargement. J. Magn. Reson. Imaging 2016;43:1484-1491. © 2015 Wiley Periodicals, Inc.

  20. 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