Setting Of Spinal Cord Injury Research Articles

Treatment of spinal cord injury with intravenous immunoglobulin G: preliminary evidence and future perspectives.

Neuroinflammation plays an important role in the secondary pathophysiological mechanisms of spinal cord injury (SCI) and can exacerbate the primary trauma and thus worsen recovery. Although some aspects of the immune response are beneficial, it is thought that leukocyte recruitment and activation in the acute phase of injury results in the production of cytotoxic substances that are harmful to the nervous tissue. Therefore, suppression of excessive inflammation in the spinal cord could serve as a therapeutic strategy to attenuate tissue damage. The immunosuppressant methylprednisolone has been used in the setting of SCI, but there are complications which have attenuated the initial enthusiasm. Hence, there is interest in other immunomodulatory approaches, such as intravenous Immunoglobulin G (IVIg). Importantly, IVIg is used clinically for the treatment of several auto-immune neuropathies, such as Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIPD) and Kawasaki disease, with a good safety profile. Thus, it is a promising treatment candidate for SCI. Indeed, IVIg has been shown by our team to attenuate the immune response and result in improved neurobehavioral recovery following cervical SCI in rats through a mechanism that involves the attenuation of neutrophil recruitment and reduction in the levels of cytokines and cytotoxic enzymes Nguyen et al. (J Neuroinflammation 9:224, 2012). Here we review published data in the context of relevant mechanisms of action that have been proposed for IVIg in other conditions. We hope that this discussion will trigger future research to provide supporting evidence for the efficiency and detailed mechanisms of action of this promising drug in the treatment of SCI, and to facilitate its clinical translation.

Content validity of the Work Rehabilitation Questionnaire-Self-Report Version WORQ-SELF in a subgroup of spinal cord injury patients

Mixed methods study design. The Work Rehabilitation Questionnaire-Self-Report Version (WORQ-SELF) is an assessment tool based on the International Classification of Functioning, Disability and Health (ICF) developed to evaluate functioning in different patient populations in vocational rehabilitation (VR) settings. The objective of this study is to establish the content validity of WORQ-SELF in a subgroup of spinal cord injury (SCI) patients in the early post-acute context. Swiss Paraplegic Research and Swiss Paraplegic Centre, Nottwil, Switzerland. Contents of WORQ-SELF were compared with semi-guided interviews with SCI patients in Switzerland, the Comprehensive ICF Core Set for SCI early post-acute, and outcome instruments used in VR and SCI. A frequency analysis was performed. WORQ-SELF represented 46 different ICF categories and of these 37 categories were confirmed by the patient interviews. The Comprehensive ICF Core Set for SCI confirmed 25 categories. Four instruments used in VR and SCI setting were identified. Contents of those instruments confirmed 14 categories of WORQ-SELF. Overall, 26 categories of the WORQ-SELF were confirmed by at least 2 of the 3 sources, 13 categories by 1 source and 7 were not confirmed by any of the sources. The WORQ-SELF proved to have content validity for utility in patients with SCI within the context of VR. WORQ-SELF can be used to assess the functioning and disability of patients in the return to work process.

Current Practice of Methylprednisolone Administration for Acute Spinal Cord Injury in Germany

Written mail-out survey. To determine current practice in high-dose methylprednisolone succinate (MPSS) administration for treatment of acute spinal cord injury (SCI) in Germany. Reanalysis of the National Acute Spinal Cord Injury Studies (NASCIS) resulted in criticism of the use of high-dose MPSS for treatment of acute SCI. Subsequently, SCI treatment guidelines were revised leading to a reduction in MPSS use across North America. The impact of these revisions on SCI treatment in Germany is not known. A questionnaire was sent to all trauma, orthopedic and neurosurgical departments of German university centers, affiliated teaching hospitals, and specialized SCI care centers. Survey included 6 questions about the administration of MPSS after acute SCI. Three hundred seventy-two respondents completed the survey (response rate: 51% overall, 76% university hospitals, 85% specialized SCI care centers). Overall, 55% of departments that treat SCI prescribe MPSS. Among them, 73% are "frequent" users administering MPSS to more than 50% of their patients. Ten percent prescribe according to NASCIS I, 43% NASCIS II, 33% NASCIS III, and 13% "generic protocols." As justification for MPSS treatment, "effectiveness" ranked before "common practice" and "medicolegal reasons." "Specialized" SCI care centers differ in that (1) MPSS is administered less frequently, (2) NASCIS I doses are not used, and (3) during the past several years, practice patterns are more likely to have shifted away from the treatment of SCI with MPSS. About one-half of the institutions continue to prescribe MPSS in the setting of acute SCI. A need for further education in almost one-fourth of German departments treating acute SCI is demonstrated through responses indicating use of the outdated NASCIS I protocol, a "legal need" or "unchanged MPSS application during the last years." "Specialized" SCI centers are more likely to change their practice in accordance with evolving literature. 3.

Early versus late surgery for traumatic spinal cord injury: the results of a prospective Canadian cohort study

A multicenter Canadian cohort study. The objective of this study is to evaluate the impact of early versus late surgical decompression on motor neurological recovery after traumatic spinal cord injury (SCI). Canadian acute care and SCI rehabilitation facilities. A prospective cohort study of patients within the Ontario Spinal Cord Injury Registry program was performed. We considered SCI patients with an admission American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade of A through D, with magnetic resonance imaging-confirmed spinal cord compression. Grouped analysis was performed comparing the cohort of patients who received early surgery (<24 h after SCI) to those receiving delayed surgery (<24 h after SCI). The primary outcome was the change in ASIA motor score (AMS) occurring between hospital admission and rehabilitation discharge. A total of 35 (41.7%) patients underwent early surgery and 49 (58.3%) underwent late surgery. At admission, there was a greater proportion of patients within the early surgery group with more severe AIS grade A injuries. Of the 55 patients with neurological exam available at rehabilitation discharge, a greater proportion had at least a two-grade AIS improvement in the early-surgery group (P=0.01). The mean improvement in AMS at rehabilitation discharge was 20 points amongst early-surgery patients and 15 points amongst late-surgery patients (P=0.46). In the analysis investigating AMS improvement, adjusted for preoperative status and neurological level, there was a positive effect estimate for early surgical therapy that was statistically significant (P=0.01). The results here add weight to the growing body of literature, which supports the principle of early intervention in the setting of spinal trauma and SCI.

Early versus Delayed Decompression for Traumatic Cervical Spinal Cord Injury: Results of the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS)

BackgroundThere is convincing preclinical evidence that early decompression in the setting of spinal cord injury (SCI) improves neurologic outcomes. However, the effect of early surgical decompression in patients with acute SCI remains uncertain. Our objective was to evaluate the relative effectiveness of early (<24 hours after injury) versus late (≥24 hours after injury) decompressive surgery after traumatic cervical SCI.MethodsWe performed a multicenter, international, prospective cohort study (Surgical Timing in Acute Spinal Cord Injury Study: STASCIS) in adults aged 16–80 with cervical SCI. Enrolment occurred between 2002 and 2009 at 6 North American centers. The primary outcome was ordinal change in ASIA Impairment Scale (AIS) grade at 6 months follow-up. Secondary outcomes included assessments of complications rates and mortality.FindingsA total of 313 patients with acute cervical SCI were enrolled. Of these, 182 underwent early surgery, at a mean of 14.2(±5.4) hours, with the remaining 131 having late surgery, at a mean of 48.3(±29.3) hours. Of the 222 patients with follow-up available at 6 months post injury, 19.8% of patients undergoing early surgery showed a ≥2 grade improvement in AIS compared to 8.8% in the late decompression group (OR = 2.57, 95% CI:1.11,5.97). In the multivariate analysis, adjusted for preoperative neurological status and steroid administration, the odds of at least a 2 grade AIS improvement were 2.8 times higher amongst those who underwent early surgery as compared to those who underwent late surgery (OR = 2.83, 95% CI:1.10,7.28). During the 30 day post injury period, there was 1 mortality in both of the surgical groups. Complications occurred in 24.2% of early surgery patients and 30.5% of late surgery patients (p = 0.21).ConclusionDecompression prior to 24 hours after SCI can be performed safely and is associated with improved neurologic outcome, defined as at least a 2 grade AIS improvement at 6 months follow-up.

Current management review of thoracolumbar cord syndromes

Injuries to the thoracolumbar spine may lead to a complex array of clinical syndromes that result from dysfunction of the anterior motor units, lumbosacral nerve roots, and/or spinal cord. Neurologic dysfunction may manifest in the lower extremities as loss of fine and gross motor function, touch, pain, temperature, and proprioceptive and vibratory sense deficits. Two clinical syndromes sometimes associated with these injuries are conus medullaris syndrome (CMS) and cauda equina syndrome (CES). To review the current management of thoracolumbar spinal cord injuries. Literature review. Index Medicus was used to search the primary literature for articles on thoracolumbar injuries. An emphasis was placed on the current management, controversies, and newer treatment options. After blunt trauma, these syndromes may reflect a continuum of dysfunction rather than a distinct clinical entity. The transitional anatomy at the thoracolumbar junction, where the conus medullaris is present, makes it less likely that a "pure" CMS or CES syndrome will occur and more likely that a "mixed" injury will. Surgical decompression is the mainstay of treatment for incomplete spinal cord injury (SCI) and incomplete CMS and CES. The value of timing of surgical intervention in the setting of incomplete SCI is unclear at this time. This review summarizes the recent information on epidemiology, pathophysiology, diagnosis, and controversies in the management of thoracolumbar neurologic injury syndromes.

Emerging approaches to the surgical management of acute traumatic spinal cord injury.

Traumatic, spinal cord injury (SCI) is a potentially catastrophic event causing major impact at both a personal and societal level. To date, virtually all therapies that have shown promise at the preclinical stage of study have failed to translate into clinically effective treatments. Surgery is performed in the setting of SCI, with the goals of decompressing the spinal cord and restoring spinal stability. Although a consensus regarding the optimal timing of surgical decompression for SCI has not been reached, much of the preclinical and clinical evidence, as well as a recent international survey of spine surgeons, support performing early surgery (<24 hours). Results of the multicenter, Surgical Trial in Acute Spinal Cord Injury Study (STASCIS), expected later this year, should further clarify this important management issue. The overall goal of this review is to provide an update regarding the current status of surgical therapy for traumatic SCI by reviewing relevant pathophysiology, laboratory, and clinical evidence, as well as to introduce radiologic and clinical tools that aid in the surgical decision-making process.

Human Neural Stem Cells Differentiate and Promote Locomotor Recovery in an Early Chronic Spinal coRd Injury NOD-scid Mouse Model

BackgroundTraumatic spinal cord injury (SCI) results in partial or complete paralysis and is characterized by a loss of neurons and oligodendrocytes, axonal injury, and demyelination/dysmyelination of spared axons. Approximately 1,250,000 individuals have chronic SCI in the U.S.; therefore treatment in the chronic stages is highly clinically relevant. Human neural stem cells (hCNS-SCns) were prospectively isolated based on fluorescence-activated cell sorting for a CD133+ and CD24−/lo population from fetal brain, grown as neurospheres, and lineage restricted to generate neurons, oligodendrocytes and astrocytes. hCNS-SCns have recently been transplanted sub-acutely following spinal cord injury and found to promote improved locomotor recovery. We tested the ability of hCNS-SCns transplanted 30 days post SCI to survive, differentiate, migrate, and promote improved locomotor recovery.Methods and FindingshCNS-SCns were transplanted into immunodeficient NOD-scid mice 30 days post spinal cord contusion injury. hCNS-SCns transplanted mice demonstrated significantly improved locomotor recovery compared to vehicle controls using open field locomotor testing and CatWalk gait analysis. Transplanted hCNS-SCns exhibited long-term engraftment, migration, limited proliferation, and differentiation predominantly to oligodendrocytes and neurons. Astrocytic differentiation was rare and mice did not exhibit mechanical allodynia. Furthermore, differentiated hCNS-SCns integrated with the host as demonstrated by co-localization of human cytoplasm with discrete staining for the paranodal marker contactin-associated protein.ConclusionsThe results suggest that hCNS-SCns are capable of surviving, differentiating, and promoting improved locomotor recovery when transplanted into an early chronic injury microenvironment. These data suggest that hCNS-SCns transplantation has efficacy in an early chronic SCI setting and thus expands the “window of opportunity” for intervention.

Research Highlights

Research Highlights

RETRACTED ARTICLE: Therapeutic DNA Vaccination as a Repair Strategy Following Spinal Cord Injury

Myelin-derived proteins, such as tenascin-R (TN-R), myelin associate glycoprotein (MAG), oligodendrocyte-myelin glycoprotein (OMgp), and Nogo-A, inhibit the central nervous system regeneration. In this study, the DNA vaccine encoding for oligodendrocyte and myelin-related antigens was employed to attenuate the axonal growth inhibitory properties of myelin in the setting of spinal cord injury. Using a rat spinal cord dorsal hemisection model, the vaccine directed against the inhibitory epitopes of Nogo-A, MAG, OMgp, and TN-R was administered intramuscularly once a week following spinal cord injury, supplemented with local application of specific anti-sera against the four antigens. Anterograde labeling of dorsal column fibers showed active axonal regeneration through the lesion site at the eighth week following the treatment in experimental group but not in control groups. Light microscopic and ultrastructural analysis revealed that vaccination with these myelin-related antigens did not lead to demyelinating disease. OMgp and TN-R levels were down-regulated at the lesion site together with a parallel increase in growth-associated protein 43 levels in the treatment groups. This study reveals the effective approach of a DNA vaccine strategy by attaining the special antibody to direct neutralization of the myelin inhibitors during spinal cord injury.

Therapeutic hypothermia for spinal cord injury

In this article, the role of modest hypothermia for the treatment of experimental and clinical spinal cord injury (SCI) is discussed. While early investigations evaluated the beneficial effects of more profound levels of local hypothermia treatment following SCI, recent studies have concentrated on the benefits of mild hypothermia in protecting and promoting functional recovery in established animal models. In this regard, using preclinical models of both thoracic and cervical contusive SCI, early cooling strategies using systemically administered mild hypothermia (33 degrees C) have been reported to improve locomotive function as well as forelimb gripping strength and coordination. Recently, the effects of modest hypothermia in severely injured SCI patients have also been tested. Modest systemic hypothermia was reported to be both safe and achievable in severely injured SCI patients. This evidence-based review summarizes both experimental and clinical data to support the use of modest hypothermia in the acute SCI setting.

Involuntary, Electrically Excitable Nerve Transfer for Denervation: Results From an Animal Model

The purpose of this study was to evaluate the efficacy of "paralyzed" nerve transfer (ie, transfer of an involuntary, nondegenerated, electrically excitable nerve onto an involuntary, degenerated, non-electrically excitable nerve) and functional electrical stimulation for reinnervation. We hypothesized that lower motor neuron cell body continuity with the motor cortex, via intact upper motor neurons, is not necessary for reinnervation of the extremities. Fischer 344 rats had lower thoracic spinal cord injury (SCI) followed by unilateral tibial nerve transection and delayed peroneal ("paralyzed") to tibial nerve transfer (group A) or primary neurorrhaphy (group B). Control groups had SCI and a unilateral hindlimb incision and nerve exposure only (group C) or a unilateral hindlimb disection and transection of both the tibial and peroneal nerves (group D). Three months after surgery, the proximal peroneal (group A) or proximal tibial (groups B, C, and D) nerves were electrically stimulated in vivo, and gastrocnemius force production was measured on both the operative and nonoperative hindlimbs. In addition, the distal tibial nerves from both the experimental and control-side hindlimbs were sectioned and stained with anti-neurofilament protein to determine total axon counts. Mean gastrocnemius force return and mean axonal regeneration was 47% and 51%, respectively, for group A animals (n = 9), 68% and 73% for group B animals (n = 4), 97% and 99% for group C animals (n = 4), and 0 and 2% for group D animals (n = 4). A 1-way analysis of variance for independent samples yielded significant differences between groups A, B, and C for gastrocnemius force return and between all groups for axonal regeneration. Paralyzed nerve transfer produces a mean of approximately 50% return of gastrocnemius force and axonal regeneration. Paralyzed nerve transfer combined with functional electrical stimulation is a viable method for reanimating denervated motor units in the setting of SCI.

The role of heat shock proteins in spinal cord injury

Heat shock proteins (HSPs) are normal intracellular proteins that are produced in greater amounts when cells are subjected to stress or injury. These proteins have been shown to play a key role in the modulation of the secondary injury that occurs after the initial spinal cord injury (SCI). Heat shock proteins normally act as molecular chaperones and are called protein guardians because they act to repair partially damaged proteins. Normally intracellular, HSPs can also be liberated into the systemic circulation to act as important inflammatory mediators. In the setting of SCI, HSP induction has been shown to be beneficial. These proteins are liberated primarily by acutely stressed microglial, endothelial, and ependymal cells. Heat shock proteins have also been shown to assist in the protection of motor neurons and to prevent chronic inflammation after SCI. In animal models, several experimental drugs have shown neuroprotective effects in the spinal cord and appear to function by modulating HSPs.

Dietary restriction started after spinal cord injury improves functional recovery

Spinal cord injury typically results in limited functional recovery. Here we investigated whether therapeutic dietary restriction, a multi-faceted, safe, and clinically-feasible treatment, can improve outcome from cervical spinal cord injury. The well-established notion that dietary restriction increases longevity has kindled interest in its potential benefits in injury and disease. When followed for several months prior to insult, prophylactic dietary restriction triggers multiple molecular responses and improves outcome in animal models of stroke and myocardial infarction. However, the efficacy of the clinically-relevant treatment of post-injury dietary restriction is unknown. Here we report that “every-other-day fasting” (EODF), a form of dietary restriction, implemented after rat cervical spinal cord injury was neuroprotective, promoted plasticity, and improved behavioral recovery. Without causing weight loss, EODF improved gait-pattern, forelimb function during ladder-crossing, and vertical exploration. In agreement, EODF preserved neuronal integrity, dramatically reduced lesion volume by > 50%, and increased sprouting of corticospinal axons. As expected, blood β-hydroxybutyrate levels, a ketone known to be neuroprotective, were increased by 2–3 fold on the fasting days. In addition, we found increased ratios of full-length to truncated trkB (receptor for brain-derived neurotrophic factor) in the spinal cord by 2–6 folds at both 5 days (lesion site) and 3 weeks after injury (caudal to lesion site) which may further enhance neuroprotection and plasticity. Because EODF is a safe, non-invasive, and low-cost treatment, it could be readily translated into the clinical setting of spinal cord injury and possibly other insults.

The Use of Botulinum Toxin for Spasticity After Spinal Cord Injury

To describe the use and effects of botulinum toxin (BTX) injections in persons with spinal cord injury (SCI) and focal spasticity. Chart review of patients with SCI receiving their first injection of BTX for spasticity control at a freestanding urban rehabilitation hospital. Charts were reviewed for history and level of SCI, one of five self-identified goals (ambulation, positioning, upper-extremity function, hygiene, and pain control) before and after injection; site and doses of BTX used; and self-reported outcome on clinical follow-up. Charts of 28 adults receiving BTX were reviewed. All patients received BTX type A. Dosages of BTX ranged from 10 to 119 units per muscle. Improvement was noted for 56% in ambulation and 71% in positioning. Overall, upper-extremity function improved in 78%, hygiene improved in 66.6%, and pain decreased in 83.3%. Early use of BTX injections (less than a year after onset of symptoms) vs. late use of BTX injections did not influence effectiveness. BTX seems to be an effective treatment for focal spasticity and for reducing disability in persons with SCI. Randomized trials are needed to confirm the value of this treatment in the setting of SCI.

Stem cell biology and its therapeutic applications in the setting of spinal cord injury

The development of an acute traumatic spinal cord injury (SCI) inevitably leads to a complex cascade of ischemia and inflammation that results in significant scar tissue formation. The development of such scar tissue provides a severe impediment to neural regeneration and healing with restoration of function. A multimodal approach to treatment is required because SCIs occur with differing levels of severity and over different lengths of time. To achieve significant breakthroughs in outcomes, such approaches must combine both neuroprotective and neuroregenerative treatments. Novel techniques modulating endogenous stem cells demonstrate great promise in promoting neuroregeneration and restoring function.

A Quantitative and Reproducible Method to Assess Cord Compression and Canal Stenosis After Cervical Spine Trauma

Reliability study. To assess the intrarater and interrater reliability of a recently described technique to measure of maximum canal compromise (MCC) and maximum spinal cord compression (MSCC) using digitized and magnified images in the setting of traumatic cervical spinal cord injury (SCI). The extent of MCC and MSCC is of clinical and prognostic value in the setting of traumatic cervical SCI. However, concerns remain regarding the accuracy of measurements based on hard copy images. We hypothesized that the interrater and intrarater reliability of these assessments would be enhanced using magnified digitized images and software-based measurement tools. Midsagittal MRI and CT images of cervical spine were selected from 5 individuals with acute traumatic cervical SCI. Measurements of MCC using CT scan and T1-weighted MRI and measurements of MSCC based on T2-weighted MR images were independently estimated by 13 raters on 10 occasions. The intrarater reliability for CT-MCC, T1-weighted MRI-MCC and T2-weighted MRI-MSCC was high in the 10 rounds in each patient. In addition, the mean intrarater interclass correlation coefficient was 0.72 +/- 0.05 for the CT-MCC, 0.70 +/- 0.07 for the T1-weighted MRI-MCC, and 0.68 +/- 0.11 for the T2-weighted MRI-MSCC. The mean interrater interclass correlation coefficients were 0.43 +/- 0.02 for the CT-MCC, 0.61 +/- 0.03 for the T1-weighted MRI-MCC, and 0.55 +/- 0.05 for the evaluation of T2-weighted MRI-MSCC. Our study has demonstrated that the intrarater reliability for the instrument to assess MCC and MSCC in the setting of traumatic SCI was high. The interrater ICCs at a moderate level of reliability combined with our results using analysis of variance with post hoc tests indicate that the measurements of MCC and MSCC are reproducible, which supports the use of these radiologic parameters in the clinical and research settings.

Optimal treatment for severe neurogenic bowel dysfunction after chronic spinal cord injury: a decision analysis

When conservative management fails in patients with chronic spinal cord injury (SCI) and neurogenic bowel dysfunction, clinicians have to choose from a variety of treatment options which include colostomy, ileostomy, Malone anterograde continence enema (MACE) and sacral anterior root stimulator (SARS) implantation. This study employed a decision analysis to examine the optimal treatment for bowel management of young individuals with chronic refractory constipation in the setting of chronic SCI. A decision analysis was created to compare the four surgical strategies using baseline analysis, one-way and two-way sensitivity analyses, 'worst scenario' and 'best scenario' sensitivity analyses, and probabilistic sensitivity analyses. Quality-adjusted life expectancy (QALE) was the primary outcome. The baseline analysis indicated that patients who underwent the MACE procedure had the highest QALE value compared with the other interventions. Sensitivity analyses showed that these results were robust. The MACE procedure may provide the best long-term outcome in terms of the probability of improving bowel function, reducing complication rates and the incidence of autonomic dysreflexia, and being congruent with patients' preferences. The analysis was sensitive to changes in assumptions about quality of life/utility, and thus the results could change if more specific estimates of utility became available.

The Impact of Methylprednisolone on Lesion Severity Following Spinal Cord Injury

Retrospective study comparing spinal cord injury (SCI) lesion characteristics in methylprednisolone (MPS) treated versus untreated patients as demonstrated by magnetic resonance (MR) imaging. Determine if the administration of MPS immediately following SCI affects lesion severity. The administration of MPS in the setting of acute SCI has become controversial. Since magnetic resonance imaging (MRI) is sensitive for the detection of spinal cord edema and hemorrhage, changes in lesion characteristics would support a biologic effect due to MPS. Patients with cervical spinal injury treated with the recommended dose of methylprednisolone (bolus 30 mg/kg + 5.4 mg/kg per hour over 24 hours) initiated within 8 hours of injury were compared to historical controls that did not receive steroids. All patients (n = 82) sustained clinically complete SCI (ASIA Grade A) and underwent MRI on the same 1.5 Tesla unit. The length of spinal cord edema, presence/absence of intramedullary hemorrhage, and length of intramedullary hemorrhage were measured on T2-weighted and gradient echo MR images. Comparisons of lesion severity were then made between untreated and treated subjects. Forty-eight of 82 patients with complete injuries received MPS therapy. After accounting for differences in the mean age of the treatment and control groups, multiple regression analysis demonstrated a persistent reduction in the mean length of intramedullary hemorrhage, 2.6 U in the treatment group versus 4.4 U in the control group (P = 0.04). Although there was a reduction in the number of patients exhibiting spinal cord hemorrhage in the treated group compared with the untreated group (65% vs. 91%), this result was not statistically significant (P = 0.16). There was no statistically significant effect of MPS treatment on the mean length of the spinal cord edema between treated versus untreated subjects (10.3 vs. 12.0, respectively, P = 0.85). MRI suggests MPS therapy in the acute phase of spinal cord injury may decrease the extent of intramedullary spinal cord hemorrhage.

Optimizing the transplant dose of a human neuronal cell line graft to treat SCI pain in the rat

Neuropathic pain is a prevalent and difficult problem in the setting of spinal cord injury (SCI). The use of cellular transplant therapy to treat this pain has been successful with the use of a human neuronal cell line, hNT2.17 [M.J. Eaton, S.Q. Wolfe, M.A. Martinez, M. Hernandez, C. Furst, J. Huang, B.R. Frydel, O. Gomez-Marin, Subarachnoid transplant of a human neuronal cell line attenuates chronic allodynia and hyperalgesia after excitotoxic SCI in the rat, J. Pain 8 (2007) 33–50]. Intrathecal transplant of these cells potently reverses behavioral hypersensitivity after excitotoxic spinal cord injury in the rat model. This study focuses on delineating the optimal dose of these cell grafts in the same model. Two weeks after intraspinal injection of quisqualic acid (QUIS) with subsequent behavioral hypersensitivity, terminally differentiated hNT2.17 cells were transplanted into 300 g Wistar-Furth rats in a logarithmic variation of doses: 10 6, 10 5 and 10 3 cells. Behavioral hypersensitivity testing was performed weekly for 6 weeks following transplant. The dose of 10 6 cells (or approximately 3 million/kg) potently and permanently reversed both cutaneous allodynia (CA) and thermal hyperalgesia (TH). Reduced transplant doses of the hNT2.17 cell line did not permanently reverse behavioral hypersensitivity, suggesting that there is an optimal dose that can be used as a clinical tool to treat SCI-associated neuropathic pain.