Spinal Cord Injury Lesion Research Articles

Epothilone B impairs functional recovery after spinal cord injury by increasing secretion of macrophage colony-stimulating factor

The microtubule-stabilizing drug epothilone B (epoB) has shown potential value in the treatment of spinal cord injury (SCI) through diverse mechanisms. However, it remains elusive why a limited overall effect was observed. We aim to investigate the limiting factors underlying functional recovery promoted by epoB. The same SCI model treated by epoB was established as discussed previously. We used a cerebrospinal fluid (CSF) sample to assess the changes in cytokines in milieu of the SCI lesion site after epoB treatment. We then analyzed the source of cytokines, the state of microglia/macrophages/monocytes (M/Ms), and the recruitment of neutrophil in the lesion site by using the results of antibody array. Following these findings, we further evaluated the motor functional recovery caused by the reshaped microenvironment. Systemic administration of epoB significantly increased levels of several cytokines in the CSF of the rat SCI model; macrophage colony-stimulating factor (M-CSF) secreted by intact central nervous system (CNS) cells was one of the cytokines with increased levels. Along with epoB and other cytokines, M-CSF reshapes the SCI milieu by activating the microglias, killing bone marrow-derived macrophages, polarizing the M/M to M1 phenotype, and activating downstream cytokines to exacerbate the SCI injury, but it also increases the expression of neurotrophic factors. Anti-inflammatory therapy using a neutralizing antibody mix shows encouraging results. Using in vivo experiments, our findings indicate that epoB inhibits the SCI functional recovery in many ways by reshaping the milieu, which counteracts the therapeutic efficacy that led to the limited overall effectiveness.

Impact of Baseline Magnetic Resonance Imaging on Neurologic, Functional, and Safety Outcomes in Patients With Acute Traumatic Spinal Cord Injury.

Study Design:Systematic review.Objective:To perform a systematic review to evaluate the utility of magnetic resonance imaging (MRI) in patients with acute spinal cord injury (SCI).Methods:An electronic search of Medline, EMBASE, the Cochrane Collaboration Library, and Google Scholar was conducted for literature published through May 12, 2015, to answer key questions associated with the use of MRI in patients with acute SCI.Results:The literature search yielded 796 potentially relevant citations, 8 of which were included in this review. One study used MRI in a protocol to decide on early surgical decompression. The MRI-protocol group showed improved outcomes; however, the quality of evidence was deemed very low due to selection bias. Seven studies reported MRI predictors of neurologic or functional outcomes. There was moderate-quality evidence that longer intramedullary hemorrhage (2 studies) and low-quality evidence that smaller spinal canal diameter at the location of maximal spinal cord compression and the presence of cord swelling are associated with poor neurologic recovery. There was moderate-quality evidence that clinical outcomes are not predicted by SCI lesion length and the presence of cord edema.Conclusions:Certain MRI characteristics appear to be predictive of outcomes in acute SCI, including length of intramedullary hemorrhage (moderate-quality evidence), canal diameter at maximal spinal cord compression (low-quality evidence), and spinal cord swelling (low-quality evidence). Other imaging features were either inconsistently (presence of hemorrhage, maximal canal compromise, and edema length) or not associated with outcomes. The paucity of literature highlights the need for well-designed prospective studies.

A neuropeptide, Substance-P, directly induces tissue-repairing M2 like macrophages by activating the PI3K/Akt/mTOR pathway even in the presence of IFN\u03b3

Macrophage polarization plays an important role in tissue damage and repair. In this study, we show that Substance-P (SP) can directly induce M2 polarization of inflammatory macrophages. SP induced the differentiation of GM-CSF-differentiated pro-inflammatory macrophages into alternatively activated phagocytic M2 like macrophages (M2SP) through direct activation of the PI3K/Akt/mTOR/S6kinase pathway and induction of Arginase-1, CD163, and CD206, all of which were nullified by pretreatment with the neurokinin-1 receptor (NK-1R) antagonist RP67580 and specific signaling pathway inhibitors. M2SP were distinct from IL-4/IL-13-induced M2a and IL-10-induced M2c subtypes; they did not show STAT activation and exhibited high phagocytic and endothelial adhesive activity. Furthermore, SP had a dominant effect on M2 polarization over Interferon gamma (IFNγ), a potent M1-skewing cytokine, and effectively induced the M2 phenotype in monocytes and the human THP-1 cell line. Finally, adoptively transferred M2SP migrated to a spinal cord injury (SCI) lesion site and improved functional recovery. Collectively, our findings show that SP, a neuropeptide, plays a role as a novel cytokine by inducing tissue-repairing M2SP macrophages and thus may be developed for pharmacological intervention in diseases involving chronic inflammation and acute injury.

Cell biology of spinal cord injury and repair.

Spinal cord injury (SCI) lesions present diverse challenges for repair strategies. Anatomically complete injuries require restoration of neural connectivity across lesions. Anatomically incomplete injuries may benefit from augmentation of spontaneous circuit reorganization. Here, we review SCI cell biology, which varies considerably across three different lesion-related tissue compartments: (a) non-neural lesion core, (b) astrocyte scar border, and (c) surrounding spared but reactive neural tissue. After SCI, axon growth and circuit reorganization are determined by neuron-cell-autonomous mechanisms and by interactions among neurons, glia, and immune and other cells. These interactions are shaped by both the presence and the absence of growth-modulating molecules, which vary markedly in different lesion compartments. The emerging understanding of how SCI cell biology differs across lesion compartments is fundamental to developing rationally targeted repair strategies.

Transplantation of human bone marrow-derived clonal mesenchymal stem cells reduces fibrotic scar formation in a rat spinal cord injury model.

This study aimed to evaluate the therapeutic effect on tissue repair and scar formation of human bone marrow-derived clonal mesenchymal stem cells (hcMSCs) homogeneously isolated by using a subfractionation culturing method, in comparison with the non-clonal MSCs (hMSCs), in a rat spinal cord injury (SCI) model. The SCI was made using a vascular clip at the T9 level. Cells were transplanted into the lesion site 3days after injury. A functional test was performed over 4weeks employing a BBB score. Rats were killed for histological analysis at 3days, 1week and 4weeks after injury. The transplantation of hMSCs and hcMSCs significantly reduced lesion size and the fluid-filled cavity at 4weeks in comparison with the control group injected with phosphate buffered saline (PBS) (p<0.01). Transplantation of hcMSCs showed more axons reserved than that of hMSCs in the lesion epicentre filled with non-neuronal tissues. In addition, hMSCs and hcMSCs clearly reduced the inflammatory reaction and intraparenchymal hemorrhaging, compared with the PBS group. Interestingly, hcMSCs largely decreased Col IV expression, one of the markers of fibrotic scars. hcMSCs yielded therapeutic effects more than equal to those of hMSCs on the SCI. Both hMSCs and hcMSCs created an increase in axon regeneration and reduced scar formation around the SCI lesion. Copyright © 2017 John Wiley & Sons, Ltd.

Survival, differentiation and migration of the spinal cord derived neural stem cells from transgenic mice transplanted into mouse models of spinal cord injury

Objective To observe the mice motion recovery and neural stem cell (NSCs) survival, migration and differentiation after the green fluorescent protein (GFP)+ -positive NSCs which was isolated and cultivated from mouse embryonic spinal cord was transplanted into mouse models of spinal cord injury lesions. Methods mice were randomly divided into control group (n=10), injury group (n=30) and cell transplanted group (n=30). The NSCs were transplanted into spinal cord injury after establishing the injured models. The Basso-Beattie-Bresnahan (BBB) function scores, inclined plane test and immunohistochemistry testing were respectively evaluated and recorded 1, 2, 4, 6, 8 weeks after the operation. Results The mouse hind limbs were paralyzed after hitting and BBB scores were 0. The transplanted group increased to 4.50 ± 1.04, injury group was 2.17 ± 0.75, scores began to appear differences at 2 weeks (P=0.023). The scores of transplanted group was 8.17±1.47 and injury group was 5.33±1.03 at 4 weeks (P=0.015). The scores of two groups were increased with the passage of time after 4 weeks. The scores of transplanted group was 10.8±1.47 and injury group was 8.33±0.81 at 6 weeks (P=0.017). The difference was biggest at 8 weeks, transplanted group was 15.50±1.37 and injury group was 11.17±1.16 (P=0.016). The angle of transplanted group was (17.17±3.18)°and injury group was (14.83±3.06)° at 1 weeks. At 2 weeks, the angle of transplanted group was (23.33±4.27)°and injury group was (18.17±2.40)°. The two groups’ results appeared significant differences at 4 weeks in inclined plane test (P=0.024). The transplanted group was (33.83±6.30)°, injury group was (23.50±1.76)°(P=0.029). The small difference of The difference was biggest at 8 weeks, transplanted group was (46.83±6.05)° and injury group was (36.33±7.23)°(P=0.019). The transplanted NSCs can survive and migrate in the body, some of which can remain undifferentiated state, a small part of which can differentiate into glia, less of which differentiate into neurons. Conclusion There was a promoting effect of NSCs for the recovery of spinal cord injury. It was forming a micro-environment conducive to resume by transplanting cells and increasing the proportion of neurons to promote recovery. Key words: Green fluorescent protein; Neural stem cells; Spinal cord injury; Cell transplantation; Mouses

Cetuximab modified collagen scaffold directs neurogenesis of injury-activated endogenous neural stem cells for acute spinal cord injury repair.

Studies have shown that endogenous neural stem cells (NSCs) activated by spinal cord injury (SCI) primarily generate astrocytes to form glial scar. The NSCs do not differentiate into neurons because of the adverse microenvironment. In this study, we defined the activation timeline of endogenous NSCs in rats with severe SCI. These injury-activated NSCs then migrated into the lesion site. Cetuximab, an EGFR signaling antagonist, significantly increased neurogenesis in the lesion site. Meanwhile, implanting cetuximab modified linear ordered collagen scaffolds (LOCS) into SCI lesion sites in dogs resulted in neuronal regeneration, including neuronal differentiation, maturation, myelination, and synapse formation. The neuronal regeneration eventually led to a significant locomotion recovery. Furthermore, LOCS implantation could also greatly decrease chondroitin sulfate proteoglycan (CSPG) deposition at the lesion site. These findings suggest that endogenous neurogenesis following acute complete SCI is achievable in species ranging from rodents to large animals via functional scaffold implantation. LOCS-based Cetuximab delivery system has a promising therapeutic effect on activating endogenous neurogenesis, reducing CSPGs deposition and improving motor function recovery.

Intrathecal transplantation of olfactory ensheathing cells by lumbar puncture for thoracic spinal cord injury in mice

Intrathecal transplantation of olfactory ensheathing cells by lumbar puncture for thoracic spinal cord injury in mice Tao Liu,* Zhongqing Ji,* Shaik Mohammed Ahsan, Yu Zhang, Peng Zhang, Zhihai Fan, Yixin Shen Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China *These authors contributed equally to this work Objectives: To investigate the distribution and function of olfactory ensheathing cells (OECs) following lumbar puncture (LP) transplantation in mouse spinal cord injury (SCI).Methods: OECs were transplanted by LP at level L3–5, 1 week after transected SCI at T8 vertebra. Mice were killed at 3, 21, and 56 days after LP transplantation, and the relative distribution of cells at T8 vertebra was quantitated. The injured spine was also tested by immunohistochemistry to assess neuron regeneration and scar bridging at 8 weeks posttransplantation. Motor functions of mice were evaluated during the observation period using the Basso Mouse Scale.Results: OECs were examined and confirmed by studying cell morphology under phase contrast and immunostaining of NGFR p75. LP-transplanted OECs could be detected just 3 days after transplantation (p75+ area: 0.16 mm2) and accumulated to 0.31 and 0.30 mm2 at 21 and 56 days postengraftment, respectively. The number of endogenous neurons, −400 to +400 µm, far from the epicenter, in OEC-transplanted mice was more than that in SCI mice without engraftment. SCI lesion of mice in the control group (164.3±3.97 µm) was much longer than that in OEC-grafted group (116.7±3.60 µm). Grafts of OECs induced significant functional improvement in mice that underwent T8 vertebral transection, just from 3 days after cell injection.Conclusion: LP is a minimally invasive method for OEC transplantation to treat SCI. This is the first study to visualize the distribution and functions of LP-transplanted OECs in the intact and injured spinal cord. Keywords: olfactory ensheathing cells, spinal cord injury, intrathecal transplantation, lumbar puncture, neuron regeneration, scar bridging

Against the odds: what to expect in rehabilitation of chronic spinal cord injury with a neurologically controlled Hybrid Assistive Limb exoskeleton. A subgroup analysis of 55 patients according to age and lesion level.

Objective Age and lesion level are believed to represent outcome predictors in rehabilitation of patients with chronic spinal cord injury (SCI). The Hybrid Assistive Limb (HAL) exoskeleton enables patients to perform a voluntary controlled gait pattern via an electromyography-triggered neuromuscular feedback system, and has been introduced as a temporary gait training tool in patients with SCI. The aim of this prospective pre- and postintervention study was to examine functional outcomes as a function of age and lesion level in patients with chronic incomplete SCI (iSCI) or chronic complete SCI (cSCI) with zones of partial preservation (ZPP) by using the HAL as a temporary training tool. Methods Fifty-five participants with chronic iSCI or cSCI (mean time since injury 6.85 ± 5.12 years) were classified according to the American Spinal Injury Association (ASIA) Impairment Scale (AIS) and divided by age (< 50 or ≥ 50 years), independent of lesion level, and also into 4 homogeneous groups according to lesion level. The subgroups were as follows: Subgroup 1, tetraplegic iSCI (n = 13) (C2-8, AIS C [n = 8] and AIS D [n = 5]); Subgroup 2, paraplegic iSCI with spastic motor behavior (n = 15) (T2-12, AIS C [n = 8] and AIS D [n = 7]); Subgroup 3, paraplegic cSCI with complete motor paraplegia and absence of spastic motor behavior (n = 18) (T11-L4 [AIS A], and ZPP from L-3 to S-1); and Subgroup 4, paraplegic iSCI with absence of spastic motor behavior (n = 9) (T12-L3, AIS C [n = 8] and AIS D [n = 1]). The training paradigm consisted of 12 weeks of HAL-assisted treadmill training (5 times/week). Baseline status was documented prior to intervention by using the AIS grade, Walking Index for SCI II (WISCI II) score, the 10-meter walk test (10MWT), and the 6-minute walk test (6MinWT). Training effects were assessed after 6 and 12 weeks of therapy, without HAL assistance. Results Overall, a time reduction of 47% in the 10MWT, self-selected speed (10MWTsss) (< 50 years = 56% vs ≥ 50 years = 37%) and an increase of 50% in the 6MinWT were documented. The WISCI II scores showed a mean gain of 1.69 levels. At the end of the study, 24 of 55 patients (43.6%) were less dependent on walking aids. Age had a nonsignificant negative influence on the 10MWTsss. Despite a few nonsignificant subgroup differences, participants improved across all tests. Namely, patients with iSCI who had spastic motor behavior improved to a nonsignificant, lesser extent in the 6MinWT. Conclusions The HAL-assisted treadmill training leads to functional improvements in chronic iSCI or cSCI, both in and out of the exoskeleton. An improvement of approximately 50% in the 10MWTsss and in gait endurance (6MinWT) can be expected from such training. The influences of SCI lesion level and age on functional outcome were nonsignificant in the present study. Older age (≥ 50 years) may be associated with smaller improvements in the 10MWTsss. An iSCI in paraplegic patients with spastic motor behavior may be a nonsignificant negative predictor in gait endurance improvements. Clinical trial registration no.: DRKS00010250 ( https://drks-neu.uniklinik-freiburg.de/drks_web/setLocale_DE.do ).

Anatomical mechanism of spontaneous recovery in regions caudal to thoracic spinal cord injury lesions in rats

BackgroundThe nerve fibre circuits around a lesion play a major role in the spontaneous recovery process after spinal cord hemisection in rats. The aim of the present study was to answer the following question: in the re-control process, do all spinal cord nerves below the lesion site participate, or do the spinal cord nerves of only one vertebral segment have a role in repair?MethodsFirst we made a T7 spinal cord hemisection in 50 rats. Eight weeks later, they were divided into three groups based on distinct second operations at T7: ipsilateral hemisection operation, contralateral hemisection, or transection. We then tested recovery of hindlimbs for another eight weeks. The first step was to confirm the lesion had role or not in the spontaneous recovery process. Secondly, we performed T7 spinal cord hemisections in 125 rats. Eight weeks later, we performed a second single hemisection on the ipsilateral side at T8–T12 and then tested hindlimb recovery for another six weeks.ResultsIn the first part, the Basso, Beattie, Bresnahan (BBB) scores and the electrophysiology tests of both hindlimbs weren’t significantly different after the second hemisection of the ipsilateral side. In the second part, the closer the second hemisection was to T12, the more substantial the resulting impairment in BBB score tests and prolonged latency periods.ConclusionsThe nerve regeneration from the lesion area after hemisection has no effect on spontaneous recovery of the spinal cord. Repair is carried out by all vertebrae caudal and ipsilateral to the lesion, with T12 being most important.

25(OH)D Status of Elite Athletes with Spinal Cord Injury Relative to Lifestyle Factors.

Background: Due to the potential negative impact of low Vitamin D status on performance-related factors and the higher risk of low Vitamin D status in Spinal Cord Injury (SCI) population, research is warranted to determine whether elite athletes with SCI have sufficient 25(OH)D levels. The purposes of this study were to examine: (1) the seasonal proportion of vitamin D insufficiency among elite athletes with SCI; and (2) to determine whether lifestyle factors, SCI lesion level, and muscle performance/function are related to vitamin D status in athletes with SCI. Methods: Thirty-nine members of the Canadian Wheelchair Sports Association, and the US Olympic Committee Paralympic program from outdoor and indoor sports were recruited for this study. Dietary and lifestyle factors, and serum 25(OH)D concentrations were assessed during the autumn (October) and winter (February/March). An independent t-test was used to assess differences in 25(OH)D status among seasons, and indoor and outdoor sports in the autumn and winter, respectively. Results: Mean ± SD serum 25(OH)D concentration was 69.6 ± 19.7 nmol/L (range from 30 to 107.3 nmol/L) and 67.4 ± 25.5 nmol/L (range from 20 to 117.3 nmol/L)in the autumn and winter, respectively. In the autumn, 15.4% of participants were considered vitamin D deficient (25(OH)D < 50 nmol/L) whereas 51.3% had 25(OH)D concentrations that would be considered insufficient (<80 nmol/L). In the winter, 15.4% were deficient while 41% of all participants were considered vitamin D insufficient. Conclusion: A substantial proportion of elite athletes with SCI have insufficient (41%–51%) and deficient (15.4%) 25(OH)D status in the autumn and winter. Furthermore, a seasonal decline in vitamin D status was not observed in the current study.

Astrocyte scar formation aids central nervous system axon regeneration.

Transected axons fail to regrow in the mature central nervous system. Astrocytic scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or ablating chronic astrocytic scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. By contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocytic scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth-supporting molecules. Our findings show that contrary to the prevailing dogma, astrocyte scar formation aids rather than prevents central nervous system axon regeneration.

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

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.

Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair.

Restoration of lost neuronal function after spinal cord injury (SCI) still remains a big challenge for current medicine. One important repair strategy is bridging the SCI lesion with a supportive and stimulatory milieu that would enable axonal rewiring. Injectable extracellular matrix (ECM)-derived hydrogels have been recently reported to have neurotrophic potential in vitro. In this study, we evaluated the presumed neuroregenerative properties of ECM hydrogels in vivo in the acute model of SCI. ECM hydrogels were prepared by decellularization of porcine spinal cord (SC) or porcine urinary bladder (UB), and injected into a spinal cord hemisection cavity. Histological analysis and real-time qPCR were performed at 2, 4, and 8 weeks postinjection. Both types of hydrogels integrated into the lesion and stimulated neovascularization and axonal ingrowth into the lesion. On the other hand, massive infiltration of macrophages into the lesion and rapid hydrogel degradation did not prevent cyst formation, which progressively developed over 8 weeks. No significant differences were found between SC-ECM and UB-ECM. Gene expression analysis revealed significant downregulation of genes related to immune response and inflammation in both hydrogel types at 2 weeks post SCI. A combination of human mesenchymal stem cells with SC-ECM did not further promote ingrowth of axons and blood vessels into the lesion, when compared with the SC-ECM hydrogel alone. In conclusion, both ECM hydrogels bridged the lesion cavity, modulated the innate immune response, and provided the benefit of a stimulatory substrate for in vivo neural tissue regeneration. However, fast hydrogel degradation might be a limiting factor for the use of native ECM hydrogels in the treatment of acute SCI.

Anorectal Manometric and Urodynamic Parameters According to the Spinal Cord Injury Lesion.

ObjectiveTo assess the correlation between the anorectal function and bladder detrusor function in patients with complete spinal cord injury (SCI) according to the type of lesion.MethodsMedical records of twenty-eight patients with SCI were included in this study. We compared the anorectal manometric and urodynamic (UD) parameters in total subjects. We analyzed the anorectal manometric and UD parameters between the two groups: upper motor neuron (UMN) lesion and lower motor neuron (LMN) lesion. In addition, we reclassified the total subjects into two groups according to the bladder detrusor function: overactive and non-overactive.ResultsIn the group with LMN lesion, the mean value of maximal anal squeeze pressure (MSP) was slightly higher than that in the group with UMN lesion, and the ratio of MSP to maximal anal resting pressure (MRP) was statistically significant different between the two groups. In addition, although the mean value of MSP was slightly higher in the group with non-overactive detrusor function, there was no statistical correlation of anorectal manometric parameters between the groups with overactive and non-overactive detrusor function.ConclusionThe MSP and the ratio of MSP to MRP were higher in the group with LMN lesion. In this study, we could not identify the correlation between bladder and bowel function in total subjects. We conclude that the results of UD study alone cannot predict the outcome of anorectal manometry in patients with SCI. Therefore, it is recommended to perform assessment of anorectal function with anorectal manometry in patients with SCI.

Text input speed in people with cervical spinal cord injury

The aim of this prospective clinical study is to determine text input speed (TIS) in people with cervical Spinal Cord Injury (SCI) and to study the influence of participant's characteristics on TIS. People with cervical SCI were included if their level of injury was between C4 and C8 Asia AIS A or B, and were computer users. Each participant underwent a single evaluation using their usual computer access devices. TIS was evaluated during a 10-minute copying task. The relationship between participant's characteristics, computer access device and TIS were analyzed using a Two-Way ANOVA. In the study, 35 participants with cervical SCI and 21 able-bodied people were included. Participants with cervical SCI had a Median TIS was 11 [8.1; 17.2] wpm and able-bodied participants of 23.5 [18.1; 29.7] wpm ( p = 0.001). Participants with SCI lesions at or above C5 had a median TIS of 12.2 [4.5; 13] wpm and those with lesions below C5 had a median TIS of 10.4 [9.2; 18] wpm ( p = 0.38). The Two-Way ANOVA showed that only the type of computer access device significantly influence TIS. Surprisingly, none of the subject's characteristics among them the level of cervical lesion did not affect TIS.

Intravenous Infusion of Ginsenoside Rb1 Ameliorates Compressive Spinal Cord Injury through Upregulation of Bcl-xL and VEGF

Background: Red ginseng root (Panax Ginseng C.A. Meyer) has been used clinically by many Asian people for thousands of years without any detrimental effects. One of the major components of red ginseng root is ginsenoside Rb1 (gRb1, C54H92O23, molecular weight 1109.46). Previously, we showed that intravenous infusion of gRb1 attenuated ischemic brain damage in rats through up-regulation of an anti-apoptotic factor, Bcl-xL. In the present study, we have investigated whether intravenous infusion of gRb1attenuates spinal cord injury or not. Methods: Adult male Wistar rats aged 12-14 weeks, weighing 250-300g, were used. Spinal cord injury (SCI) was induced by compressing the thoracic cord (Th12) with a 20 g weight for 20 minutes. Thirty minutes later, a total of 60µl gRb1 solution (12 or 60µg/60µl in saline) or the same volume of vehicle (saline) was infused once into the left femoral vein. Subsequently, continuous intravenous administration of gRb1 was performed for 7 days. The locomotor function was assessed using the Basso-BeattieBresnahan (BBB) score and the open field test at 1, 3 or 7days after SCI. The animals were killed at 7 days after SCI and the SCI lesions were assessed histologically. Results: Post-traumatic intravenous infusion of gRb1 (12µg/day or 60µg/day) ameliorated BBB score, rearing activity and neuronal density in the anterior horn of the damaged spinal cord at 7 days after SCI. Subsequent studies that focused on gRb1-induced expression of gene products responsible for neuronal death or survival revealed that gRb1 upregulated the expression of not only Bcl-x L , but also a potent angiogenic and neurotrophic factor, vascular endothelial growth factor (VEGF) at 7 days after SCI. Conclusion: Ginsenoside Rb1 (gRb1), with putative anti-apoptotic, angiogenic and neurotrophic actions, is a candidate agent for the treatment of patients with acute SCI.

Positively Charged Oligo[Poly(Ethylene Glycol) Fumarate] Scaffold Implantation Results in a Permissive Lesion Environment after Spinal Cord Injury in Rat.

Positively charged oligo[poly(ethylene glycol) fumarate] (OPF+) scaffolds loaded with Schwann cells bridge spinal cord injury (SCI) lesions and support axonal regeneration in rat. The regeneration achieved is not sufficient for inducing functional recovery. Attempts to increase regeneration would benefit from understanding the effects of the scaffold and transplanted cells on lesion environment. We conducted morphometric and stereological analysis of lesions in rats implanted with OPF+ scaffolds with or without loaded Schwann cells 1, 2, 3, 4, and 8 weeks after thoracic spinal cord transection. No differences were found in collagen scarring, cyst formation, astrocyte reactivity, myelin debris, or chondroitin sulfate proteoglycan (CSPG) accumulation. However, when scaffold-implanted animals were compared with animals with transection injuries only, these barriers to regeneration were significantly reduced, accompanied by increased activated macrophages/microglia. This distinctive and regeneration permissive tissue reaction to scaffold implantation was independent of Schwann cell transplantation. Although the tissue reaction was beneficial in the short term, we observed a chronic fibrotic host response, resulting in scaffolds surrounded by collagen at 8 weeks. This study demonstrates that an appropriate biomaterial scaffold improves the environment for regeneration. Future targeting of the host fibrotic response may allow increased axonal regeneration and functional recovery.

Diaphragmatic Reinnervation in Ventilator-Dependent Patients with Cervical Spinal Cord Injury and Concomitant Phrenic Nerve Lesions Using Simultaneous Nerve Transfers and Implantable Neurostimulators

Patients who are ventilator dependent as a result of combined cervical spinal cord injury and phrenic nerve lesions are generally considered to be unsuitable candidates for diaphragmatic pacing due to loss of phrenic nerve integrity and denervation of the diaphragm. There is limited data regarding efficacy of simultaneous nerve transfers and diaphragmatic pacemakers in the treatment of this patient population. A retrospective review was conducted of 14 consecutive patients with combined lesions of the cervical spinal cord and phrenic nerves, and with complete ventilator dependence, who were treated with simultaneous microsurgical nerve transfer and implantation of diaphragmatic pacemakers. Parameters of interest included time to recovery of diaphragm electromyographic activity, average time pacing without the ventilator, and percent reduction in ventilator dependence. Recovery of diaphragm electromyographic activity was demonstrated in 13 of 14 (93%) patients. Eight of these 13 (62%) patients achieved sustainable periods (> 1 h/d) of ventilator weaning (mean = 10 h/d [n = 8]). Two patients recovered voluntary control of diaphragmatic activity and regained the capacity for spontaneous respiration. The one patient who did not exhibit diaphragmatic reinnervation remains within 12 months of initial treatment. Surgical intervention resulted in a 25% reduction (p < 0.05) in ventilator dependency. We have demonstrated that simultaneous nerve transfers and pacemaker implantation can result in reinnervation of the diaphragm and lead to successful ventilator weaning. Our favorable outcomes support consideration of this surgical method for appropriate patients who would otherwise have no alternative therapy to achieve sustained periods of ventilator independence.

Physiological Performance Determinants of a 22-km Handbiking Time Trial.

To investigate physiological performance determinants of the partial laps and an overall 22-km handbiking (HB) time trial in athletes with high paraplegia. Seven male HB athletes with spinal cord injury (lesion levels thoracic 2-8) performed a laboratory maximal incremental test under cardiorespiratory-mechanical monitoring including respiratory-exchange ratio (RER), oxygen uptake (VO2), and mechanical power output (PO). Individual first and second ventilatory thresholds (VO 2VT1 and VO 2VT2), VO 2peak, and PO peak were posteriorly identified. Athletes also performed a simulated HB time trial along a 4-lap bike circuit under cardiorespiratory measurement. Overall metabolic cost (C) and %VO 2peak (ratio of VO2 to VO 2peak) were calculated from race data. Race performance was defined as mean race velocity (v). athletes completed the 22-km HB time trial in 45 ± 6 min, at 29.9 ± 3.6 km/h, with %VO 2peak = 0.86 ± 0.10 and RER = 1.07 ± 0.17. VO 2peak (r = .89, P = .01), POpeak (r = .85, P = .02), VO 2VT1 (r = .96, P = .001), VO 2VT2 (r = .92, P = .003), and C (2nd lap, r = .78; 3rd lap, r = .80; and 4th lap, r = .80) were significantly (P < .05) positively correlated with race performance. Within-subjects correlation coefficient revealed a large and significant (r = .68, P < .001) relationship between %VO 2peak and v. VO 2peak, PO peak, ventilatory thresholds, %VO 2peak, and C appeared to be important physiological performance determinants of HB time trial.