FUNCTIONAL RECOVERY AFTER CORPECTOMY AND CORTICO CANCELLOUS ILIAC BONE GRAFTING FOR CERVICAL SPINAL CORD INJURY :INITIAL EXPERIENCE.
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ABSTRACT:
SUBMITTER: Sahoo PK
PROVIDER: S-EPMC5531571 | biostudies-other | 1998 Jul
REPOSITORIES: biostudies-other
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Project description:Enabling motor control by epidural electrical stimulation of the spinal cord is a promising therapeutic technique for the recovery of motor function after a spinal cord injury (SCI). Although epidural electrical stimulation has resulted in improvement in hindlimb motor function, it is unknown whether it has any therapeutic benefit for improving forelimb fine motor function after a cervical SCI. We tested whether trains of pulses delivered at spinal cord segments C6 and C8 would facilitate the recovery of forelimb fine motor control after a cervical SCI in rats. Rats were trained to reach and grasp sugar pellets. Immediately after a dorsal funiculus crush at C4, the rats showed significant deficits in forelimb fine motor control. The rats were tested to reach and grasp with and without cervical epidural stimulation for 10weeks post-injury. To determine the best stimulation parameters to activate the cervical spinal networks involved in forelimb motor function, monopolar and bipolar currents were delivered at varying frequencies (20, 40, and 60Hz) concomitant with the reaching and grasping task. We found that cervical epidural stimulation increased reaching and grasping success rates compared to the no stimulation condition. Bipolar stimulation (C6- C8+ and C6+ C8-) produced the largest spinal motor-evoked potentials (sMEPs) and resulted in higher reaching and grasping success rates compared with monopolar stimulation (C6- Ref+ and C8- Ref+). Forelimb performance was similar when tested at stimulation frequencies of 20, 40, and 60Hz. We also found that the EMG activity in most forelimb muscles as well as the co-activation between flexor and extensor muscles increased post-injury. With epidural stimulation, however, this trend was reversed indicating that cervical epidural spinal cord stimulation has therapeutic potential for rehabilitation after a cervical SCI.
| S-EPMC6219872 | biostudies-literature
Project description:Spinal cord injury (SCI) results in rapid and extensive sublesional bone loss. Sclerostin, an osteocyte-derived glycoprotein that negatively regulates intraskeletal Wnt signaling, is elevated after SCI and may represent a mechanism underlying this excessive bone loss. However, it remains unknown whether pharmacologic sclerostin inhibition ameliorates bone loss subsequent to SCI. Our primary purposes were to determine whether a sclerostin antibody (Scl-Ab) prevents hindlimb cancellous bone loss in a rodent SCI model and to compare the effects of a Scl-Ab to that of testosterone-enanthate (TE), an agent that we have previously shown prevents SCI-induced bone loss. Fifty-five (n = 11-19/group) skeletally mature male Sprague-Dawley rats were randomized to receive: (A) SHAM surgery (T8 laminectomy), (B) moderate-severe (250 kilodyne) SCI, (C) 250 kilodyne SCI + TE (7.0 mg/wk, im), or (D) 250 kilodyne SCI + Scl-Ab (25 mg/kg, twice weekly, sc) for 3 weeks. Twenty-one days post-injury, SCI animals exhibited reduced hindlimb cancellous bone volume at the proximal tibia (via μCT and histomorphometry) and distal femur (via μCT), characterized by reduced trabecular number and thickness. SCI also reduced trabecular connectivity and platelike trabecular structures, indicating diminished structural integrity of the remaining cancellous network, and produced deficits in cortical bone (femoral diaphysis) strength. Scl-Ab and TE both prevented SCI-induced cancellous bone loss, albeit via differing mechanisms. Specifically, Scl-Ab increased osteoblast surface and bone formation, indicating direct bone anabolic effects, whereas TE reduced osteoclast surface with minimal effect on bone formation, indicating antiresorptive effects. The deleterious microarchitectural alterations in the trabecular network were also prevented in SCI + Scl-Ab and SCI + TE animals, whereas only Scl-Ab completely prevented the reduction in cortical bone strength. Our findings provide the first evidence indicating that sclerostin inhibition represents a viable treatment to prevent SCI-induced cancellous and cortical bone deficits and provides preliminary rationale for future clinical trials focused on evaluating whether Scl-Ab prevents osteoporosis in the SCI population.
| S-EPMC8367350 | biostudies-literature
Project description:Previously, we and others have shown that rodent neural progenitor cells (NPCs) can support functional recovery after cervical and thoracic transection injuries. To extend these observations to a more clinically relevant model of spinal cord injury, we performed unilateral midcervical contusion injuries in Fischer 344 rats. Two-weeks later, E14-derived syngeneic spinal cord-derived multi-potent NPCs were implanted into the lesion cavity. Control animals received either no grafts or fibroblast grafts. The NPCs differentiated into all three neural lineages (neurons, astrocytes, oligodendrocytes) and robustly extended axons into the host spinal cord caudal and rostral to the lesion. Graft-derived axons grew into host gray matter and expressed synaptic proteins in juxtaposition with host neurons. Animals that received NPC grafts exhibited significant recovery of forelimb motor function compared with the two control groups (analysis of variance p?<?0.05). Thus, NPC grafts improve forelimb motor outcomes after clinically relevant cervical contusion injury. These benefits are observed when grafts are placed two weeks after injury, a time point that is more clinically practical than acute interventions, allowing time for patients to stabilize medically, simplifying enrollment in clinical trials, and enhancing predictability of spontaneous improvement in control groups.
| S-EPMC5908429 | biostudies-literature
Project description:Previous studies suggest locomotion training could be an effective non-invasive therapy after spinal cord injury (SCI) using primarily acute thoracic injuries. However, the majority of SCI patients have chronic cervical injuries. Regaining hand function could significantly increase their quality of life. In this study, we used a clinically relevant chronic cervical contusion to study the therapeutic efficacy of rehabilitation in forelimb functional recovery. Nude rats received a moderate C5 unilateral contusive injury and were then divided into two groups with or without Modified Montoya Staircase (MMS) rehabilitation. For the rehabilitation group, rats were trained 5 days a week starting at 8 weeks post-injury (PI) for 6 weeks. All rats were assessed for skilled forelimb functions with MMS test weekly and for untrained gross forelimb locomotion with grooming and horizontal ladder (HL) tests biweekly. Our results showed that MMS rehabilitation significantly increased the number of pellets taken at 13 and 14 weeks PI and the accuracy rates at 12 to 14 weeks PI. However, there were no significant differences in the grooming scores or the percentage of HL missteps at any time point. Histological analyses revealed that MMS rehabilitation significantly increased the number of serotonergic fibers and the amount of presynaptic terminals around motor neurons in the cervical ventral horns caudal to the injury and reduced glial fibrillary acidic protein (GFAP)-immunoreactive astrogliosis in spinal cords caudal to the lesion. This study shows that MMS rehabilitation can modify the injury environment, promote axonal sprouting and synaptic plasticity, and importantly, improve reaching and grasping functions in the forelimb, supporting the therapeutic potential of task-specific rehabilitation for functional recovery after chronic SCI.
| S-EPMC7266985 | biostudies-literature
Project description:BackgroundThe GEMINI spinal cord fusion protocol has been developed to achieve a successful cephalosomatic anastomosis. Here, we report the preliminary data on the use of a fusogen [polyethylene glycol (PEG)] after full cervical cord transection in mice to facilitate the fusion of both ends of a sharply transected spinal cord.MethodsCervical laminectomy and a complete, visually confirmed cervical cord (C 5) transection was performed on female albino mice (n = 16). In Group 1 (n = 8), a fusogen, (PEG) was used to bridge the gap between the cut ends of the spinal cord. Group 2 received the same spinal cord transection but was treated with saline. Outcome was assessed daily using a standard scale (modified 22-point Basso-Beattie-Bresnahan scale) and filmed on camera.ResultsThe PEG group (group 1) showed partial restoration of motor function after 4 weeks of observation; group 2 (placebo) did not recover any useful motor activity.ConclusionIn this preliminary experiment, PEG, but not saline, promoted partial motor recovery in mice submitted to full cervical transection.
| S-EPMC5025949 | biostudies-literature
Project description:Spinal cord injury (SCI) is a severe condition leading to enduring motor deficits. When lesions are incomplete, promoting spinal cord plasticity might be a useful strategy to elicit functional recovery. Here we investigated whether long-term fluoxetine administration in the drinking water, a treatment recently demonstrated to optimize brain plasticity in several pathological conditions, promotes motor recovery in rats that received a C4 dorsal funiculus crush. We show that fluoxetine administration markedly improved motor functions compared to controls in several behavioral paradigms. The improved functional effects correlated positively with significant sprouting of intact corticospinal fibers and a modulation of the excitation/inhibition balance. Our results suggest a potential application of fluoxetine treatment as a non invasive therapeutic strategy for SCI-associated neuropathologies.
| S-EPMC3713566 | biostudies-literature
Project description:Secondary damage following primary spinal cord injury extends pathology beyond the site of initial trauma, and effective management is imperative for maximizing anatomical and functional recovery. Bisperoxovanadium compounds have proven neuroprotective effects in several central nervous system injury/disease models, however, no mechanism has been linked to such neuroprotection from bisperoxovanadium treatment following spinal trauma. The goal of this study was to assess acute bisperoxovanadium treatment effects on neuroprotection and functional recovery following cervical unilateral contusive spinal cord injury, and investigate a potential mechanism of the compound's action. Two experimental groups of rats were established to 1) assess twice-daily 7 day treatment of the compound, potassium bisperoxo (picolinato) vanadium, on long-term recovery of skilled forelimb activity using a novel food manipulation test, and neuroprotection 6 weeks following injury and 2) elucidate an acute mechanistic link for the action of the drug post-injury. Immunofluorescence and Western blotting were performed to assess cellular signaling 1 day following SCI, and histochemistry and forelimb functional analysis were utilized to assess neuroprotection and recovery 6 weeks after injury. Bisperoxovanadium promoted significant neuroprotection through reduced motorneuron death, increased tissue sparing, and minimized cavity formation in rats. Enhanced forelimb functional ability during a treat-eating assessment was also observed. Additionally, bisperoxovanadium significantly enhanced downstream Akt and mammalian target of rapamycin signaling and reduced autophagic activity, suggesting inhibition of the phosphatase and tensin homologue deleted on chromosome ten as a potential mechanism of bisperoxovanadium action following traumatic spinal cord injury. Overall, this study demonstrates the efficacy of a clinically applicable pharmacological therapy for rapid initiation of neuroprotection post-spinal cord injury, and sheds light on the signaling involved in its action.
| S-EPMC3254642 | biostudies-literature
Project description:Spinal cord injury (SCI) leads to dramatic impairments of motor, sensory, and autonomic functions of affected individuals. Following the primary injury, there is an increased release of glutamate that leads to excitotoxicity and further neuronal death. Therefore, modulating glutamate excitotoxicity seems to be a promising target to promote neuroprotection during the acute phase of the injury. In this study, we evaluated the therapeutic effect of a FDA approved antiepileptic drug (levetiracetam-LEV), known for binding to the synaptic vesicle protein SV2A in the brain and spinal cord. LEV therapy was tested in two models of SCI-one affecting the cervical and other the thoracic level of the spinal cord. The treatment was effective on both SCI models. Treated animals presented significant improvements on gross and fine motor functions. The histological assessment revealed a significant decrease of cavity size, as well as higher neuronal and oligodendrocyte survival on treated animals. Molecular analysis revealed that LEV acts by stabilizing the astrocytes allowing an effective uptake of the excess glutamate from the extracellular space. Overall, our results demonstrate that Levetiracetam may be a promising drug for acute management of SCI.
| S-EPMC7977146 | biostudies-literature
Project description:We tested the ability of two plasticity-promoting approaches to enhance recovery in a mouse model of incomplete spinal cord injury (SCI). Genetically, we reduced myelin-mediated inhibition of neural plasticity through Nogo66-receptor (NgR) gene deletion. Behaviorally, we utilized a novel multimodal exercise training paradigm. Adult mice of wild-type or NgR-null genotype were subjected to partial lateral hemisection (LHx) at C3-C4 with the intent of producing anatomically and functionally mild deficits. Exercise training or control treatment proceeded for 14 weeks. Behavioral outcomes were assessed prior to tract tracing and histological analysis. Genotype and training exerted differing effects on performance; training improved performance on a test related to the training regimen (task-specific benefit), whereas genotype also improved performance on more generalized behaviors (task-non-specific benefit). There were no significant histological differences across genotype or training assignment with regard to lesion size or axonal tract staining. Thus either NgR gene deletion or exercise training benefits mice with mild cervical spinal injury. In this lesion model, the effects of NgR deletion and training were not synergistic for the tasks assessed. Further work is required to optimize the interaction between pharmacological and physical interventions for SCI.
| S-EPMC2978056 | biostudies-literature
Project description:Traumatic human spinal cord injury (SCI) causes devastating and long-term hardships. These are due to the irreparable primary mechanical injury and secondary injury cascade. In particular, oligodendrocyte cell death, white matter axon damage, spared axon demyelination, and the ensuing dysfunction in action potential conduction lead to the initial deficits and impair functional recovery. For these reasons, and that oligodendrocyte and axon survival may be related, various neuroprotective strategies after spinal cord injury are being investigated. We previously demonstrated that oligodendrocytes in the adult rat epicenter ventrolateral funiculus (VLF) express 3'-5'-cyclic adenosine monophosphate-dependent phosphodiesterase 4 (PDE4) subtypes and that their death was attenuated up to 3 days after contusive cervical SCI when rolipram, a specific inhibitor of PDE4, was administered. Here, we report that (1) there are more oligodendrocyte somata in the adult rat epicenter VLF, (2) descending and ascending axonal conductivity in the VLF improves, and that (3) there are fewer hindlimb footfall errors during grid-walking at 5 weeks after contusive cervical SCI when rolipram is delivered for 2 weeks. This is the first demonstration of improved descending and ascending long-tract axonal conductivity across a SCI with this pharmacological approach. Since descending long-tract axonal conductivity did not return to normal, further evaluations of the pharmacokinetics and therapeutic window of rolipram as well as optimal combinations are necessary before consideration for neuroprotection in humans with SCI.
| S-EPMC2760664 | biostudies-literature