Recovery of Locomotion and Skilled Forelimb Function After Spinal Cord Injury in Rats: Effects of Transplants and Neurotrophic Factors (original) (raw)
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The Journal of Neuroscience, 2001
Little axonal regeneration occurs after spinal cord injury in adult mammals. Regrowth of mature CNS axons can be induced, however, by altering the intrinsic capacity of the neurons for growth or by providing a permissive environment at the injury site. Fetal spinal cord transplants and neurotrophins were used to influence axonal regeneration in the adult rat after complete spinal cord transection at a midthoracic level. Transplants were placed into the lesion cavity either immediately after transection (acute injury) or after a 2-4 week delay (delayed or chronic transplants), and either vehicle or neurotrophic factors were administered exogenously via an implanted minipump. Host axons grew into the transplant in all groups. Surprisingly, regeneration from supraspinal pathways and recovery of motor function were dramatically increased when transplants and neurotrophins were delayed until 2-4 weeks after transection rather than applied acutely. Axonal growth back into the spinal cord below the lesion and transplants was seen only in the presence of neurotrophic factors. Furthermore, the restoration of anatomical connections across the injury site was associated with recovery of function with animals exhibiting plantar foot placement and weight-supported stepping. These findings suggest that the opportunity for intervention after spinal cord injury may be greater than originally envisioned and that CNS neurons with long-standing injuries can reinitiate growth, leading to improvement in motor function.
Journal of Applied Animal Research, 2009
Rakei, S.M., Rahmanian, A., Saffarian, A., Shafeian, R. and Mehrabani, D. 2009. Function recovery after transplantation of fetal brain tissue into injured spinal cord in experimental rats. J. Appl. Anim. Res., 36: 303-306.
Motor recovery and anatomical evidence of axonal regrowth in spinal cord-repaired adult rats
Journal of neuropathology and experimental neurology, 2004
Behavioral assessments of hindlimb motor recovery and anatomical assessments of extended axons of long spinal tracts were conducted in adult rats following complete spinal cord transection. Rats were randomly divided into 3 groups: 1) sham control group (laminectomy only; n = 12); 2) transection-only group, spinal cord transection at T8 (n = 20); and 3) experimental treatment group, spinal cord transection at T8, with peripheral nerve grafts (PNG) and application of acidic fibroblast growth factor (aFGF) (n = 14). The locomotor behavior and stepping of all rats were analyzed over a 6-month survival time using the Basso, Beattie, Bresnahan (BBB) open field locomotor test and the contact placing test. Immunohistochemistry for serotonin (5-HT), anterograde tracing with biotinylated dextran amine (BDA), and retrograde tracing with fluoro-gold were used to evaluate the presence of axons below the damage site following treatment. When compared with the transection-only group, the nerve gr...
Neuroscience Bulletin, 2013
Conflicting findings exist regarding the link between functional recovery and the regrowth of spinal tracts across the lesion leading to the restoration of functional contacts. In the present study, we investigated whether functional locomotor recovery was attributable to anatomical regeneration at postnatal day 1 (PN1), PN7, PN14 and in adult rats two months after transection injury at the tenth thoracic segment of the spinal cord. The Basso, Beattie, and Bresnahan scores showed that transection led to a failure of hindlimb locomotor function in PN14 and adult rats. However, PN1 and PN7 rats showed a significant level of stepping function after complete spinal cord transection. Unexpectedly, unlike the transected PN14 and adult rats in which the spinal cord underwent limited secondary degeneration and showed a scar at the lesion site, the rats transected at PN1 and PN7 showed massive secondary degeneration both anterograde and retrograde, leaving a >5-mm gap between the two stumps. Furthermore, retrograde tracing with fluorogold (FG) also showed that FG did not cross the transection site in PN1 and PN7 rats as in PN14 and adult rats, and re-transection of the cord caused no apparent loss in locomotor performance in the rats transected at PN1. Thus, these three lines of evidence strongly indicated that the functional recovery after transection in neonatal rats is independent of regrowth of spinal tracts across the lesion site. Our results support the notion that the recovery of locomotor function in developing rats may be due to intrinsic adaptations in the spinal circuitry below the lesion that control hindlimb locomotor activity rather than the regrowth of spinal tracts across the lesion. The difference in secondary degeneration between neonatal and adult rats remains to be explored.
Purpose: This study investigated whether enrichment improves hindlimb movement following complete spinal cord transection and transplantation of olfactory ensheathing glia (OEG), with or without a Schwann cell (SC) bridge. Methods: Motor activity was encouraged through provision of motor enrichment housing (MEH); a multi-level cage containing ramps, textured surfaces and rewards. Hindlimb joint movement was assessed weekly for 22 weeks starting one week postsurgery, comparing rats housed in MEH to those in basic housing (BH). Transganglionic tracer was injected into the crushed right sciatic nerve three days prior to sacrifice, allowing sensory axons in the dorsal columns to be visualized by immunolabeling. Serotonergic axons and glial cells expressing low affinity nerve growth factor receptor were identified by immunolabeling. Results: All rats, having received transplants, recovered some hindlimb movement. Rats housed in BH progressively lost recovered hindlimb function whereas recovered hindlimb movements were sustained in most rats in MEH. In rats transplanted with SCs and OEG, effects of MEH were first significant 14 weeks after injury. In rats transplanted with OEG, a trend was seen from 14 weeks after injury, but this did not reach significance. In all rats, traced sensory axons died back from sites of transplantation and did not regenerate rostrally. Further, in no rat were serotonergic axons observed regenerating into, around or beyond transplants. Conclusions: Transection and transplantation of SC/OEG or OEG induced recovery of hindlimb function. This recovered hindlimb movement was sustained in rats housed in MEH but was progressively lost in rats housed in BH. Because benefits of MEH were not observed until 14 weeks after injury, long-term assessment of behavior is recommended. BH conditions are not conducive to maintenance of recovered hindlimb function, and MEH should be used in studies of recovery of function following spinal cord injury.
Journal of Neuroscience Research, 2005
Injuries to peripheral nerves are frequent in serious traumas and spinal cord injuries. In addition to surgical approaches, other interventions, such as cell transplantation, should be considered to keep the muscles in good condition until the axons regenerate. In this study, E14.5 rat embryonic spinal cord fetal cells and cultured neural progenitor cells from different spinal cord segments were injected into transected musculocutaneous nerve of 200-300 g female Sprague Dawley (SD) rats, and atrophy in biceps brachii was assessed. Both kinds of cells were able to survive, extend their axons towards the muscle and form neuromuscular junctions that were functional in electromyographic studies. As a result, muscle endplates were preserved and atrophy was reduced. Furthermore, we observed that the fetal cells had a better effect in reducing the muscle atrophy compared to the pure neural progenitor cells, whereas lumbar cells were more beneficial compared to thoracic and cervical cells. In addition, fetal lumbar cells were used to supplement six weeks delayed surgical repair after the nerve transection. Cell transplantation helped to preserve the muscle endplates, which in turn lead to earlier functional recovery seen in behavioral test and electromyography. In conclusion, we were able to show that embryonic spinal cord derived cells, especially the lumbar fetal cells, are beneficial in the treatment of peripheral nerve injuries due to their ability to prevent the muscle atrophy.
Cells Promotes Locomotor Recovery in the Rat Contusion Model of Spinal Cord Injury
2016
Objective: Previous studies have shown that transplantation of bone marrow stromal cells (BMSCs) into the contused spinal cord improves functional recovery and that administration of Schwann cells (SCs) after spinal cord injury (SCI) facilitates axonal regeneration. Although the efficacy of these treatments have been proven, when used individually, their resulting number of regenerated axons is small and locomotor recovery is modest; therefore, we decided to research whether co-transplantation of these cells can improve the outcome. Materials and Methods: Adult male Wistar rats (n=56), each weighting 250-300 grams were used. BMSCs and SCs were cultured and prelabeled with BrdU and 1,1' dioctadecyl 3,3,3',3' tetramethylindocarbocyanin perchlorate respectively. Contusion model of SCI was performed at the T8-9 level using NYU device (New York University device). The rats were divided into seven groups, each consisting of 8 animals. These groups included: a control group, three experimental groups and three sham groups. In the control group, only a laminectomy was performed. The three experiment groups were the BMSC, SC and co-transplant groups, and 7 days after injury, they received intraspinal BMSCs, SCs and the combination of BMSCs & SCs respectively. The sham groups received serum in the same manner. Locomotion in the groups was assessed using the basso, beatie and bresnahan (BBB) test at 1, 7, 14, 21, 28, 35, 42, 49 and 56 days after SCI. Results: More significant improvement was observed in the BBB scores of the co-transplant group (p<0.05) in comparison with BMSC and SC groups. Conclusion: This study shows that co-transplantation of BMSCs and SCs may provide a powerful therapy for SCI and become required for the development of combinatory treatment strategies in the future.