The Effects of FK506 on Dorsal Column Axons Following Spinal Cord Injury in Adult Rats: Neuroprotection and Local Regeneration

There is considerable evidence that immunophilin ligands can promote the regeneration of axons in peripheral nerves and act as neuroprotective agents in the CNS. We have examined the effects of FK506 and GPI 1046 on the responses to partial transection of ascending spinal dorsal column axons at T9, in some cases combined with crush of one sciatic nerve. FK506 (0.5 or 2.0 mg/kg) and GPI 1046 (10 or 40 mg/kg) was administered subcutaneously immediately after surgery and five times a week thereafter. Some animals received methylprednisolone (MP) (two subcutaneous doses of 30 mg/kg) in addition to, or instead of, FK506. After survival times of 1-12 weeks, dorsal column axons were labeled transganglionically with cholera toxin B-HRP. There was massive axonal sprouting at the lesion sites in animals with sciatic nerve injury and immunophilin ligand treatment. In FK506-treated animals a few severed sensory axons regenerated for up to 10 mm rostral to the lesion. Of greater significance, 30% of 71 FK506-treated animals had spared axons in the dorsal column, extending to the nucleus gracilis, versus 8% of 50 control animals (P < 0.05), showing that FK506 reduces the likelihood of axonal destruction due to secondary injury. A combination of FK506 and MP afforded greater protection than MP alone (P < 0.05), but axonal survival was not affected by sciatic nerve crush, dose of FK506, or survival time after injury. GPI 1046 (n = 11) did not promote axonal survival. Thus FK506 protects axons from secondary injury following spinal cord trauma, and in this experimental model, its neuroprotective effect is greater than that of MP.     

Olfactory ensheathing glia graft in combination with FK506 administration promote repair after spinal cord injury

The aim of this study was to determine whether a combination of olfactory ensheathing cell (OEC) graft with the administration of FK506, two experimental approaches that have been previously reported to exert protective/regenerative effects after spinal cord injury, promotes synergic restorative effects after complete or partial spinal cord injuries. In partial spinal cord injury, combination of an OEC graft and FK506 reduced functional deficits evaluated by the BBB score, motor-evoked potentials (MEPs) and H reflex tests, diminished cavitation, astrogliosis and increased sparing/regeneration of raphespinal fibers compared to untreated and single-treatment groups of rats. After complete spinal cord transection, the combined treatment significantly improved functional outcomes, promoted axonal regeneration caudal to the lesion, and diminished astrogliosis compared only to non-transplanted animals. Slightly, but non-significant, better functional and histological results were found in OEC-grafted animals treated with FK506 than in those given saline after spinal cord transection. Nevertheless, the combined treatment increased the percentage of rats that recovered MEPs and promoted a significant reduction in astrogliosis. In conclusion, this study demonstrates that OEC grafts combined with FK506 promote additive repair of spinal cord injuries to those exerted by single treatments, the effect being more remarkable when the spinal cord is partially lesioned.     

Nerve fibre regeneration across the PNS-CNS interface at the root-spinal cord junction

Root-spinal cord regeneration was investigated in immature and adult rats. The elongation in the dorsal root of regrowing dorsal root axons, rerouted ventral root nerve fibres (cholinergic neurons) or hypogastric nerve fibres (catecholaminergic neurons) is impeded as they meet the astrocyte dominated CNS tissue of the root. The establishment of synaptoid nerve terminals as the regrowing axons encounter astrocytes indicates a mechanism for growth inhibition other than a physical impediment in the CNS environment. The glial cells of the CNS segment in the root are influenced by the type of regenerating nerve fibres in terms of maintenance, multiplication and phenotypic expression. After a dorsal root lesion in the neonatal rat several root axons may reinnervate the spinal cord. In these rats, the normal establishment of a CNS root segment has been disrupted and the PNS-CNS border is situated central to the root-spinal cord junction. Implantation of cut dorsal roots into the spinal cord of adult rats results in the extension of processes from intrinsic spinal cord neurons out into the root. After implantation of avulsed ventral roots into the ventro-lateral aspect of the cord, axonal regrowth and functional restitution of alpha-motoneurons could be demonstrated by intracellular recordings and injections with horseradish peroxidase. These results show that regeneration can occur across a PNS-CNS interface that has been established secondary to a trauma in the mature animal and in the immature animal before the astrocyte-rich CNS root segment has been developed.     

Regeneration of adult dorsal root axons into transplants of embryonic spinal cord

Transplants of the embryonic rat spinal cord survive and differentiate in the spinal cords of adult and newborn host rats. Very little is known about the extent to which these homotopic transplants can provide an environment for regeneration of adult host axons that normally terminate in the spinal cord. We have used horseradish peroxidase injury filling and transganglionic transport methods to determine whether transected dorsal roots regenerate into fetal spinal cord tissue grafted into the spinal cords of adult rats. Additional transplants were examined for the presence of calcitonin gene-related peptide-like immunoreactivity, which in the normal dorsal horn is derived exclusively from primary afferent axons. Host animals had one side of the L4-5 spinal cord resected and replaced by a transplant of E14 or E15 spinal cord. Adjacent dorsal roots were sectioned and juxtaposed to the graft. The dorsal roots and their projections into the transplants were then labeled 2-9 months later. The tracing methods that used transport or diffusion of horseradish peroxidase demonstrated that severed host dorsal root axons had regenerated and grown into the transplants. In addition, some donor and host neurons had extended their axons into the periphery to at least the midthigh level as indicated by retrograde labeling following application of tracer to the sciatic nerve. Primary afferent axons immunoreactive for calcitonin gene-related peptide were among those that regenerated into transplants, and the projections shown by this immunocytochemical method exceeded those demonstrated by the horseradish peroxidase tracing techniques. Growth of the host dorsal roots into transplants indicates that fetal spinal cord tissue permits regeneration of adult axotomized neurons that would otherwise be aborted at the dorsal root/spinal cord junction. This transplantation model should therefore prove useful in studying the enhancement and specificity of the regrowth of axons that normally terminate in the spinal cord.     

他克莫司促进神经干细胞移植大鼠脊髓损伤的再生与修复

背景：研究证实,他克莫司不仅抑制T细胞的增殖、活化,还能抑制小胶质细胞、巨噬细胞等炎症细胞在损伤局部聚集、活化及相关炎症因子的释放,减轻继发性炎症反应对原发损伤周围正常组织的破坏,从而对损伤局部的神经组织起保护作用。 目的：观察他克莫司对神经干细胞移植大鼠脊髓损伤后再生修复的影响。 方法：分离培养孕13d SD大鼠神经干细胞。显微镜下动脉瘤夹夹闭SD大鼠T8脊髓,建立压迫型脊髓损伤动物模型。损伤后7 d随机数字表分为3组：对照组,于损伤中心定向注射生理盐水;细胞移植组,于损伤中心定向注射神经干细胞;他克莫司组,于损伤中心定向注射神经干细胞同时给予免疫抑制剂他克莫司1 mg/(kg•d)腹腔注射连续7 d。1,2,4,8周后,通过BDA顺行示踪、苏木精-伊红与免疫组化染色及电镜检测,观察移植后脊髓组织再生和神经元的变化。 结果与结论：对照组在损伤中心端远侧无神经纤维通过。细胞移植组与他克莫司组在治疗1周后有部分神经纤维通过,8周均有部分BDA阳性标记的皮质脊髓束再生通过脊髓损伤部位,特别是他克莫司组可延续至距损伤中心1.7 cm 。苏木精-伊红染色显示,细胞移植组与他克莫司组2周时坏死灶开始缩小,泡沫细胞减少。电镜结果显示,他克莫司组1周时即出现较正常的微丝和微管结构,8周时星形细胞、许旺细胞、髓鞘典型多见,神经轴突的终末有较多的兴奋性递质和不典型的轴树连接,出现较多的结构正常的髓鞘。说明损伤大鼠移植神经干细胞后联合应用他克莫司后可减轻早期的急性炎症反应,保证神经细胞的存活,具有神经保护和神经营养作用,可加快神经功能的恢复。     

Enteric glia promote regeneration of transected dorsal root axons into spinal cord of adult rats

After spinal cord injury axonal regeneration is poor, but may be enhanced by the implantation of olfactory ensheathing glia (OEG). Enteric glia (EG) share many properties of OEG. Transected dorsal root axons normally do not regenerate through the central nervous system myelin into the spinal cord. We tested whether EG, like OEG, could promote regeneration in this paradigm. Three weeks after EG implantation, numerous regenerating dorsal root axons reentered the spinal cord. Ingrowth of dorsal root axons was observed using 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate. Primary sensory afferents invaded laminae 1, 2, and 3, grew through laminae 4 and 5, and reached the dorsal gray commissure. No axonal ingrowth was observed in control animals, indicating that transplanted EG enabled regeneration of the injured dorsal root axons into the adult spinal cord. Thus, EG implantation may be beneficial in promoting axonal growth after central nervous system injury.     

Peripheral nerve injury induced changes in the spinal cord and strategies to counteract/enhance the changes to promote nerve regeneration

Peripheral nerve injury leads to morphological, molecular and gene expression changes in the spinal cord and dorsal root ganglia, some of which have positive impact on the survival of neurons and nerve regeneration, while the effect of others is the opposite. It is crucial to take prompt measures to capitalize on the positive effects of these reactions and counteract the negative impact after peripheral nerve injury at the level of spinal cord, especially for peripheral nerve injuries that are severe, located close to the cell body, involve long distance for axons to regrow and happen in immature individuals. Early nerve repair, exogenous supply of neurotrophic factors and Schwann cells can sustain the regeneration inductive environment and enhance the positive changes in neurons. Administration of neurotrophic factors, acetyl-L-carnitine, N-acetyl-cysteine, and N-methyl-D-aspartate receptor antagonist MK-801 can help counteract axotomy-induced neuronal loss and promote regeneration, which are all time-dependent. Sustaining and reactivation of Schwann cells after denervation provides another effective strategy. FK506 can be used to accelerate axonal regeneration of neurons, especially after chronic axotomy. Exploring the axotomy-induced changes after peripheral nerve injury and applying protective and promotional measures in the spinal cord which help to retain a positive functional status for neuron cell bodies will inevitably benefit regeneration of the peripheral nerve and improve functional outcomes.     

NT-3 delivered by an adenoviral vector induces injured dorsal root axons to regenerate into the spinal cord of adult rats

Sensory axons interrupted in the dorsal roots of adult mammals are normally unable to regenerate into the spinal cord. We have investigated whether the introduction of a neurotrophin gene into the spinal cord might offer an approach to otherwise intractable spinal root injuries. The dorsal roots of the 4th, 5th, and 6th lumbar spinal nerves of adult rats were severed and reanastomosed. Fourteen to nineteen days later, adenoviral vectors containing either the LacZ or NT-3 genes were injected into the ventral horn of the lumbar spinal cord, resulting in strong expression of the transgenes in glial cells and motor neurons between 4 and 40 days after injection. When dorsal root axons were transganglionically labelled with HRP conjugated to cholera toxin subunit B, 16 to 37 days after dorsal root injury, large numbers of labelled axons could be seen to have regenerated into the cord, but only in those animals injected with vector carrying the NT-3 gene. The regenerated axons were found at the injection site, mainly in the grey matter, and had penetrated as deep as lamina V. Gene therapy with adenoviral vectors encoding a neurotrophin has therefore been shown to be capable of enhancing and directing the regeneration of a subpopulation of dorsal root axons (probably myelinated A fibres), into and through the CNS environment. J. Neurosci. Res. 54:554–562, 1998. © 1998 Wiley-Liss, Inc.     

Astrocyte-polymer implants promote regeneration of dorsal root fibers into the adult mammalian spinal cord.

To overcome obstacles to the regeneration of crushed dorsal root fibers at the dorsal root entry zone, we have employed specially designed Millipore implants coated with embryonic astrocytes to serve as a substrate for axonal growth. This strategy was successful in promoting the growth of crushed dorsal root axons into the grey matter of the adult mammalian spinal cord in a small number of animals. Fiber ingrowth into the spinal cord was closely associated with the surface of the polymer implant. In addition, unique terminal arbor malformations, not normally present, were seen in several animals. A consistent finding was the presence of a limited inflammatory response in regions immediately adjacent to the implant where axons penetrate the spinal cord. Our findings suggest that providing the dorsal root entry zone with an embryonic milieu can stimulate a limited amount of axonal regeneration into the adult mammalian spinal cord.     

Functional repair after dorsal root rhizotomy using nerve conduits and neurotrophic molecules

Functional recovery after large excision of dorsal roots is absent because of both the limited regeneration capacity of the transected root, and the inability of regenerating sensory fibers to traverse the dorsal root entry zone. In this study, bioresorbable guidance conduits were used to repair 6-mm dorsal root lesion gaps in rats, while neurotrophin-encoding adenoviruses were used to elicit regeneration into the spinal cord. Polyester conduits with or without microfilament bundles were implanted between the transected ends of lumbar dorsal roots. Four weeks later, adenoviruses encoding NGF or GFP were injected into the spinal cord along the entry zone of the damaged dorsal roots. Eight weeks after injury, nerve regeneration was observed through both types of implants, but those containing microfilaments supported more robust regeneration of calcitonin gene-related peptide (CGRP)-positive nociceptive axons. NGF overexpression induced extensive regeneration of CGRP(+) fibers into the spinal cord from implants showing nerve repair. Animals that received conduits containing microfilaments combined with spinal NGF virus injections showed the greatest recovery in nociceptive function, approaching a normal level by 7-8 weeks. This recovery was reversed by recutting the dorsal root through the centre of the conduit, demonstrating that regeneration through the implant, and not sprouting of intact spinal fibers, restored sensory function. This study demonstrates that a combination of PNS guidance conduits and CNS neurotrophin therapy can promote regeneration and restoration of sensory function after severe dorsal root injury.     

FK506 and a nonimmunosuppressant derivative reduce axonal and myelin damage in experimental autoimmune encephalomyelitis: neuroimmunophilin ligand-mediated neuroprotection in a model of multiple sclerosis

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) in which demyelination and axonal loss result in permanent neurologic disability. We examined the neuroprotective property of the immunosuppressant FK506 (tacrolimus), FK1706 (a nonimmunosuppressant FK506 derivative) and cyclosporin A (CsA) in a chronic relapsing experimental autoimmune encephalomyelitis (EAE) model of MS. Female SJL/J mice were immunized by subcutaneous (s.c.) injection with proteolipid protein 139-151 peptide in complete Freund's adjuvant. At the onset of paralysis, 12-14 days after immunization, mice received daily s.c. injections of FK506 (0.2, 1, and 5 mg/kg), FK1706 (5 mg/kg), CsA (2, 10, and 50 mg/kg), saline or vehicle (30% dimethylsulfoxide) for 30 days. FK506 (at a dose of 5 mg/kg) reduced the severity of the initial disease and suppressed relapses. FK1706 did not significantly alter the clinical course and CsA (at a dose of 50 mg/kg) lessened the severity of the initial episode of EAE but did not alter relapses. In the thoracic spinal cord, FK506 (5 mg/kg), FK1706 (5 mg/kg), and CsA (50 mg/kg) significantly (P < 0.001) reduced the extent of damage in the dorsal, lateral, and ventral white matter by a mean of up to 95, 68, and 30%, respectively. A nonimmunosuppressant dose of FK506 (0.2 mg/kg) also significantly (P < 0.001) reduced the extent of damage in the spinal cord by a mean of up to 45%. Other dosages of these compounds were ineffective. FK506 markedly protects against demyelination and axonal loss in this MS model through immunosuppression and neuroprotection.     

Regeneration into the Spinal Cord of Transected Dorsal Root Axons Is Promoted by Ensheathing Glia Transplants

The permissivity of adult olfactory bulb to the ingrowth of olfactory axons could be due to the unique properties of ensheathing glia. To test whether these glial cells could be used to promote axonal regeneration in a spontaneously nonregenerating system, we transplanted suspensions of pure ensheathing cells into a rhizotomized spinal cord segment. Ensheathing cells were purified away from other cell types by immunoaffinity, using anti-p75 nerve growth factor receptor. After laminectomy at the lower thoracic level, the spinal cord was exposed and one dorsal root (T10) was completely transected at the cord entry point. The root stump was microsurgically anastomosed to the cord and a suspension of ensheathing cells was transplanted in the spinal cord at the dorsal root entry zone. Three weeks after transplantation, numerous regenerating dorsal root axons were observed reentering the spinal cord. Ingrowth of dorsal root axons was observed using Dil and antibodies against calcitonin gene-related peptide and growth-associated protein. Primary sensory afferents invaded laminae 1, 2, and 3, grew through laminae 4 and 5, and reached the dorsal grey commissure and lamina 4 of the contralateral side. We did not observe regenerating axons within the ipsilateral ventral horn and dorsal column. Transplanted ensheathing cells reached the same laminae as axons. Neither ensheathing cells nor regenerating axons invaded those laminae they did not inervate under normal circumstances. In conclusion, the regeneration of injured dorsal root axons into the adult spinal cord was possible after ensheathing glia transplantation. The use of ensheathing cells as stimulators of axonal growth might be generalized to other central nervous system injuries.     

Developmental regulation and possible alternative cleavage of presenilin 1 in the rat retina

Injured dorsal root axons fail to regenerate into the adult spinal cord, leading to permanent sensory loss. We investigated the ability of intrathecal neurotrophin-3 (NT3) to promote axonal regeneration across the dorsal root entry zone (DREZ) and functional recovery in adult rats. Quantitative electron microscopy showed robust penetration of CNS tissue by regenerating sensory axons treated with NT3 at 1 and 2 weeks postrhizotomy. Light and electron microscopical anterograde tracing experiments showed that these axons reentered appropriate and ectopic laminae of the dorsal horn, where they formed vesicle-filled synaptic buttons. Cord dorsum potential recordings confirmed that these were functional. In behavioral studies, NT3-treated (but not untreated or vehicle-treated) rats regained proprioception. Recovery depended on NT3-mediated sensory regeneration: preventing regeneration by root excision prevented recovery. NT3 treatment allows sensory axons to overcome inhibition present at the DREZ and may thus serve to promote functional recovery following dorsal root avulsions in humans.     

Acceleration of peripheral nerve regeneration following FK506 administration

Purpose: The severe functional and sensory deficits seen following injury to peripheral nerves makes facilitation of nerve regeneration a primary goal of the reconstructive surgeon. This study examines whether daily administration of FK506 or Cyclosporin A expedites peripheral nerve regeneration following neurotmetic injury in a rat model Methods: Inbred Buffalo rats were randomized to three experimental groups. Group I rats served as untreated controls. Rats in groups II and III received daily subcutaneous CsA (5 mg/kg), and FK506 (1 mg/kg), respectively. Each animal underwent unilateral posterior tibial nerve transection with immediate epineurial reapproximation. Functional recovery of the injured limb was assessed by serial walking track analysis. Nerve regeneration was assessed histomorphometrically via light microscopy. Results: Return of hindlimb function in control animals occurred at 32 days post injury. CsA and FK506-treated transection animals recovered at 26 and 18 days post injury, respectively. Statistically significant greater fiber density and percent neural tissue were seen in FK506- treated animals compared to control animals four weeks post transection. Conclusions: This data suggest that the daily systemic administration of both CsA and FK506 accelerate the rate of functional regeneration, following neurotmetic injuries in tbc rat model. FK506's effect on nerve growth is significantly greater than that of CsA.     

Ensheathing glia transplants promote dorsal root regeneration and spinal reflex restitution after multiple lumbar rhizotomy

Previously, we have shown that transplants of olfactory bulb ensheathing cells promoted regeneration of transected dorsal roots into the spinal cord. In this study, we assessed the ability of regenerating axons to make functional connections in the cord. Dorsal roots L3 to L6 were sectioned close to their entrance into the spinal cord and reapposed after injecting a suspension of ensheathing cells into each dorsal root entry zone (Group G). Afferent regeneration into the cord and recovery of spinal reflexes were compared with animals that received no injection (Group S) or culture medium without cells (Group C). Electrophysiological tests, to measure nerve conduction and spinal reflexes (H response and withdrawal reflex) evoked by stimulation of afferents of the sciatic nerve, were performed. At 14 days after surgery, H response was found in only 1 of 7 rats of Group G, and withdrawal reflexes were absent from all animals. At 60 days, the H response reappeared in 7 of 10 rats of Group G, and 1 of 5 of each of Groups C and S. The withdrawal reflex recovered in 4 of 10 rats of Group G, but in none of Groups C and S. Immunohistochemical labeling for CALCITONIN GENE– RELATED PEPTIDE (CGRP) in rats of Group G showed immunoreactive fibers entering the dorsal horn from sectioned roots, although at lower density than in the contralateral side. In conclusion, transplanted ensheathing cells promoted central regeneration and functional reconnection of regenerating sensory afferents. Ann Neurol 1999;45:207–215     

Time course of dorsal root axon regeneration into transplants of fetal spinal cord: I. A light microscopic study.

Cut dorsal root axons regenerate into intraspinal transplants of fetal spinal cord and establish synaptic connections there. The aims of the present study were to describe the progression of dorsal root growth within the transplants and the maturation of transplant morphology and to determine whether the regenerated dorsal root axons persist within the transplants or eventually withdraw. Embryonic (E) day 14 spinal cord was grafted into the lumbar enlargement of adult Sprague-Dawley rats, and the L4 or L5 dorsal root was cut and juxtaposed to the transplants. The morphology of the transplants was examined from 1 day to over 1 year after surgery, and the regenerated dorsal roots were labeled with immunohistochemical methods to study the subset that contains calcitonin gene-related peptide (CGRP). Embryonic spinal cord transplants survived and grew within the host spinal cord in over 90% of the animals. Transplant volume increased and the morphology of the transplants matured over the first 12 weeks and then did not change for 48-60 weeks. During the first week the transplants were composed of dissociated neurons, glia, and hematogenous cells with considerable extracellular space between them. Subsequently, the grafted neurons became densely aggregated, and non-neuronal elements such as inflammatory cells and myelin debris disappeared. CGRP-immunoreactive dorsal roots began to regenerate into the transplants within 24 hours, formed dense bundles by 4 days, and were still present at 60 weeks, the longest survival period examined. Myelination of axons within transplants began at 2 weeks. Quantitative analysis showed that the area of the transplants occupied by CGRP-labeled axons and the distribution area of the labeled axons within the transplants increased until 12 weeks and persisted unchanged for over 48 weeks. These results indicate that regenerated dorsal root axons are permanently maintained within transplants of embryonic spinal cord and suggest that the transplants can contribute to the permanent restoration of damaged intraspinal neural circuits.     

Strategies for repair of the deafferented spinal cord

Deafferentation of the spinal cord by interruption of the sensory fibers in the dorsal roots highlights the problem of regeneration failure in the central nervous system. The injured dorsal root axons regenerate steadily, albeit slowly, in the peripheral compartment of the dorsal root, but abruptly cease to elongate when confronted with the interface between the peripheral and central nervous system, the dorsal root transitional zone (DRTZ). The glial cells of the CNS and their products together form this regeneration barrier. Recent years have witnessed several successful approaches to, at least in part, overcome this barrier. Particularly promising results have been obtained by (1) the replacement of adult non-regenerating dorsal root ganglion neurons with corresponding cells from embryonic or fetal donors, (2) the implantation of olfactory ensheathing cells at the DRTZ, and (3) immediate intrathecal infusion of growth factors to which dorsal root ganglion cells respond. In all these instances, growth of sensory axons into the adult spinal cord, as well as return of spinal cord connectivity, have been demonstrated. These findings suggest routes towards treatment strategies for plexus avulsion, and contribute to our understanding of possibilities to overcome regeneration failure in the spinal cord.     

FK506 treatment inhibits caspase-3 activation and promotes oligodendroglial survival following traumatic spinal cord injury

The focus of this study is to examine the ability of FK506, an immunosuppressant that inhibits calcineurin activation, to limit caspase-3 activation in oligodendroglia following spinal cord injury (SCI). To better establish a role for calcineurin and caspase-3 activation in oligodendroglia following SCI, rats received a contusion injury to the spinal cord followed by treatment with FK506 or rapamycin (another immunosuppressant with no detectable inhibitory action on calcineurin activation). Animals were then sacrificed at 8 days postinjury and spinal cord tissue was processed using immunofluorescence histochemistry to examine cellular caspase-3 activation in ventral and dorsal white matter. In all treatment groups, numerous oligodendroglia were found to express the activated form of caspase-3 in regions proximal and distal to the injury epicenter. However, our findings suggest that treatment with FK506, but not rapamycin reduces the number of oligodendroglia expressing activated caspase-3 and increases the number of surviving oligodendroglia in dorsal white matter. These results provide initial evidence that agents that reduce the actions of calcineurin and subsequent caspase-3 activation may prove beneficial in the treatment of traumatic SCI.     

Regeneration of transected dorsal root ganglion cell axons into the spinal cord in adult frogs (Xenopus laevis)

The extent of regeneration of the central axonal processes of dorsal root ganglion cells was determined using anterograde horseradish peroxidase histochemistry at 1–12 weeks after dorsal root transection in adult frogs. At 4, 8 and 12 weeks axons were found to have regenerated across the dorsal root entry zone and into the spinal cord.