Glycosaminoglycan-promoted muscle reinnervation and insulin-like growth factor-I levels are affected by anti-growth hormone-releasing hormone exposure.

The present study shows that exposure to antibodies to growth hormone-releasing hormone (GHRH) partially counteracted the promoting effects of treatment with glycosaminoglycans (GAGs) on muscle reinnervation. Sciatic nerve crush was performed in 2-day-old rats, and reinnervation of the extensor digitorum longus muscle was monitored. The extent of reinnervation was rather poor in saline-treated rats, whereas in GAG-treated rats the extent of muscle reinnervation, the recovery of nerve-evoked muscle twitch tension, and the number of motor neurons reinnervating the extensor digitorum longus muscle were greatly enhanced. In addition, treatment with glycosaminoglycans increased markedly insulin-like growth factor-I (IGF-I) levels in denervated muscles. Both types of stimulatory action exerted by GAGs were affected by concomitant exposure to anti-GHRH, with abolition of IGF-I muscle increase and a smaller enhancement in muscle reinnervation.     

A morphological study of the collateral reinnervation of the cat''s canine tooth

We examined the morphologic characteristics of the collateral reinnervation of the cat's canine tooth pulp. Collateral reinnervation was stimulated in six adult cats by transecting the ipsilateral inferior alveolar nerve and preventing it from regenerating by sealing the ligated nerve inside a nylon tube. The apices of the canine teeth were examined after 15 weeks using electron microscopy and each axon was counted and measured. Compared with contralateral control teeth, the collateral reinnervation consisted of fewer myelinated fibers and in five animals the number of nonmyelinated fibers was also smaller. In one animal the nonmyelinated count on the operated side exceeded that on the control side. The total number of axons was 33.5% of the number in control teeth, considerably fewer than seen after reinnervation by regenerating fibers in previous experiments. The structural characteristics of the collateral fibers were similar to those of regenerating nerve fibers. Compared with controls the myelinated collateral fibers were smaller and had thinner myelin sheaths. There were more nonmyelinated fibers containing only one axon. More nonmyelinated fibers had exposure of part of their axolemma to the extracellular space and there was also an increase in axoaxonal apposition.     

Morphometric effects of vincristine on nerve regeneration in the rat

Administration of vincristine (200, 100 or 50 micrograms/kg/week) for 6 months during regeneration of the sciatic nerve after crush injury caused a dose-dependent reduction in nerve fibre size and failure of removal of myelin debris. Successfully regenerating neurites showed an unusual amount of shape distortion. The ratio of myelin sheath thickness to axon circumference was reduced, but the ratio of myelin sheath thickness to axon area was normal. Microtubule concentration was diminished in axons, but neurofilament density was unaffected. Unmyelinated axons were reduced in number but their axon diameter distribution was not affected. Fibres on the non-crushed side appeared normal. The toxicity of vincristine to regenerating nerves is probably related to increased blood-nerve permeability occurring both at the site of crush and along the degenerating nerve.     

Long-term consequences of impaired regeneration on facial motoneurons in the C57BL/Ola mouse

Peripheral nerves of the C57BL/Ola mouse mutant undergo markedly slowed Wallerian degeneration following injury. This is associated with impaired regeneration of both sensory and motor axons. Following a crush lesion of the facial nerve, there was no cell loss in facial nuclei of normal (C57BL/6J) adult mice, but 40% cell loss occurred in Ola mice and the survivors increased in size during the period when functional reinnervation was established. These results are interpreted as a result, first, of prolonged deprivation of target-derived trophic factor in the slowly regenerating Ola motoneurons and second, increased peripheral field size of the survivors. Within the regenerated facial nerve, there was marked heterogeneity of myelinated fibre size in Ola mice. Some Ola axons, both proximal and distal to the lesion site, had areas over twice as great as the largest 6J axons when measured 1 year following injury. A population of small diameter fibres, not observed in 6J nerves, persisted distal to the crush site in Ola nerves, and this was associated with an increase in the total number of myelinated axons in the distal nerve: on average, each parent Ola axon retained three persistent daughter axons. The delayed Wallerian degeneration in Ola mice not only impairs immediate axon regrowth, but also results in a breakdown of the normal mechanisms which regulate axon number and size in regenerating nerve.     

Misdirection of regenerating axons and functional recovery following sciatic nerve injury in rats

Poor functional recovery found after peripheral nerve injury has been attributed to the misdirection of regenerating axons to reinnervate functionally inappropriate muscles. We applied brief electrical stimulation (ES) to the common fibular (CF) but not the tibial (Tib) nerve just prior to transection and repair of the entire rat sciatic nerve, to attempt to influence the misdirection of its regenerating axons. The specificity with which regenerating axons reinnervated appropriate targets was evaluated physiologically using compound muscle action potentials (M responses) evoked from stimulation of the two nerve branches above the injury site. Functional recovery was assayed using the timing of electromyography (EMG) activity recorded from the tibialis anterior (TA) and soleus (Sol) muscles during treadmill locomotion and kinematic analysis of hindlimb locomotor movements. Selective ES of the CF nerve resulted in restored M-responses at earlier times than in unstimulated controls in both TA and Sol muscles. Stimulated CF axons reinnervated inappropriate targets to a greater extent than unstimulated Tib axons. During locomotion, functional antagonist muscles, TA and Sol, were coactivated both in stimulated rats and in unstimulated but injured rats. Hindlimb kinematics in stimulated rats were comparable to untreated rats, but significantly different from intact controls. Selective ES promotes enhanced axon regeneration but does so with decreased fidelity of muscle reinnervation. Functional recovery is neither improved nor degraded, suggesting that compensatory changes in the outputs of the spinal circuits driving locomotion may occur irrespective of the extent of misdirection of regenerating axons in the periphery.     

Enhanced reinnervation after neurotization with Schwann cell transplantation

We investigated the feasibility of using Schwann cell transplantation to enhance reinnervation after direct nerve-to-muscle neurotization (NMN). The denervated anterior tibial muscle was neurotized by tibial nerve implantation, and Schwann cell suspension (transplantation group) or an equivalent volume of culture medium (control group) was injected at the implantation site. In the control group, few axons invaded the muscle, demonstrating that skeletal muscle was poorly permissive to the advancement of axons. In the transplantation group, a large number of regenerating axons grew for a longer distance throughout the muscle, and reinnervated motor endplates were significantly more abundant. Enhanced reinnervation and functional recovery of the muscle in the transplantation group was confirmed by a significant increase in the compound muscle action potential and in muscle weight. These results suggest that intramuscular Schwann cell transplantation has potential as a cell therapy to improve functional recovery after NMN.     

Sensory axon targeting is increased by NGF gene therapy within the lesioned adult femoral nerve

Even though peripheral nerves regenerate well, axons are often misrouted and reinnervate inappropriate distal pathways post-injury. Misrouting most likely occurs at branch points where regenerating axons make choices. Here, we show that the accuracy of sensory axon reinnervation is enhanced by overexpression of the guidance molecule nerve growth factor (NGF) distal to the bifurcation. We used the femoral nerve as a model, which contains both sensory and motor axons that intermingle in the parent trunk and distally segregate into the saphenous (SB) and motor branches (MB). Transection of the parent trunk resulted in misrouting of axon reinnervation to SB and MB. To enhance sensory axon targeting, recombinant adenovirus encoding NGF was injected along the SB close to the bifurcation 1 week post-injury. The accuracy of axon reinnervation was assessed by retrograde tracing at 3 or 8 weeks after nerve injury. NGF overexpression significantly increased the accuracy of SB axon reinnervation to the appropriate nerve branch, in a manner independent of enhancing axon regeneration. This novel finding provides in vivo evidence that gradient expression of neurotrophin can be used to enhance targeting of distal peripheral pathways to increase axon regeneration into the appropriate nerve branch.     

Glycosaminoglycans co-administration enhance insulin-like growth factor-I neuroprotective and neuroregenerative activity in traumatic and genetic models of motor neuron disease: a review.

In this report it is shown how glycosaminoglycans and insulin-like growth factor-I (IGF-I) promote muscle reinnervation and prevent motor neuron death in experimental models of motor neuron disease. Such effect appears to be mediated by insulin-like growth factor-1. The glycosaminoglycan moiety of proteoglycans is a constituent of the basal lamina active on nerve regeneration by means of the interaction with laminin and with several growth factors. We have previously shown that supplementation by means of subcutaneous injections of glycosaminoglycans affects neuronal degeneration and regeneration. In this study we report that following neonatal lesion of the rat sciatic nerve, glycosaminoglycan treatment promoted extensor digitorum longus muscle reinnervation with consequent improvement of muscle morphology. In saline-treated rats, reinnervation was only partial and there was a marked muscle fibre atrophy, whereas, glycosaminoglycan treatment of lesioned rats increased IGF-I mRNA and protein in the reinnervated muscle, and IGF-I and insulin-like growth factor binding protein-3 plasma levels. Similarly, treatment of lesioned rats with IGF-I promoted muscle reinnervation, and prevented muscle fibre atrophy, higher levels of IGF-I in the reinnervated muscle, of IGF-I, and insulin-like growth factor binding proteins in plasma. In the wobbler mouse IGF-I and glycosaminoglycans alone promote only a partial motor neuron survival and the preservation of forelimb function decays after 3 weeks of treatment. However when glycosaminoglycans and insulin-like growth factor are administered together the motor neuron disease in the wobbler mouse is halted and there is no more loss of motor neurons.     

End-to-end and end-to-side neurorrhaphy between thick donor nerves and thin recipient nerves:an axon regeneration study in a rat model

During nerve reconstruction,nerves of different thicknesses are often sutured together using end-to-side neurorrhaphy and end-to-end neurorrhaphy techniques.In this study,the effect of the type of neurorrhaphy on the number and diameter of regenerated axon fibers was studied in a rat facial nerve repair model.An inflow-type end-to-side and end-to-end neurorrhaphy model with nerve stumps of different thicknesses(2:1 diameter ratio) was created in the facial nerve of 14 adult male Sprague-Dawley rats.After 6 and 12 weeks,nerve regeneration was evaluated in the rats using the following outcomes:total number of myelinated axons,average minor axis diameter of the myelinated axons in the central and peripheral sections,and axon regeneration rate.End-to-end neurorrhaphy resulted in a significantly greater number of regenerated myelinated axons and rate of regeneration after 6 weeks than end-to-side neurorrhaphy;however,no such differences were observed at 12 weeks.While the regenerated axons were thicker at 12 weeks than at 6 weeks,no significant differences in axon fiber thickness were detected between end-to-end and end-toside neurorrhaphy.Thus,end-to-end neurorrhaphy resulted in greater numbers of regenerated axons and increased axon regeneration rate during the early postoperative period.As rapid reinnervation is one of the most important factors influencing the restoration of target muscle function,we conclude that end-to-end neurorrhaphy is desirable when suturing thick nerves to thin nerves.     

Heat shock protein is a key therapeutic target for nerve repair in autoimmune peripheral neuropathy and severe peripheral nerve injury

Guillain-Barré syndrome (GBS) is an autoimmune peripheral neuropathy and a common cause of neuromuscular paralysis. Preceding infection induces the production of anti-ganglioside (GD) antibodies attacking its own peripheral nerves. In severe proximal peripheral nerve injuries that require long-distance axon regeneration, motor functional recovery is virtually nonexistent. Damaged axons fail to regrow and reinnervate target muscles. In mice, regenerating axons must reach the target muscle within 35 days (critical period) to reform functional neuromuscular junctions and regain motor function. Successful functional recovery depends on the rate of axon regeneration and debris removal (Wallerian degeneration) after nerve injury. The innate-immune response of the peripheral nervous system to nerve injury such as timing and magnitude of cytokine production is crucial for Wallerian degeneration. In the current study, forced expression of human heat shock protein (hHsp) 27 completely reversed anti-GD-induced inhibitory effects on nerve repair assessed by animal behavioral assays, electrophysiology and histology studies, and the beneficial effect was validated in a second mouse line of hHsp27. The protective effect of hHsp27 on prolonged muscle denervation was examined by performing repeated sciatic nerve crushes to delay regenerating axons from reaching distal muscle from 37 days up to 55 days. Strikingly, hHsp27 was able to extend the critical period of motor functional recovery for up to 55 days and preserve the integrity of axons and mitochondria in distal nerves. Cytokine array analysis demonstrated that a number of key cytokines which are heavily involved in the early phase of innate-immune response of Wallerian degeneration, were found to be upregulated in the sciatic nerve lysates of hHsp27 Tg mice at 1 day postinjury. However, persistent hyperinflammatory mediator changes were found after chronic denervation in sciatic nerves of littermate mice, but remained unchanged in hHsp27 Tg mice. Taken together, the current study provides insight into the development of therapeutic strategies to enhance muscle receptiveness (reinnervation) by accelerating axon regeneration and Wallerian degeneration.     

IDPN impairs post-traumatic regeneration of rat sciatic nerve

The role played by cytoskeletal proteins in nerve regeneration was investigated in a model in which the axonal transport of neurofilaments (NF) is almost selectively impaired. The administration of β, β-iminodipropionitrile (IDPN), a synthetic lathyrogenic compound, induces an axonopathy characterized by proximal axonal enlargements, due to NF accumulation, and by diffuse atrophic changes associated with spatial segregation of NF from microtubules (MT). We investigated post-axotomy regeneration of rat sciatic nerve following IDPN administration. Changes induced by IDPN, as examined in the proximal and distal nerve stump at 15 and 30 days after lesion, consisted of a statistically significant reduction of the mean axonal diameter ( P < 0.0001) as compared to control rats. In addition, the number of regenerating myelinated fibres was smaller in dosed rats ( P < 0.001) 15 days after crush, whereas at the later stage the number of axons approached that of control animals. Electrophysiological investigation revealed a delay in target reinnervation in dosed rats. Regenerating IDPN axons, both 15 and 30 days after crush contained fewer NF ( P < 0.001), while the number of MT was slightly increased as compared to controls. Taken together, our results suggest that severe alteration of NF transport, coupled with mild alteration of other components of cytoskeletal proteins, impairs the longitudinal and radial growth of regenerating myelinated axons and confirm that the number of NF is the major determinant of the cross-sectional area of each segment of the axon.     

The effect of hyperbaric oxygen treatment on early regeneration of sensory axons after nerve crush in the rat

Abstract The effect of hyperbaric oxygen treatment (HBO) on sensory axon regeneration was examined in the rat. The sciatic nerve was crushed in both legs. In addition, the distal stump of the sural nerve on one side was made acellular and its blood perfusion was compromised by freezing and thawing. Two experimental groups received hyperbaric exposures (2.5 ATA) to either compressed air (pO2 = 0.5 ATA) or 100% oxygen (pO2 = 2.5 ATA) 90 minutes per day for 6 days. Sensory axon regeneration in the sural nerve was thereafter assessed by the nerve pinch test and immunohistochemical reaction to neurofilament. HBO treatment increased the distances reached by the fastest regenerating sensory axons by about 15% in the distal nerve segments with preserved and with compromised blood perfusion. There was no significant difference between the rats treated with different oxygen tensions. The total number of regenerated axons in the distal sural nerve segments after a simple crush injury was not affected, whereas in the nerve segments with compromised blood perfusion treated by the higher pO2, the axon number was about 30% lower than that in the control group. It is concluded that the beneficial effect of HBO on sensory axon regeneration is not dose-dependent between 0.5 and 2.5 ATA pO2. Although the exposure to 2.5 ATA of pO2 moderately enhanced early regeneration of the fastest sensory axons, it decreased the number of regenerating axons in the injured nerves with compromised blood perfusion of the distal nerve stump.     

Accuracy of reinnervation by peripheral nerve axons regenerating across a 10-mm gap within an impermeable chamber.

The axon regeneration following a peripheral nerve injury often fails to restore a complete functional recovery. One of the causes of this unsatisfactory result has been attributed to regrowth of regenerating fibers to inappropriate peripheral targets. The accuracy of reinnervation by axons regenerating across a 10-mm gap within an impermeable chamber has been studied by using a sequential retrograde double-labeling technique. Despite the long gap between the nerve stumps, at 4 weeks a mean of 30.5% of the regenerating axons can reinnervate the original muscular area. These data confirm previous studies in which a preferential reinnervation is reported not to be absolutely dependent on the axon's mechanical alignment.     

Influence of terminal nerve branch size on motor neuron regeneration accuracy

A necessary prerequisite for recovery of motor function following a peripheral nerve injury is the correct choice by regenerating motor neurons to reinnervate the original distal nerve branch to denervated muscle. The present studies use the mouse femoral nerve as a model system to examine factors that influence such motor neuron regeneration accuracy. We examined motor reinnervation accuracy over time in this model under two conditions: 1) when the two terminal nerve branches to either skin (cutaneous) or muscle (quadriceps) were roughly comparable in size, and 2) when the cutaneous branch was larger than the muscle branch. When the terminal nerve branches were similar in size, motor neurons initially projected equally into both branches, but over time favored the terminal muscle branch. When the cutaneous terminal nerve branch was enlarged (via transgenic technology), motor neuron projections significantly favored this inappropriate pathway during early time points of regeneration. These results suggest that regenerating motor neuron projections are not determined by inherent molecular differences between distal terminal nerve branches themselves. Rather, we propose a two-step process that shapes motor neuron reinnervation accuracy. Initial outgrowth choices made by motor axons at the transection site are proportional to the relative amount of target nerve associated with distal nerve axons that previously projected to each of the terminal nerve pathways. Secondly, the likelihood of an axon collateral from a motor neuron remaining in either terminal nerve branch is based upon the relative trophic support provided to the parent motor neuron by the competing terminal pathways and/or end-organs.     

The increase in B-50/GAP-43 in regenerating rat sciatic nerve occurs predominantly in unmyelinated axon shafts: A quantitative ultrastructural study

The growth-associated protein B-50/GAP-43 is thought to play a crucial role in axonal growth. We investigated, by quantitative immunoelectron microscopy, whether there are differences in the subcellular distribution of B-50 in unmyelinated and myelinated axons of intact and regenerating sciatic nerves. Adult rats received an unilateral sciatic nerve crush and were euthanized 8 days later. Nerve pieces proximal from the crush site were embedded, and B-50 was visualized by specific B-50 antibodies and immunogold detection in ultrathin sections. The density of B-50 at the plasma membrane of unmyelinated axon shafts was significantly increased in the ipsilateral regenerating nerve in comparison to that of the contralateral intact nerve. In contrast, there was no significant difference in the B-50 density at the axolemma of myelinated regenerating and intact axon shafts. In the contralateral intact nerve, more B-50 was associated with the axolemma of unmyelinated axons than with the plasma membrane of myelinated axons. The density of axoplasmic B-50 was similar in intact unmyelinated and myelinated axon shafts, but was higher in regenerating nerve than in intact nerve. This suggests that enhanced axonal transport of B-50 occurs during axon outgrowth. Our study demonstrates a differential subcellular distribution of B-50 in unmyelinated and myelinated axon shafts in both the intact and regenerating sciatic nerve, indicating a differential inducible capacity for remodeling of the axon shafts. © 1995 Wiley-Liss, Inc.     

Manipulations of the mouse femoral nerve influence the accuracy of pathway reinnervation by motor neurons

Previous studies using the femoral nerve model in both mice and rats have shown that regenerating motor axons prefer to reinnervate the terminal nerve branch to muscle versus a terminal nerve branch to skin, a process that has been termed preferential motor reinnervation (PMR). If end organ contact with muscle and skin is prevented, this preferential motor reinnervation still occurs in the rat. To better understand the process of preferential motor reinnervation in the mouse, we examined motor neuron reinnervation of muscle and cutaneous pathways without any end organ contact as well as with only cutaneous end organ contact. Surprisingly, there was no preferential motor reinnervation: Motor neurons preferred the cutaneous pathway over the muscle pathway when all end organ contact was prevented and showed an even greater preference for the cutaneous pathway when it was attached to skin.     

Reinnervation of spinal cord anterior horn cells after median nerve repair using transposition with other nerves

Our previous studies have confirmed that during nerve transposition repair to injured peripheral nerves, the regenerated nerve fibers of motor neurons in the anterior horn of the spinal cord can effectively repair distal nerve and target muscle tissue and restore muscle motor function. To observe the effect of nerve regeneration and motor function recovery after several types of nerve transposition for median nerve defect(2 mm), 30 Sprague-Dawley rats were randomly divided into sham operation group, epineurial neurorrhaphy group, musculocutaneous nerve transposition group, medial pectoral nerve transposition group, and radial nerve muscular branch transposition group. Three months after nerve repair, the wrist flexion test was used to evaluate the recovery of wrist flexion after regeneration of median nerve in the affected limbs of rats. The number of myelinated nerve fibers, the thickness of myelin sheath, the diameter of axons and the cross-sectional area of axons in the proximal and distal segments of the repaired nerves were measured by osmic acid staining. The ratio of newly produced distal myelinated nerve fibers to the number of proximal myelinated nerve fibers was calculated. Wet weights of the flexor digitorum superficialis muscles were measured. Muscle fiber morphology was detected using hematoxylin-eosin staining. The cross-sectional area of muscle fibers was calculated to assess the recovery of muscles. Results showed that wrist flexion function was restored, and the nerve grew into the distal effector in all three nerve transposition groups and the epineurial neurorrhaphy group. There were differences in the number of myelinated nerve fibers in each group. The magnification of proximal to distal nerves was 1.80, 3.00, 2.50, and 3.12 in epineurial neurorrhaphy group, musculocutaneous nerve transposition group, medial pectoral nerve transposition group, and radial nerve muscular branch transposition group, respectively. Nevertheless, axon diameters of new nerve fibers, cross-sectional areas of axons, thicknesses of myelin sheath, wet weights of flexor digitorum superficialis muscle and cross-sectional areas of muscle fibers of all three groups of donor nerves from different anterior horn motor neurons after nerve transposition were similar to those in the epineurial neurorrhaphy group. Our findings indicate that donor nerve translocation from different anterior horn motor neurons can effectively repair the target organs innervated by the median nerve. The corresponding spinal anterior horn motor neurons obtain functional reinnervation and achieve some degree of motor function in the affected limbs.     

Regeneration and soma size changes following axotomy of the trochlear nerve

The effects of CNS and PNS axotomy of the IVth nerve on cell death, soma size, axon size, and axon number were investigated. In adult cats, the IVth nerve was axotomised by using four surgical paradigms: (1) peripheral IVth nerve crush, (2) peripheral IVth nerve cut, (3) peripheral IVth nerve resection, and (4) a CNS IVth nerve cut in the velum. The extent of cell death resulting from each surgical paradigm was determined. Following axotomy distal to the decussation of the IVth nerves, cell death was least after nerve crush, intermediate after nerve cut, and maximal after resection of 5-7 mm of the nerve. Following axotomy at the decussation--a CNS lesion--most cells died but some successful regeneration was observed. Soma size measurements following a short-term survival (3 days to 4 weeks) before the regenerating axons reached their target muscle revealed that somas of axotomised cells underwent hypotrophy within 1 week of axotomy and then gradually increased in size. They re-attained normal size by 4 weeks postoperative when regenerating axons first reach their target. Following a long-term survival (greater than 2 months), somas were significantly hypertrophied, and the degree of hypertrophy was inversely related to the extent of cell survival up to a limit of 40% soma size increase. Counts and measurements of axons revealed that mean axon diameter of regenerated axons was much smaller than normal 3 months after axotomy, increased during the third to sixth postoperative months, but then showed no subsequent increase and remained below normal. In animals with cell death varying from 10% to 70%, the number of axons in the nerve was maintained constant at approximately 1,000. These data indicate that there is a mechanism for the production and maintenance of the appropriate number of regenerative axonal branches following axotomy. In animals in which cell death exceeded 70%, the number of axons was controlled by a maximum ratio of 3 to 4 axon branches per surviving cell. The results suggest that axon number is strongly influenced by the target muscle and that hypertrophy of regenerated cells is related to the number of axonal sprouts each cell has to produce and support in order to re-establish the preoperative number of axons in the regenerated trochlear nerve.     

Biodegradable magnesium wire promotes regeneration of compressed sciatic nerves

Magnesium(Mg) wire has been shown to be biodegradable and have anti-inflammatory properties. It can induce Schwann cells to secrete nerve growth factor and promote the regeneration of nerve axons after central nervous system injury. We hypothesized that biodegradable Mg wire may enhance compressed peripheral nerve regeneration. A rat acute sciatic nerve compression model was made, and AZ31 Mg wire(3 mm diameter; 8 mm length) bridged at both ends of the nerve. Our results demonstrate that sciatic functional index, nerve growth factor, p75 neurotrophin receptor, and tyrosine receptor kinase A m RNA expression are increased by Mg wire in Mg model. The numbers of cross section nerve fibers and regenerating axons were also increased. Sciatic nerve function was improved and the myelinated axon number was increased in injured sciatic nerve following Mg treatment. Immunofluorescence histopathology showed that there were increased vigorous axonal regeneration and myelin sheath coverage in injured sciatic nerve after Mg treatment. Our findings confirm that biodegradable Mg wire can promote the regeneration of acute compressed sciatic nerves.