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Traumatic brain injury(TBI)is a multifaceted disease with a complex pathogenesis for which there are currently no effective therapeutic interventions.Research has shown that bone marrow mesenchymal stem cell-derived extracellular vesicles(BMSC-EVs)may play a therapeutic role in TBI.They attenuate neuroinflammatory responses at the site of the lesion and promote neurovascular regeneration.However,the exact mechanisms underlying their actions are not fully understood.This article aims to review the current state of research on the therapeutic mechanisms of BMSC-EVs in TBI.It also aims to discuss possible future research directions and potential clinical applications of BMSC-EVs.
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Traumatic brain injury (TBI) is one of the diseases with high morbidity,mortality,and disability,which seriously endangers human health.Primary and secondary injuries caused by TBI are cascade reaction of various pathophysiological interactions.Because of its many injury factors and complex mechanisms,the treatment and therapeutic effect of TBI are limited at present.In recent years,animal experiments and clinical studies have shown that stem cell therapy could alleviate TBI-mediated neurological damage to a certain extent.Therefore,activation of endogenous neural cells response and transplantation of exogenous stem cells may be new strategies for TBI treatment.This article reviews the research progress of activation of endogenous neural cells response and transplantation of exogenous stem cells after TBI,and focuses on the therapeutic effects and possible mechanisms of stem cell transplantation in TBI treatment.
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Objective To explore the effect of biphasic electrical stimulation (BES) on the proliferation and differentiation of rats olfactory bulb neural precursor cells (OB NPCs).Methods OB NPCs of one day old neonatal rats were isolated,cultured,passaged and identified.They were randomly divided into a control group and an electrical stimulation (ES) group.The OB NPCs in the ES group were exposed to BES with a 50 mV/mm or 100 mV/mm electric field for 24 hours with a pulse width of 8 ms,while the control group was not given electrical stimulation.The immunofluorescent technique and 3(4,5 dimethythiazol-2-y1)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric assay were used to assess the cells' proliferation and differentiation.Results The cell viability and the number of glial fibrillary acidic protein positive cellsin the ES group were significantly higher than in the control group.Conclusions BES may be used as an auxiliary technique for improving cell survival and differentiation in stem cell-based transplantation therapy as it can promote proliferation and differentiation,at least of OB NPCs.
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Objective To explore the protective effects of Quercetin on hypoxic ischemic brain damage (HIBD). Methods Forty-eight 7-day-old SD rats were randomly divided into sham-operation group, HIBD group and Que treatment group, 16 rats each. HIBD group and Que treatment group were treated by ligation of right common carotid artery to make anoxia and build HIBD model; sham-operation group had the separation of the right common carotid artery only. Que treatment group were injected intraperitoneally with quercetin (40 mg/kg) once a day for 7 days immediately after modeling while sham-operation group and HIBD group received equivalent normal saline at the same time. The rats in each group were scored of neurological function at 1 h after the last administration, and the ability of spatial learning-memory was tested by Morris water maze at the age of 28 days. After performing the test above, all rats were decapitated and the brains were taken. Pathological changes of hippocampus were observed by HE staining; the expression of brain-derived neurotrophic factor (BDNF) and nerve growth associated protein (GAP-43) in hippocampus CA1 area were detected by immunohistochemistry. Results There were significant differences in neurological deficit score and learning-memory ability among the three groups (P<0.01), and neurological deficit score was the highest and the learning-memory ability was the lowest in HIBD group. Pathological examination showed that the structure of hippocampal neurons was intact in sham-operation group. It was loose and disorder, and even loss of neurons in HIBD group. Compared with the HIBD group, the loose in the structure of hippocampal was lighter, and the number of neurons was increased in the Que treatment group. There was statistical difference in the positive expression of BDNF and GAP-43 in the hippocampal CA1 area among the three groups (P<0.01), with those in HIBD group being lower than in Que treatment group and sham-operation group and those in treatment group being lower than in sham-operation group (P<0.01). Conclusions Quercetin can enhance the expression of BDNF and GAP-43 in hippocampal CA1 region, promote nerve regeneration, improve the long-term learning-memory ability of HIBD neonatal rats, and protect the brain.
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@#Objective To investigate the effect of Santong electroacupuncture (EA) on mRNA and protein expression of p75 neurotroph-in receptor (p75NTR) in rats with spinal cord injury (SCI). Methods A total of 72 female Sprague-Dawley rats were randomly assigned to sham operation group (group A, n=8) and model group (n=64). In the model group, Allen's method was used to make SCI rats model, in which 48 survived model rats were further subdivided into model control group (group B, n=12), EA group (group C, n=12), inhibitor Nogo extra cellular peptide residues 1-40 (NEP1-40) group (group D, n=12) and EA+inhibitor NEP1-40 group (group E, n=12) according to de-sign proposal. The treatment groups were electroacupunctured on Dazhui (GV14) and Yaoyangguan (GV3), bilateral Ciliao (BL32) and Zu-sanli (ST36) with loose-tight wave, for 20 minutes every day. After 7 and 14 days of treatment, injured spinal cord tissue was extracted for detecting. The mRNA and protein expression of p75NTR was detected by real-time fluorescent quantitative PCR, in situ hybridization and Western blotting respectively. The hind limb motor function was assessed with Basso-Beattie-Bresnahan (BBB) score. Results The BBB score increased in the treatment groups compared with group B, and was higher in group E than in groups C and D (P<0.05), as well as on the 14th day than on the 7th day in all the treatment groups (t>2.623, P<0.05). The mRNA and protein expression of p75NTR in spinal cord tissues decreased in the treatment groups compared with group B (P<0.05), and no significant difference was found among the treatment groups (P>0.05). Conclusion Santong elerctroacupuncture treatment could improve the hind limb motor function, which may associate with inhibition of the mRNA and protein expression of p75NTR in rats after SCI.
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The neural stem cells (NSCs) can migrate into the injured area and differentiate into neurons or oligodendrocytes.Endogenous neurogenesis may potentially be harnessed as a putative therapy for neural injury.But the complex micro-environment due to TBI will be one of the biggest challenges for endogenous NSCs to perform neural regenerations.Exogenous NSCs have been shown to be able to survive in host tissues and regulate microenvironment via paracrine effects.Thus, transplantation of NSCs to assist neural regeneration has become an attractive option.Recently, rapid advances in the stem cell biology have raised appealing possibilities of replacing damaged or lost neural cells by transplantation of in vitro-expanded stem cells and/or their neuronal progeny.
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Objective To investigate any effects of carbamylated erythropoietin (CEPO) on the expression of LINGO-1,growth-associated protein-43 (GAP-43) and the infarcted volume after cerebral ischemia,so as to explore the effect of CEPO on neural regeneration after cerebral ischemia.Methods Forty-eight Sprague-Dawley rats were randomly divided into a sham operation group,an ischemia control group and a CEPO treatment group,each of 16.Middle cerebral artery occlusion (MCAO) was used to simulate focal cerebral ischemia in all except the rats in the sham operation group.Then the CEPO group was injected with 0.5 ml of CEPO,while the other two groups were given a 0.5 ml injection of normal saline daily for 7 days before they were sacrificed to prepare slices of brain tissue.Western blotting was used to detect the expression of LINGO-1 and activated caspase-3.Immunohistochemical staining was applied to observe the expression of GAP-43.The slices of brain tissue were stained with cresyl violet and the volume of infarction and edema were quantified with the Image J software.Results The average expression of LINGO1 in the sham operation group,the ischemia control group and the CEPO treatment group were (0.25±0.02),(1.22±0.06) and (0.66±0.05) respectively,with significant differences among the 3 groups.There was no expression of activated caspase-3 in the sham operation group.However,the expression of activated caspase-3 increased significantly (to 86.6±10.2)% in the ischemia control group and increased significantly less (to 40.3±8.7)% in the CEPO treatment group.The average positive expression of GAP-43 in the sham operation group,the ischemia control group and the CEPO treatment group were 0,(55.02± 1.62) and (72.11±3.23)/HP,respectively,with significant differences among them.Moreover,the average volumes of cerebral infarction and brain edema in the CEPO treatment group were significantly lower than those in the ischemia control group.Conclusions CEPO can inhibit the expression of LINGO-1 and activated caspase-3,promote the expression of GAP-43,reduce infarct volume and limit cerebral edema so as to promote neural regeneration after cerebral ischemia,at least in rats.
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Objective To observe the influence of swimming training on the expression of nerve growth factor (NGF) and neurotrophins-3 (NT-3) in rats with cerebral infarction,and to explore the underlying neuroprotection mechanism of exercise training on cerebral infarction.Methods Forty-five healthy male Sprague-Dawley rats were randomly divided into a sham-operation group,a control group and a training group,with 15 rats in each group.Each group was further divided into a 3-day,7-day and 14-day subgroups,which amounts to 9 groups.To establish animal model of cerebral ischemia-reperfusion in rats,the intraluminal thread method was applied to cause left middle cerebral artery occlusion (MCAO) for 2 h before reperfusion.The rats of the training group were given swimming training for 10 min,once daily,while those of the sham-operation and control groups were not given any training.Neurological deficits were assessed using Bederson scores.The expression of NGF mRNA and NT-3 mRNA in the ischemiareperfusion pallium was examined using reverse transcription-polymerase chain reaction (RT-PCR).Results The rats of the sham-operation group showed no neurological deficits.At the same time points,the average Bederson scores of the training group were significantly lower than the control group,but significantly higher than the sham group.Moreover,the 14 d training group had the lowest Bederson score (1.20 ±0.45),compared to the value 3 and 7 days after modeling.The expression of NGF mRNA and NT-3 mRNA of ischemic cerebral cortex in the training group was significantly improved when compared to the sham-operation group or the control group.On day 14,the expression of the NGF mRNA (0.66 ± 0.07),and the NT-3 mRNA (0.79 ± 0.06),were significantly higher than those on day 3 and 7.Conclusions Swimming training could increase the expressions of NGF mRNA and NT-3 mRNA in the ischemic cerebral cortex.It might be one of the key mechanisms that exercise training could promote the recovery of damaged neurological function in rats with cerebral infarction.
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This article presents concepts related to Rho/ROCK signal pathway, and its effect on axonal regeneration and the mechanism of its action to provide a theoretical basis for the inhibition of this signal pathway to promote neural regeneration and functional recovery and further for clinical treatment of nerve injuries and other nervous system diseases.
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Introdução: Hiperidrose é uma condição idiopática caracterizada por sudorese excessiva generalizada ou restrita a extremidades. O tratamento definitivo e com menor morbidade é a simpatectomia videotoracoscópica. O bloqueio da cadeia simpática com clipe possibilitaria a reversão da cirurgia para pacientes que sofrem de hiperidrose compensatória pós-operatória complicação mais problemática. Como objetivo, este trabalho visa analisar a arquitetura ultraestrutural e morfométrica do nervo isquiático de ratos Wistar machos adultos submetidos à compressão crônica através de um clipe cirúrgico. Os objetivos são identificar se há alteração nervosa com o clipamento e se existe tempo para promover o retorno às atividades neuronais pós-retirada do clipe. Pode-se, portanto, verificar se o clipamento é eficaz como forma de tratamento para hiperidrose, com a vantagem de ser um procedimento reversível. Métodos: Foram selecionados 30 ratos Wistar machos separados em 3 grupos 1, 2 e 3 com n=10, com a retirada do clipe em 1, 2 e 4 semanas, respectivamente. Cada grupo foi dividido em A e B com n=5. Todos os ratos do grupo A eram sacrificados no momento da retirada do clipe e, no B, uma semana após a retirada do clipe. Resultados: O estudo mostrou que, em cada um dos grupos, houve nervos normais e com degeneração, independentemente da retirada do clipe ou de sua manutenção. Conclusão: Simpatectomia com clipe parece não ser um bom método para o tratamento da hiperidrose. O efeito da simpatectomia com clipe e sua remoção devem ser melhor observados em grandes estudos (AU)
Introduction: Hyperhidrosis is an idiopathic condition characterized by excessive sweating that may be generalized or restricted to specific parts of the body. The definitive treatment with less morbidity is endoscopic thoracic sympathectomy. Blockade of the sympathetic chain with a clip enables reversal of surgery for patients suffering from postoperative compensatory sweating the most problematic complication. This work was designed to assess the ultrastructural and morphometric architecture of the sciatic nerve of adult male Wistar rats subjected to chronic compression via surgical clip. The aims were to determine if there are changes to nerve from clipping and if there is time to restore neuronal activity after removal of the clip. One can thus check if clipping is an effective treatment for hyperhidrosis, with the advantage of being a reversible procedure. Methods: Thirty male Wistar rats were selected and divided into 3 groups of ten rats each, with removal of the clip at weeks 1, 2 and 4, respectively. Each group was divided into A and B with n = 5. Rats in group A were sacrificed at the time of clip withdrawal and rats in group B were sacrifi ced one week after clip withdrawal. Results: The study showed that, in each of the groups, there were normal and degenerated nerves regardless of clip removal or maintenance. Conclusion: Sympathectomy with clip does not seem to be a good method for the treatment of hyperhidrosis. The effect of sympathectomy with clip and its removal should be further investigated in larger studies (AU)
Subject(s)
Animals , Rats , Sciatic Nerve/anatomy & histology , Nerve Crush/methods , Sympathectomy/methods , Rats, Wistar/anatomy & histology , Disease Models, Animal , Hyperhidrosis/surgery , Nerve RegenerationABSTRACT
10.3969/j.issn.2095-4344.2013.25.013
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BACKGROUND: Therapeutic methods for of peripheral facial nerve injury include surgery, physical therapy and drug treatment, but the treatment effect is not ideal in some certain cases. OBJECTIVE: To study the effect of autologous platelet rich plasma on repair of facial nerve injury. METHODS: The bilateral destroyed buccal nerve branches of the 10 white rabbits were put in silica gel nerve regeneration chamber, one side injected with platelet rich plasma as experimental group, the other side injected with normal saline as control group. The general observation, neuroelectrophysiology detection, histological observation, image analysis and evaluation of facial nerve regeneration recovery were performed at 8 weeks after surgery. RESULTS AND CONCLUSION: The action potential latency of the orbicularis oris at the experimental side was significantly lower than that at the control side, and the action potential amplitude (M wave) of compound nerve muscle of the experimental side was significantly higher than that of the control side (P < 0.01). Compared with the control side, the regenerative nerves of the experimental side were more mature with more regenerative axons, and the differentiation of myelin sheath was more mature and the thickness of myelin sheath was wel -distributed. Meanwhile, the diameters of axons were closed to the normal diameter, and the nerve axons were more intensive and arranged more regularly, the outer membrane of nerve fiber was thicker and the col agen fiber and elastic fiber layer were increased when compared with the control group. The number of regenerative axons of the control side was less, and the axons were distributed irregularly and poorly developed, and a large number of fibrous connective tissues were observed. The vacuolar degeneration at the control side was more than the experimental side. The regenerated nerve in the experimental side was better than the control side in the diameter of myelinated axon, area, myelin sheath thickness and axon count, and there were significant differences between two groups (P < 0.01). It indicates that platelet rich plasma has a promoting effect in the repair and regeneration of facial nerve.
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OBJECTIVE: To explore the effects of helicid on the hippocampal neurogenesis in chronically stressed mice and its possible action mechanism of antidepressants. METHODS: Mice were exposed to chronic stress and isolated breed for 28 consecutive days with coadministration of helicid (10, 20, 40 mg · kg-1, ig) or fluoxetine(2.6 mg · kg-1, ig). The proliferation of hippocampal progenitor cells and level of brain derived neurotrophic factor (BDNF) were measured by immunohistochemistry and Western blot analysis. RESULTS: Immunohistochemistry showed decreased expression of BrdU and BDNF in hippocampal dentate gyrus in chronic stress mice. Compared with chromic stress group, helicid and fluoxetine significantly increased expression of BrdU and BDNF. CONCLUSION: The antidepressant mechanisms of Helicid in chronically stressed mice is probalblely related to promote neurogenesis in dentate gyrus and induce up-regulation of BDNF. Copyright 2012 by the Chinese Pharmaceutical Association.
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Objective To evaluate and compare the adult neural stem cells (NSCs) derived from the subventricular zone (SVZ), adipose tissue (AD) and bone marrow (BM) in SD rat in terms of their morphologies, their potential of neural differentiation and their ability to secrete neurotrophins (NTs).Methods Tissues from the suventricular zone, adipose tissue and bone marrow in the same SD rat were chosen and induced in vitro into SVZ-NSCs, AD-NSCs and BM-NSCs, respectively. The abilities of proliferation and differentiation of these 3 NSCs were compared. Immunocytochemistry and Western blotting were employed to detect the expressions of surface markers of neurons and neuroglia, including nestin,βtubulin, galactocerebroside C (GalC) and glial fibrillary acidic protein (GFAP). The secretions of BDNF and NGF were detected by ELIS A. Results No obvious differences of morphology between SVZ-NSCs and both BM-NSCs and AD-NSCs were found (P>0.05). The proliferation ability of SVZ-NSCs was stronger than that of BM-NSCs and AD-NSCs. The percentage of nestin-positive cells in the SVZ-NSCs was significantly higher than that in the BM-NSCs or AD-NSCs (P<0.05). No obvious differences in the expressions of βtubulin, GFAP, and GalC among the 3 groups were found (P>0.05).The secretions of BDNF and NGF in all the 3 groups could be noted; those in the SVZ-NSCs was significantly higher than those in the BM-NSCs and AD-NSCs (P<0.05); those in the AD-NSCs was slightly higher than those in the BM-NSCs. Conclusions SVZ-NSCs, AD-NSCs and BM-NSCs show similar morphological and phenotypic characteristics; however, SVZ-NSCs present more powerful proliferation, differentiation and secretion abilities than AD-NSCs and BM-NSCs. Considering about such problems as immuno-repulsion, ethic and the origins, AD-NSCs appear to be the better choice than BSVZ-NSCs and M-NSCs.
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Objective To study the effects of rehabilitation training on the expression of Nogo-A around the area of cerebral infraction using rats. Methods A total of 60 Wistar rats were randomly divided into a reha- bilitation group and a control group after an experimental cerebral infarction had been established in them. The ani- mals in the rehabilitation group were given exercise with a rotating bar, a balance beam and a rolling cage for one hour daily, while those in the control group were caged without any abnormal exercise. Nogo-A expression in the ar- ea surrounding the infarcts was detected by imunohistochemical techniques at the 3rd, 7th, 14th, 21st and 28th day after infarction. Meanwhile, neurobehavioral evaluations were also conducted. Results The animals in the rehabilitation group scored much lower than the controls in the behavioral evaluations at the 14th, 21st and 28th day. The expression of Nogo-A in tissues around the infracted area increased by the 7th day and peaked at the 21st day in both groups, but the expression of Nogo-A was significantly stronger in the rehabilitation group at the 14th, 21st and 28th days. Conclusion Rehabilitation training decreased the expression of Nogo-A in the brain of rats after infarction. This may have important implications for the functional recovery of the central nervous system.
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Myelin-associated inhibitory factor is a major obstacle for axonal regeneration in the central nervous system, and Nogo-A is an important inhibiting factor synthesized by oligoden-drocytes. Toe expression levels of Nogo-A changed significantly in a model of ischemic cere-brovascular disease; the therapeutic measures aiming at Nogo-A and its downstream pathway can effectively enhance axonal regeneration, improve the plasticity of neural structure, and promote functional recovery. This provides a reliable theoretical basis for the development of therapeutic mode in human cerebrovascular diseases.
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PURPOSE: To evaluate the effect of neural stem cells differentiated from a human telencephalon on the neural regeneration in the severed spinal cord. MATERIALS AND METHODS: The 1st surgery involving the insertion of plastic membrane in the transected cord was performed to prevent spontaneous healing of adult female rats (n=20, 171-237 g) with a complete spinal cord transection. The media was inserted only after removing the previously inserted plastic membrane in the control group (n=6). In the experimental group (n=14), media and neural stem cell (1x) were transplanted after removing the membrane, and immunohistochemical staining was performed. The experimental group was perfused transcardially 5 weeks after the 2nd surgery, and the level of neural cell regeneration determined by immunohistochemical staining. In behavioral analysis, the Basso-Beatie-Bresnahan (BBB) scores of the control and experimental group were compared weekly from immediately after the injury until 5 weeks post-injury after the 2nd surgery. RESULTS: Immunohistochemical stain revealed no neural regeneration in the control group. On the other hand, the survival of transplanted human neural stem cells and remarkable neural regeneration (differentiate to neuron and astrocyte) were observed in the experimental group. In the BBB locomotor scale, the experimental group showed significant recovery in terms of control; and the score increased from postoperative 2 weeks to 3 weeks, and reached a plateau from 3 weeks to 5 weeks. CONCLUSION: The effect of neural stem cells differentiated from human telencephalon on cord regeneration does not produce functional recovery in the BBB locomotor scale, but there is slight recovery of the muscle function. The survival of transplanted human neural stem cells and the possibility of differentiation to neurons or astrocytes were observed.
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Adult , Animals , Female , Humans , Rats , Astrocytes , Hand , Membranes , Neural Stem Cells , Neurons , Plastics , Regeneration , Spinal Cord Injuries , Spinal Cord Regeneration , Spinal Cord , TelencephalonABSTRACT
@#Objective To investigate the effect of passive exercise on neural functional recovery after peripheral nerve crushed injury.MethodsThe effect of passive exercise on early peripheral nerve regeneration and recovery of motor function were observed with electrophysiological and histological indexes compared with that of the splinting group.ResultsThe nerve conduction of training group was faster than that in the splinting group,and the latency of compound muscle action potentials(CMAP)was shorter(P<0.05).The thickness of myelin sheath,average numbers of myelinated nerve fibera per area and diameter of regenerating axon in training group were larger than those in the splinting group(P<0.05).The wet weight of sural triceps of training group were bigger than that of the splinting group(P<0.01).ConclusionThe passive exercise can improve the early recovery of motor function and neural regeneration after peripheral nerve crushed injury.
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@#Schwann cells (SCs) have potently neuroprotective and myelinization abilities. They are one of the earliest and the most frequently used cells that are applied to therapeutic studies in spinal cord injury. At present, SCs are usually used as a platform for therapeutic alliance to integrate various interventions. This review will mainly discuss the issues met in therapeutic alliances with SCs for spinal cord injuries, results of various therapeutic alliances with SCs, positive effects of co-transplantation with SCs on neural stem cells, survival, migration of SCs after transplantation and roles of endogenetic SCs in repairing spinal cord injury.
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@#ObjectiveTo evaluate the effects of expanded polytetrafluoroethylene (e-PTFE) and collagen tubes in the repair of facial nerve in rabbits.MethodsThe facial nerves of rabbits were transected and removed for 5 mm. The nerve ends were then repaired with an e-PTFE or collagen tube, and with an autologous nerve graft as control. After 7 days, 1 month and 3 months, the animals' neural conductive velocity were determined. And then, the nerve specimens were taken out, and the myelinated fibers across the specimen were counted with histological examination.ResultsOn the 7th day, no neural regeneration was observed. But new forming neural fibers across the biocompatible materials and autologous nerve grafts were seen in the following 3 months, while the number and conductive velocity of myelinated fibers varied significantly at the different time points.Conclusione-PTFE and collagen conduits are effective in the repair of peripheral nerves.