Ganglioside promotes the bridging of sciatic nerve defects in cryopreserved peripheral nerve allografts

Previous studies have shown that exogenous gangliosides promote nervous system regeneration and synapse formation.In this study,10 mm sciatic nerve segments from New Zealand rabbits were thawed from cryopreservation and were used for the repair of left sciatic nerve defects through allograft bridging.Three days later,1 m L ganglioside solution(1 g/L) was subcutaneously injected into the right hind leg of rabbits.Compared with non-injected rats,muscle wet weight ratio was increased at 2–12 weeks after modeling.The quantity of myelinated fibers in regenerated sciatic nerve,myelin thickness and fiber diameter were elevated at 4–12 weeks after modeling.Sciatic nerve potential amplitude and conduction velocity were raised at 8 and 12 weeks,while conduction latencies were decreased at 12 weeks.Experimental findings indicate that ganglioside can promote the regeneration of sciatic nerve defects after repair with cryopreserved peripheral nerve allografts.     

miR-30c promotes Schwann cell remyelination following peripheral nerve injury

Differential expression of miRNAs occurs in injured proximal nerve stumps and includes miRNAs that are firstly down-regulated and then gradually up-regulated following nerve injury. These miRNAs might be related to a Schwann cell phenotypic switch. miR-30c, as a member of this group, was further investigated in the current study. Sprague-Dawley rats underwent sciatic nerve transection and proximal nerve stumps were collected at 1, 4, 7, 14, 21, and 28 days post injury for analysis. Following sciatic nerve injury, miR-30c was down-regulated, reaching a minimum on day 4, and was then upregulated to normal levels. Schwann cells were isolated from neonatal rat sciatic nerve stumps, then transfected with miR-30c agomir and co-cultured in vitro with dorsal root ganglia. The enhanced expression of miR-30c robustly increased the amount of myelin-associated protein in the co-cultured dorsal root ganglia and Schwann cells. We then modeled sciatic nerve crush injury in vivo in Sprague-Dawley rats and tested the effect of perineural injection of miR-30c agomir on myelin sheath regeneration. Fourteen days after surgery, sciatic nerve stumps were harvested and subjected to immunohistochemistry, western blot analysis, and transmission electron microscopy. The direct injection of miR-30c stimulated the formation of myelin sheath, thus contributing to peripheral nerve regeneration. Overall, our findings indicate that miR-30c can promote Schwann cell myelination fol-lowing peripheral nerve injury. The functional study of miR-30c will benefit the discovery of new therapeutic targets and the development of new treatment strategies for peripheral nerve regeneration.     

Edaravone promotes functional recovery after mechanical peripheral nerve injury

Edaravone has been shown to reduce ischemia/reperfusion-induced peripheral nerve injury. However, the therapeutic effect of edaravone on peripheral nerve injury caused by mechanical factors is unknown. In the present study, we established a peripheral nerve injury model by crushing the sciatic nerve using hemostatic forceps, and then administered edaravone 3 mg/kg intraperitoneally. The sciatic functional index and superoxide dismutase activity of the sciatic nerve were increased, and the malondialdehyde level was decreased in animals in the edaravone group compared with those in the model group. Bcl-2 expression was increased, but Bax expression was decreased in anterior horn cells of the L4–6 spinal cord segments. These results indicated that edaravone has a neuroprotective effect following peripheral nerve injury caused by mechanical factors through alleviating free radical damage to cells and inhibiting lipid peroxidation, as well as regulating apoptosis-related protein expression.     

Scaffoldless tissue-engineered nerve conduit promotes peripheral nerve regeneration and functional recovery after tibial nerve injury in rats

Damage to peripheral nerve tissue may cause loss of function in both the nerve and the targeted muscles it innervates. This study compared the repair capability of engineered nerve conduit (ENC), engineered fibroblast conduit (EFC), and autograft in a 10-mm tibial nerve gap. ENCs were fabricated utilizing primary fibroblasts and the nerve cells of rats on embryonic day 15 (E15). EFCs were fabricated utilizing primary fi-broblasts only. Following a 12-week recovery, nerve repair was assessed by measuring contractile properties in the medial gastrocnemius muscle, distal motor nerve conduction velocity in the lateral gastrocnemius, and histology of muscle and nerve. The autografts, ENCs and EFCs reestablished 96%, 87% and 84% of native distal motor nerve conduction velocity in the lateral gastrocnemius, 100%, 44% and 44% of native specific force of medical gastrocnemius, and 63%, 61% and 67% of native medial gastrocnemius mass, re-spectively. Histology of the repaired nerve revealed large axons in the autograft, larger but fewer axons in the ENC repair, and many smaller axons in the EFC repair. Muscle histology revealed similar muscle fiber cross-sectional areas among autograft, ENC and EFC repairs. In conclusion, both ENCs and EFCs promot-ed nerve regeneration in a 10-mm tibial nerve gap repair, suggesting that the E15 rat nerve cells may not be necessary for nerve regeneration, and EFC alone can suffice for peripheral nerve injury repair.     

Immediate versus delayed primary nerve repair in the rabbit sciatic nerve

It is well known that peripheral nerve injury should be treated immediately in the clinic, but in some instances, repair can be delayed. This study investigated the effects of immediate versus delayed （3 days after injury） neurorrhaphy on repair of transected sciatic nerve in New Zealand rabbits using stereological, histomorphological and biomechanical methods. At 8 weeks after immediate and delayed neurorrhaphy, axon number and area in the sciatic nerve, myelin sheath and epineurium thickness, Schwann cell morphology, and the mechanical property of nerve fibers did not differ obviously. These results indicate that delayed neurorrhaphy do not produce any deleterious effect on sciatic nerve repair.     

Immune reactions and nerve repair in mice with sciatic nerve injury 14 days after intraperitoneal injection of Brazil

BALB/c mice were intraperitoneally injected with 10, 5 or 2.5 mg/kg Brazil for 14 days after sciatic nerve injury. Results demonstrate that the spleen T/B lymphocyte stimulation index and serum circulating immune complex concentration were significantly reduced, and the morphology of the soleus muscle was restored in mice with sciatic nerve injury. These effects of Brazil were dose-dependent. Our experimental findings indicate that Brazil can regulate immune responses after nerve injury and promote sciatic nerve repair.     

Use of nerve conduits for peripheral nerve injury repair A Web of Science-based literature analysis

OBJECTIVE: To identify global research trends in the use of nerve conduits for peripheral nerve injury repair. DATA RETRIEVAL: Numerous basic and clinical studies on nerve conduits for peripheral nerve injury repair were performed between 2002-2011. We performed a bibliometric analysis of the institutions, authors, and hot topics in the field, from the Web of Science, using the key words peripheral nerve and conduit or tube. SELECTION CRITERIA: Inclusion criteria: peer-reviewed published articles on nerve conduits for peripheral nerve injury repair, indexed in the Web of Science; original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. Exclusion criteria: articles requiring manual searching or telephone access; documents not published in the public domain; and several corrected papers. MAIN OUTCOME MEASURES: (a) Annual publication output; (b) publication type; (c) publication by research field; (d) publication by journal; (e) publication by funding agency; (f) publication by author; (g) publication by country and institution; (h) publications by institution in China; (i) most-cited papers. RESULTS: A total of 793 publications on the use of nerve conduits for peripheral nerve injury repair were retrieved from the Web of Science between 2002-2011. The number of publications gradually increased over the 10-year study period. Articles constituted the main type of publication. The most prolific journals were Biomaterials, Microsurgery, and Journal of Biomedical Materials Research Part A. The National Natural Science Foundation of China supported 27 papers, more than any other funding agency. Of the 793 publications, almost half came from American and Chinese authors and institutions. CONCLUSION: Nerve conduits have been studied extensively for peripheral nerve regeneration; however, many problems remain in this field, which are difficult for researchers to reach a consensus.     

Phototherapy for enhancing peripheral nerve repair: a review of the literature

Posttraumatic nerve repair continues to be a major challenge of restorative medicine. Although enormous progress has been made in surgical techniques over the past three decades, functional recovery after a severe lesion of a major nerve trunk is often incomplete and sometimes unsatisfactory. It is thus particularly important to investigate clinical protocols to enhance nerve regeneration after surgical nerve repair. The present article reviews literature on one possible rehabilitation approach for enhancing nerve recovery, namely phototherapy. The number of experimental studies that have reported on the promoting action of phototherapy on peripheral nerve regeneration, together with the few known side effects related to the use of this type of physical therapy, make it possible to suggest that the time for broader clinical trials has come.     

Calcitonin pump improves nerve regeneration after transection injury and repair

Introduction: After nerve injury, excessive calcium impedes nerve regeneration. We previously showed that calcitonin improved nerve regeneration in crush injury. We aimed to validate the direct effect of calcitonin on transected and repaired nerve. Methods: Two rat groups (n = 8) underwent sciatic nerve transection followed by direct repair. In the calcitonin group, a calcitonin‐filled mini‐osmotic pump was implanted subcutaneously, with a catheter parallel to the repaired nerve. The control group underwent repair only, without a pump. Evaluation and comparison between the groups included: (1) compound muscle action potential recording of the extensor digitorum longus (EDL) muscle; (2) tetanic muscle force test of EDL; (3) nerve calcium concentration; and (4) nerve fiber count and calcified spot count. Results: The calcitonin pump group showed superior recovery. Conclusions: Calcitonin affects injured and repaired peripheral nerve directly. The calcitonin‐filled mini‐osmotic pump improved nerve functional recovery by accelerating calcium absorption from the repaired nerve. This finding has potential clinical applications. Muscle Nerve 51 : 229–234, 2015     

The Achyranthes bidentata polypeptide k fraction enhances neuronal growth in vitro and promotes peripheral nerve regeneration after crush injury in vivo

We have previously shown that Achyranthes bidentata polypeptides （ABPP）, isolated from Achyranthes bidentata Blume （a medicinal herb）, exhibit neurotrophic and neuroprotective effects on the nervous system. To identify the major active component of ABPP, and thus optimize the use of ABPP, we used reverse-phase high performance liquid chromatography to separate ABPP. We obtained 12 fractions, among which the fraction of ABPPk demonstrated the strongest neuroactivity. Immunocytochemistry and western blot analysis showed that ABPPk promoted neurite growth in cultured dorsal root ganglion explant and dorsal root ganglion neurons, which might be associated with activation of Erk1/2. A combination of behavioral tests, electrophysiological assessment, and histomorphometric analysis indicated that ABPPk enhanced nerve regeneration and function restoration in a mouse model of crushed sciatic nerve. All the results suggest that ABPPk, as the key component of ABPP, can be used for peripheral nerve repair to yield better outcomes than ABPP.     

Omental graft improves functional recovery of transected peripheral nerve

The omentum has several properties that are advantageous for neuronal sprouting and direction. We have therefore analyzed functional recovery following transection of rat sciatic nerve using omental graft to bridge the nerve defect. In group 1, a 25-30-mm nerve defect was produced and bridged with omental graft, whereas in group 2, an end-to-end repair was performed. The sciatic function index (SFI) was assessed at 2-week intervals until 8 weeks after surgery. Functional recovery was faster in group 1 than in group 2. After 8 weeks, SFI was improved significantly from -100% to -45% (+/- -4%) in group 1 (P < 0.001) compared to -72% +/- -2% in group 2 (n = 10). Histologically, the omental graft contained more newly developed nerve fibers and less scar tissue than the end-to-end repair. Thus, omental graft appears to improve directional growth of regenerating axon sprouts and may be a means of treating peripheral nerve injury.     

Changes in nerve microcirculation following peripheral nerve compression

Following peripheral nerve compression, peripheral nerve microcirculation plays important roles in regulating the nerve microenvironment and neurotrophic substances, supplying blood and oxygen and maintaining neural conduction and axonal transport. This paper has retrospectively analyzed the articles published in the past 10 years that addressed the relationship between peripheral nerve compression and changes in intraneural microcirculation. In addition, we describe changes in different peripheral nerves, with the aim of providing help for further studies in peripheral nerve microcirculation and understanding its protective mechanism, and exploring new clinical methods for treating peripheral nerve compression from the perspective of neural microcirculation.     

Chemically extracted aceUular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair

A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune rejection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regeneration. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group 〉 chemically extracted acellular nerve graft ＋ ciliary neurotrophic factor group 〉 chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anastomosis, but superior to chemically extracted acellular allogeneic nerve bridging alone.     

Factors predicting sensory and motor recovery after the repair of upper limb peripheral nerve injuries

OBJECTIVE： To investigate the factors associated with sensory and motor recovery after the repair of upper limb peripheral nerve injuries. DATA SOURCES： The online PubMed database was searched for English articles describing outcomes after the repair of median, ulnar, radial, and digital nerve injuries in humans with a publication date between 1 January 1990 and 16 February 2011. STUDY SELECTION： The following types of article were selected： （1） clinical trials describ- ing the repair of median, ulnar, radial, and digital nerve injuries published in English; and （2） studies that reported sufficient patient information, including age, mechanism of injury, nerve injured, injury location, defect length, repair time, repair method, and repair materials. SPSS 13.0 software was used to perform univariate and multivariate logistic regression analyses and to in- vestigate the patient and intervention factors associated with outcomes. MAIN OUTCOME MEASURES： Sensory function was assessed using the Mackinnon-Dellon scale and motor function was assessed using the manual muscle test. Satisfactory motor recovery was defined as grade M4 or M5, and satisfactory sensory recovery was defined as grade S3＋ or S4. RESULTS： Seventy-one articles were included in this study. Univariate and multivariate logistic regression analyses showed that repair time, repair materials, and nerve injured were inde- pendent predictors of outcome after the repair of nerve injuries （P 〈 0.05）, and that the nerve injured was the main factor affecting the rate of good to excellent recovery. CONCLUSION： Predictors of outcome after the repair of peripheral nerve injuries include age, gender, repair time, repair materials, nerve injured, defect length, and duration of follow-up.     

Vitamin B complex and vitamin B12 levels after peripheral nerve injury

The aim of the present study was to evaluate whether tissue levels of vitamin B complex and vitamin B12 were altered after crush-induced peripheral nerve injury in an experimental rat model. A total of 80 male Wistar rats were randomized into one control (n = 8) and six study groups (1, 6, 12, 24 hours, 3, and 7 days after experimental nerve injury;n = 12 for each group). Crush-induced peripheral nerve injury was per-formed on the sciatic nerves of rats in six study groups. Tissue samples from the sites of peripheral nerve injury were obtained at 1, 6, 12, 24 hours, 3 and 7 days after experimental nerve injury. Enzyme-linked immunosorbent assay results showed that tissue levels of vitamin B complex and vitamin B12 in the injured sciatic nerve were signiifcantly greater at 1 and 12 hours after experimental nerve injury, while they were signiifcantly lower at 7 days than in control group. Tissue level of vitamin B12 in the injured sciatic nerve was signiifcantly lower at 1, 6, 12 and 24 hours than in the control group. These results suggest that tissue levels of vitamin B complex and vitamin B12 vary with progression of crush-induced peripheral nerve injury, and supplementation of these vitamins in the acute period may be beneficial for acceleration of nerve regeneration.     

Dexamethasone prevents vascular damage in early-stage non-freezing cold injury of the sciatic nerve

Non-freezing cold injury is a prevalent cause of peripheral nerve damage, but its pathogenic mechanism is poorly understood, and treatment remains inadequate. Glucocorticoids have anti-inflammatory and lipid peroxidation-inhibiting properties. We therefore examined whether dexamethasone, a synthetic glucocorticoid compound, would alleviate early-stage non-freezing cold injury of the sciatic nerve. We established Wistar rat models of non-freezing cold injury by exposing the left sciatic nerve to cold(3–5°C) for 2 hours, then administered dexamethasone(3 mg/kg intraperitoneally) to half of the models. One day after injury, the concentration of Evans blue tracer in the injured sciatic nerve of rats that received dexamethasone was notably lower than that in the injured sciatic nerve of rats that did not receive dexamethasone; neither Evans blue dye nor capillary stenosis was observed in the endoneurium, but myelinated nerve fibers were markedly degenerated in the injured sciatic nerve of animals that received dexamethasone. After dexamethasone administration, however, endoneurial vasculopathy was markedly improved, although damage to the myelinated nerve fiber was not alleviated. These findings suggest that dexamethasone protects the blood-nerve barrier, but its benefit in non-freezing cold injury is limited to the vascular system.     

Tacrolimus reduces scar formation and promotes sciatic nerve regeneration

A sciatic nerve transection and repair model was established in Sprague-Dawley rats by transecting the tendon of obturator internus muscle in the greater sciatic foramen and suturing with nylon sutures. The models were treated with tacrolimus gavage (4 mg/kg per day) for 0, 2, 4 and 6 weeks. Specimens were harvested at 6 weeks of intragastric administration. Masson staining revealed that the collagen fiber content and scar area in the nerve anastomosis of the sciatic nerve injury rats were significantly reduced after tacrolimus administration. Hematoxylin-eosin staining showed that tacrolimus significantly increased myelinated nerve fiber density, average axon diameter and myelin sheath thickness. Intragastric administration of tacrolimus also led to a significant increase in the recovery rate of gastrocnemius muscle wet weight and the sciatic functional index after sciatic nerve injury. The above indices were most significantly improved at 6 weeks after of tacrolimus gavage. The myelinated nerve fiber density in the nerve anastomosis and the sciatic nerve functions had a significant negative correlation with the scar area, as detected by Spearman’s rank correlation analysis. These findings indicate that tacrolimus can promote peripheral nerve regeneration and accelerate the recovery of neurological function through the reduction of scar formation.     

修复周围神经损伤的神经移植材料

摘要：周围神经大段损伤一直是康复领域的重大难题,所以修复损伤的周围神经逐渐成为热点话题。在众多的修复方法中,移植修复周围神经损伤已经成为研究热点。自体移植物是临床上的“黄金标准”,人工组织工程材料移植物来源广泛,同种异体移植物可避免异体移植造成的免疫排斥反应。文章采用文献收集及总结的方法,探讨了自体移植物,人工组织工程材料移植物和同种异体移植物的研究进展。 关键词：周围神经;损伤;再生;移植;综述文献     

Surgical repair of peripheral nerve injury

Magnification, use of fine interfascicular grafts for repair, and development of intraoperative electrophysiologic measurements of function have had a substantial impact on this field in the last 10 to 20 years. Basic surgical principles established during and since World War II remain the foundation for surgical repair of peripheral nerve injury but have been complemented nicely by these more recent advances. Selection of patients for surgery, as well as the timing of such, has been reviewed with emphasis on the differences between suspected transections and lesions in continuity, as well as comments on serious peripheral entrapments and tumors affecting nerve. The importance of not only preoperative electromyographic studies but also the intraoperative use of stimulation and stimulation and recording of nerve action potentials (NAPs) for lesions in continuity has been stressed. Operative techniques such as neurolysis, NAP recordings, suture, split repair, and interfascicular graft repair have been reviewed and some commentary on results provided. There has been a gradual evolution of centers in this country and abroad for care of the more serious surgical nerve problems. It is anticipated that in the future, such centers will be able to provide improved data concerning results with civilian nerve injuries.     

施万细胞在修复外周神经损伤中作用机制的研究进展

外周神经损伤后若不能及时准确的修复,则会导致外周神经功能的永久丧失。目前研究显示施万细胞(SC)参与外周神经损伤后碎片清除、轴突和髓鞘再生以及靶器官再支配过程中,外周神经损伤后SC被迅速激活进入修复过程,经历一系列动态的细胞重塑变化,转化为修复表型,促进神经再生、引导对靶器官再支配,从而恢复神经功能,其中有许多信号通路,转录调节因子等调控这些过程。基于此,该文系统总结了SC在外周神经再生过程中的研究进展,为深入研究外周神经修复提供新的方法和策略。