Wallerian degeneration is a subject of major interest in neuroscience. A large number of genes are differentially regulated during the distinct stages of Wallerian degeneration: transcription factor activation, immune response, myelin cell differentiation and dedifferentiation. Although gene expression responses in the distal segment of the sciatic nerve after peripheral nerve injury are known, differences in gene expression between the proximal and distal segments remain unclear. In the present study in rats, we used microarrays to analyze changes in gene expression, biological processes and signaling pathways in the proximal and distal segments of sciatic nerves under-going Wallerian degeneration. More than 6,000 genes were differentially expressed and 20 types of expression tendencies were identiifed, mainly between proximal and distal segments at 7-14 days after injury. The differentially expressed genes were those involved in cell differentiation, cytokinesis, neuron differentiation, nerve development and axon regeneration. Furthermore, 11 biological processes were represented, related to responses to stimuli, cell apoptosis, inlfammato-ry response, immune response, signal transduction, protein kinase activity, and cell proliferation. Using real-time quantitative PCR, western blot analysis and immunohistochemistry, microarray data were veriifed for four genes: aquaporin-4, interleukin 1 receptor-like 1, matrix metallopro-teinase-12 and periaxin. Our study identiifes differential gene expression in the proximal and distal segments of a nerve during Wallerian degeneration, analyzes dynamic biological changes of these genes, and provides a useful platform for the detailed study of nerve injury and repair during Wallerian degeneration.

Claudin 14 has been shown to promote nerve repair and regeneration in the early stages of Wallerian degeneration (0–4 days) in rats with sciatic nerve injury, but the mechanism under-lying this process remains poorly understood. This study reported the effects of claudin 14 on nerve degeneration and regeneration during early Wallerian degeneration. Claudin 14 expression was up-regulated in sciatic nerve 4 days after Wallerian degeneration. The altered expression of claudin 14 in Schwann cells resulted in expression changes of cytokines in vitro. Expression of claudin 14 affected c-Jun, but not Akt and ERK1/2 pathways. Further studies revealed that enhanced expression of claudin 14 could promote Schwann cell proliferation and migration. Silencing of claudin 14 expression resulted in Schwann cell apoptosis and reduction in Schwann cell proliferation. Our data revealed the role of claudin 14 in early Wallerian degeneration, which may provide new insights into the molecular mechanisms of Wallerian degeneration.

This study investigated the possible involvement of microRNAs in the regulation of genes that participate in peripheral neural regeneration. A microRNA microarray analysis was conducted and 23 microRNAs were identiifed whose expression was signiifcantly changed in rat dorsal root ganglia after sciatic nerve transection. The expression of one of the downregulated microRNAs, microRNA-214, was validated using quantitative reverse transcriptase-PCR. MicroRNA-214 was predicted to target the 3′-untranslated region of Slit-Robo GTPase-activating protein 3. In situ hybridization veriifed that microRNA-214 was located in the cytoplasm of dorsal root ganglia primary neurons and was downregulated following sciatic nerve transection. Moreover, a com-bination of in situ hybridization and immunohistochemistry revealed that microRNA-214 and Slit-Robo GTPase-activating protein 3 were co-localized in dorsal root ganglion primary neu-rons. Western blot analysis suggested that Slit-Robo GTPase-activating protein 3 was upregulated in dorsal root ganglion neurons after sciatic nerve transection. These data demonstrate that mi-croRNA-214 is located and differentially expressed in dorsal root ganglion primary neurons and may participate in regulating the gene expression of Slit-Robo GTPase-activating protein 3 after sciatic nerve transection.

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 expres-sion 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 mechan-ical factors through alleviating free radical damage to cells and inhibiting lipid peroxidation, as well as regulating apoptosis-related protein expression.

The increase in neurotrophic factors after craniocerebral injury has been shown to promote fracture healing. Moreover, neurotrophic factors play a key role in the regeneration and repair of peripheral nerve. However, whether craniocerebral injury alters the repair of peripheral nerve injuries remains poorly understood. Rat injury models were established by transecting the left sciatic nerve and using a free-fall device to induce craniocerebral injury. Compared with sciat-ic nerve injury alone after 6-12 weeks, rats with combined sciatic and craniocerebral injuries showed decreased sciatic functional index, increased recovery of gastrocnemius muscle wet weight, recovery of sciatic nerve ganglia and corresponding spinal cord segment neuron mor-phologies, and increased numbers of horseradish peroxidase-labeled cells. These results indicate that craniocerebral injury promotes the repair of peripheral nerve injury.

A total of 3,446 publications regarding sciatic nerve injury repair and protection indexed by Web of Science during 2000-2004 were used for a detailed analysis of temporal-spatial distribu-tion characteristics. Reference co-citation networks of the 100 top-cited publications as per the number of total citations were created using the Web of Science database and the information visualization tool, CiteSpaceIII. The key words that showed high frequency in these publications were included for analyzing the research fronts and development trends for sciatic nerve injury repair and protection. Through word frequency trend analysis, studies on bone marrow mesen-chymal stem cells, adipose-derived stem cells, and skeletal muscle-derived multipotent stem cells combined with tissue-engineered scaffold material will become the forefronts in the ifeld of sci-atic nerve injury repair and protection in the near future.

Propofol can inhibit the inflammatory response and reduce the secretion and harmful effects of as-trocyte-derived proinflammatory cytokines. In this study, after propofol was injected into the injured sciatic nerve of mice, nuclear factor kappa B expression in the L 4-6 segments of the spinal cord in the injured side was reduced, apoptosis was decreased, nerve myelin defects were al eviated, and the nerve conduction block was lessened. The experimental findings indicate that propofol inhibits the inflammatory and immune responses, decreases the expression of nuclear factor kappa B, and reduces apoptosis. These effects of propofol promote regeneration fol owing sciatic nerve injury.