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Introduction: The purpose of this study was to provide a comprehensive understanding of gene expression during Wallerian degeneration and axon regeneration after peripheral nerve injury. Methods: A microarray was used to detect gene expression in the distal nerve 0, 3, 7, and 14 days after sciatic nerve crush. Bioinformatic analysis was used to predict function of the differentially expressed mRNAs. Microarray results and the key pathways were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: Differentially expressed mRNAs at different time-points (3, 7, and 14 days) after injury were identified and compared with a control group (0 day). Nine general trends of changes in gene expression were identified. Key signal pathways and 9 biological processes closely associated with nerve regeneration were identified and verified. Conclusions: Differentially expressed genes and biological processes and pathways associated with axonal regeneration may elucidate the molecular-biological mechanisms underlying peripheral nerve regeneration. Muscle Nerve 55: 373–383, 2017

Objective: Transplantation of fetal spinal cord cells (FSCC) can promote regeneration of injured spinal cord, while Schwann cells (SC) and some growth factors have a similar effect. However, the synergistic effects and optimal combination of these modalities have not yet been evaluated. In the current study, the efficiency of cell therapy of FSCC and/or SC, with/without growth factors (nerve growth factor [NGF] and brain-derived neurotrophic factor [BDNF]) was examined, with the aim of establishing an optimized protocol for spinal cord injury. Methods: One hundred and twenty adult rats were randomly divided into six groups with 20 rats in each group. One week after the thoracic spinal cord injury model had been created, the rats were treated with different therapeutic modalities: Dulbecco's modified Eagles medium (DMEM) in Group I, FSCC in Group II, FSCC plus SC in Group III, FSCC plus SC over-expressing NGF in Group IV, FSCC plus SC over-expressing BDNF in Group V, and FSCC plus SC over-expressing both NGF and BDNF in Group VI. Subsequently, the rats were subjected to behavioral tests once a week after injury, while histology, immunohistochemistry and electron microscopy were performed at one and three month post-operation. Results: Both SC and FSCC promoted regeneration of spinal cord injury when used separately, while a combination of the two types of cell resulted in better recovery than either alone. Both growth factors (NGF and BDNF) enhanced the outcomes of cell therapy, while synergistic effects meant that a combination of each individual component (group VI) achieved the best results according to locomotion scale, histology and immunoreactivity in the injured cords. Conclusion: SC, NGF and BDNF can enhance the outcome of FSCC therapy, while the combination of FSC with SC, NGF and BDNF is possibly the optimal protocol for clinical treatment of acute spinal cord injury.