脊髓损伤后的抑制性微环境制约了神经再生，其中脑源性神经营养因子前体proBDNF是造成抑制性微环境的重要因素。基于富含proBDNF受体的雪旺细胞外泌体可以有效修复受损神经的新发现，结合课题组前期对雪旺细胞调节脊髓损伤微环境的研究，本课题将探索通过雪旺细胞外泌体修复脊髓损伤的新方法，并提出雪旺细胞外泌体通过拮抗proBDNF改善微环境、修复脊髓损伤的机制假说。为阐明雪旺细胞外泌体对脊髓损伤抑制性微环境的调控机制，本课题拟从雪旺细胞外泌体组分的蛋白质组和转录组分析入手，找出外泌体的成分与修复作用的对应关系；体外实验观察其对proBDNF抑制修复所需神经元、巨噬细胞和星型胶质细胞的调控作用；体内实验观察雪旺细胞外泌体修复大鼠脊髓损伤及对proBDNF的抑制作用的影响。雪旺细胞外泌体应用于脊髓损伤修复将有望突破抑制性微环境的修复瓶颈。本研究将为脊髓损伤提供新的修复手段及理论基础。

Inhibitory microenvironment after spinal cord injury has restricted the nerve regeneration. The precursor of brain derived neurotrophic factor, proBDNF, is one of the most important factors causing inhibitory microenvironment. Based on latest discovery that Schwann cell-derived exosomes contain rich proBDNF receptors which can effectively repair the damaged nerve, and our early findings that Schwann cell can adjust the spinal cord injury microenvironment, this study will explore new methods of repair of spinal cord injury by Schwann cell-derived exosomes, and put forward the hypothesis that Schwann cell-derived exosomes can improve and repair spinal cord injury through antagonism with proBDNF. To clarify the regulatory mechanism of Schwann cell-derived exosomes to inhibitory microenvironment caused by spinal cord injury, the study will explore the ingredients of Schwann cell-derived exosomes through proteome and transcriptome analysis to find out the corresponding relationship between the composition of exosomes and the function of the repair. The regulatory effect of Schwann cell-derived exosomes to neuron, macrophage and astrocyte through suppression of proBDNF will be explored in vitro. In vivo experiment, the impact of Schwann cell-derived exosomes on spinal cord injury in rats and inhibiting action on proBDNF will be explored. The research of Schwann cell-derived exosomes in repair of spinal cord injury is expected to break through the bottleneck of inhibitory microenvironment post spinal cord injury. This study will provide new repair methods and theoretical basis for spinal cord injury.