脊髓损伤修复和功能重建的瓶颈问题是：再生神经元的神经突起生长无方向性，影响和下端轴突的正确对接。有研究表明牵张可定向牵引神经突起的生长方向，但其作用机制尚未阐明。神经突起的生长过程中有两种方式：向生长锥延伸和回缩，申请人认为周期性牵张可维持"伸缩平衡"、促进突起的定向生长。申请人研究表明：周期性牵张（2.5%，0.25Hz）促进细胞内Netrin-1和DCC受体表达，而DCC受体信号通路可调节神经元分化、迁移和神经突起导向生长，提示DCC受体信号通路可能是周期性牵张牵引神经导向生长的新靶点。本项目拟采用细胞和动物实验，用定位检测和反向阻断等方法，研究周期性牵张作用下：1）神经突起的生长状态和形貌变化；2) DCC受体信号通路下游分子RhoGTPase/MAPK的表达变化，探寻周期性牵张对神经突起导向生长的作用机制和关键调控分子。本项目研究将为脊髓损伤修复提供新的理论和临床指导意义。

Axonal outgrowth and pathfinding are critical for repair and rehabilitation of spinal cord injury. Cyclic strain can well guide and direct the way of neuritis during axonal growth, which will promote cells to migrate in certain direction. But, how the direction of axon guidance is determined by cyclic strain is still not understood. Axonal attraction and repulsion responses to growth cone led neuronal migration in extension and/or retraction, which balance is important for axonal development. Our recent study showed that cyclic strain activated Netrin-1/DCC signaling to promote axonal elongation. It suggested that Netrin-1/DCC signaling may be key signal pathway during axonal outgrowth by cyclic strain stimulation. Thus, axonal elongation and animal behavior after cyclic strain stimulation will be investigated in this study. In addition, some functional antagonist were used to block key signal pathway, it will demonstrate the role of RhoGTPase/MAPK signal pathway in cyclic strain-induced axonal growth. This project will explore the DCC related RhoGTPase/MAPK signaling in the nervous system development and the potential for future research directions. Therefore, DCC related RhoGTPase/MAPK pathway might play an unexpected role in regulation of cyclic strain-induced axonal growth in future.