脊髓损伤（SCI）的治疗仍是一项世界性医学难题，其难点在于无法达到满意的神经再生。室管膜细胞（ECs）具有一定的神经再生修复作用，SCI后其可获得神经干细胞多向分化能力，但在体内几乎全部分化为星形胶质细胞、构成胶质瘢痕，阻碍神经元轴突生长。因此，定向诱导ECs向功能性神经元分化将可能成为脊髓损伤修复的重要途径。本项目拟采用转录因子ASCL1与营养因子BDNF联合定向诱导ECs分化，通过形态学观察、分子生物学检测分析ECs的分化及神经元的产生；通过BBB评分、CBS评分以及神经电生理改变判定脊髓神经功能的恢复。同时为进一步阐释ASCL1诱导ECs分化的可能机制，我们采用740Y-P和PTEN来调控PI3K信号通路，观察ECs的存活、增殖及分化情况，以阐明PI3K/AKT/ASCL1在ECs定向神经元分化促脊髓损伤修复中的作用机制，从而为内源性神经干细胞治疗脊髓损伤提供新的思路和理论基础。

The treatment of spinal cord injury (SCI) is still a worldwide medical problem, and the challenge is that there is no way to achieve satisfactory nerve regeneration. Ependymal cells (ECs) have a certain role in nerve regeneration and repair, and can acquire the multi-directional differentiation ability like neural stem cells after SCI, but almost all differentiate into astrocytes, constitute glial scars, and block neuronal axons growing. Therefore, the differentiation of induced ECs into functional neurons may be an important way to repair spinal cord injury. This project intends to use the transcription factor ASCL1 and trophic factor BDNF to induce ECs differentiation, and analyze the differentiation of ECs and the production of neurons by morphological observation and molecular biological detection. The BBB score, CBS score and neurophysiological changes are used to determine recovery of spinal nerve function. At the same time, in order to further elucidate the possible mechanism of ASCL1-induced ECs differentiation, 740Y-P and PTEN were used to regulate PI3K/AKT signaling pathway, and the survival, proliferation and differentiation of ECs were observed to elucidate the role and mechanism of PI3K/AKT/ASCL1 in neuron differentiation of ependymal cells to promote recovery of spinal cord injury, thus to provide new ideas and theoretical basis for the treatment of spinal cord injury by endogenous stem cells.