动员内源性干细胞促进脊髓损伤环路调控的神经修复机制研究

脊髓损伤是致残率极高的疾患，尚无确切有效治疗。近期发现脊髓中央管周围内源性神经干细胞的存在，提示动员内源性神经干细胞，促进突触形成和环路重建，是脊髓损伤修复的重大科学问题。本团队对趋化因子CXCL12有丰厚的研究基础，且创新改良神经环路磁刺激技术NC-MS和STDP，在脊髓损伤患者取得初步疗效。 团队将开创性地建立NC-MS和STDP脊髓损伤动物模型, 支撑神经调控的机制研究。本课题将聚焦研究CXCL12对损伤区内源性神经干细胞的动员、突触形成以及协同神经调控促进环路重建的作用，旨在阐明CXCL12通过外泌体导向促进神经修复的机制，研究具有理论创新性；本课题也将揭示CXCL12对内源性干细胞的动员作用，建立促进突触形成的干预路径，具有潜在的技术创新性；利用动物模型深入探索NC-MS和STDP神经调控的修复机制，为神经调控协同CXCL12促进脊髓损伤修复提供科学证据，并具有潜在的临床价值。

Spinal cord injury is a traumatic disorder with high disability rate, and there is no definite and effective treatment. Recently, the existence of endogenous neural stem cells around the central canal of the spinal cord has been found, which suggests that how to mobilize endogenous neural stem cells and promote stem cell differentiation, synapse formation and neural circuit reconstruction is a major scientific issue in the repair of spinal cord injury. The research group of this project has strong research foundation on chemokine CXCL12, and innovated TMS－derived NC-MS and STDP that have achieved preliminary clinical efficacy in patients with spinal cord injury. The groundbreaking establishment of NC-MS and STDP animal models in spinal cord injury will play an important role in research of neuromodulation. In this study, we will focus on the role of CXCL12 in mobilization, synaptogenesis and synergistic regulation with neural circuit modulation in spinal cord injury. To elucidate the mechanism of sustained release CXCL12 promoting nerve repair by directing exosomes has clear theoretical innovation; This study will reveals the role of CXCL12 in mobilizing stem cells in microenvironment, establishes a technical system to improve intercellular communication and promote synapse formation in microenvironment, which has potential technological innovation; And takes the lead in exploring NC-MS and STDP nerves in animal models. The mechanism of neuromodulation provides scientific evidence for the synergistic effect of neuromodulation and CXCL12 on the nerve repair of spinal cord injury. It has potential clinical application value.