神经干细胞在脑卒中后的神经康复中具有良好的治疗潜力，提高其增殖与分化能力有望显著增加其疗效。研究表明，Wnt/beta-catenin信号通路对神经干细胞增殖与分化有重要调节作用，但其激动剂R-spondin (Rspo)蛋白对神经干细胞的作用尚无报道。我们前期研究发现，Rspo在小鼠SVZ与SGZ脑区有较高水平的表达；在体外实验中Rspo可协同Wnt蛋白显著促进小鼠神经干细胞的增殖与分化。本项目将1）确定Rspo是否能协同Wnt蛋白激活神经干细胞中Wnt/beta-catenin信号通路；2）探索Rspo对小鼠脑卒中后神经干细胞增殖与分化、神经与运动功能的作用；3）初步阐明Rspo协同Wnt蛋白调控神经干细胞增殖与分化的分子机制。本项目将揭示Rspo蛋白对神经干细胞增殖与分化的调控作用与机制，为开发新的促进脑卒中后神经康复的生物大分子药物提供实验依据。

Neural stem cells (NSCs) are one of the promising candidates for the treatment of post-stroke neurorehabilitation, and the improvement of its proliferation and differentiation ability is expected to enhance its therapeutic benefit significantly. Studies have shown that the Wnt/beta-catenin signaling pathway plays an important role in regulating the proliferation and differentiation of neural stem cells, but the role of the agonist r-spondin (Rspo) protein on neural stem cells has not been reported. Our previous studies have found that Rspo proteins have high levels of expression in SVZ and SGZ in mice; Rspo can significantly promote the proliferation and differentiation of neural stem cells in vitro. This project will determine 1) whether Rspo can coordinate with Wnt proteins to activate the Wnt/beta-catenin signaling pathway in neural stem cells; 2) Explore the role of Rspo in the proliferation and differentiation of neural stem cells and the neural/ motor function after stroke; 3) Preliminarily elucidate the molecular mechanism of synergia by Rspo and Wnt proteins on regulating the proliferation and differentiation of neural stem cells. This project will reveal the regulation effect and mechanism of Rspo protein on neural stem cell proliferation and differentiation and provide experimental basis for the development of new biological macromolecular drugs to promote post-stroke neurorehabilitation.