神经重塑可改善脑缺血后的功能预后。研究表明MSCs源性exosome较MSCs同样有神经重塑的作用，且起效更快更安全。MSCs源性exosome引起脑缺血后的神经重塑，主要表现为轴突再生，可能与TNF-α相关。但具体的调控通路不明。而TNF-α主要受proNGF-p75NTR的调控。肺癌相关研究提示细胞凋亡与exosome介导proNGF-p75NTR相关，但在脑缺血中调控通路尚不明确。申请人前期工作发现，脑缺血后proNGF的表达上调，且与p75NTR结合，调控细胞凋亡。此外还发现proNGF-p75NTR受huwe1的严格调控，并参与了脑缺血后的神经重塑过程。因此我们推测，MSCs源性exosome介导的脑缺血后的神经重塑过程，可能是通过huwe1调控proNGF-p75NTR通路进行。本研究拟采用分子生物学及核磁共振结合的方式，探讨MSCs源性exosome在脑缺血后神经重塑的机制。

Neurological remodeling after cerebral ischemia can improve the functional prognosis. Many studies have shown that exosome derived from mesenchymal stem cells(MSCs) has the effect of neural remodeling. Moreover, it is safer and more effective than MSCs itself. The MSCs-exosome can induce nerve remodeling after cerebral ischemia though the axon regeneration, which may be related to TNF-α. But the specific regulatory pathway is not clear. TNF-α is mainly regulated through the pathway of proNGF-p75NTR axis. The studies in lung cancer suggested that exosome induce apoptosis through the proNGF-p75NTR/sortilin axis, but the role of exosome in the cerebral ischemia is unclear. Besides, we found that the expression of proNGF was up-regulated in mice after cerebral ischemia and proNGF can regulate cell apoptosis by combining with p75NTR. Furthermore, we found that the axis of proNGF-p75NTR is regulated by huwe1 strictly and participates in the process of nerve remodeling after cerebral ischemia. Therefore, we hypothesis that the effect of neural remodeling mediated by MSCs exosome which associate with huwe1 regulate proNGF-p75NTR after cerebral ischemia. In this study, molecular biology and MRI were used to investigate the mechanism of exosome in neural remodeling after cerebral ischemia.