脑出血致死致残率高，如何促进脑出血后损伤修复是目前研究难点。成体脑室管膜下区内源性神经干细胞（endogenous neural stem cell, eNSC）具有参与损伤修复的能力，但修复程度受限，研究其调控机制是关键。脑组织微环境剧烈改变是调控eNSC的重要因素，脑出血后血肿分解致脑微环境中铁超载，前期我们发现铁超载可明显引起线粒体膜电位的下降和活性氧的升高，抑制eNSC的增殖和迁移，提示铁超载参与对脑出血后eNSC的调控，并提出线粒体超氧炫异常发放介导了这一作用机制。本项目拟采用活细胞动态观察、分子生物学、基因工具鼠等方法从细胞、脑片、动物模型等层次，系统研究脑出血后铁超载对eNSC的调控作用及机制，揭示“脑出血-铁超载-超氧炫-Rho GTPase-eNSC”信号通路在其中的作用。通过本研究不仅加深人们对eNSC调控机制的认识，而且为研发促eNSC参与损伤修复的策略奠定基础。

Intracerebral hemorrhage (ICH) remains a leading cause of death and disability. Endogenous neural stem cells (eNSC) located in the adult subventricular zone will be activated by ICH to repair the injury. However, the repair ability of eNSC is limited. Thus studying the mechanisms whereby ICH modulates eNSC is important. Violent change in the niche is a vital factor modulating eNSC. Iron overload from blood red cells occurs in the brain after ICH. We found that iron overload decreased the membrane potential of mitochondria and increased reactive oxygen species, thereafter suppressed the proliferation and migration of eNSC. These fingdings suggest that iron overload plays a vital role in the modulation of eNSC. We propose that superoxide flashes might be the underlying mechanism mediated the effect of iron overload on eNSc. Based on real time vedio-imaging, molecular biological approaches, knock-out mice and transgenic mice, we will investigate the role and mechanisms of iron overload in modulating eNSC induced by ICH through cultured eNSC, brain slice and ICH animal models. We will focus on the signalling pathway in which iron overload from ICH hematoma triggers abnormal superoxide flashes to activate Rho GTPase to modulate eNSC activation. This study will not only help to bring insights into the mechanisms of eNSC modulation, but also to develop new therapeutic strategy to promote eNSC to repair brain injury.