神经干细胞(NSCs)增殖、分化是脑损伤后神经再生的重要方式。研究证实nNOS不仅可调节NSCs增殖，同时在脑损伤中起着重要的作用。我们前期发现神经元缺血损伤后磷酸化nNOS（p-nNOS）入核与Sox2相互作用，并调节Shh/Gli1信号通路中Shh的转录；同时在NSCs中我们发现了nNOS/Sox2共定位于胞核，且NSCs损伤后胞核中nNOS以磷酸化状态为主，且p-nNOS与Sox2存在相互作用。由此我们设想脑损伤后NSCs中nNOS磷酸化，p-nNOS/Sox2相互作用并通过调控Shh/Gli1通路来影响NSCs。本课题拟研究脑缺血损伤后NSCs中nNOS磷酸化水平变化；p-nNOS/Sox2相互作用及对Sox2磷酸化的影响；并进而观察p-Sox2通过调控Shh/Gli1通路对损伤后NSCs的影响，从而为脑损伤通过干预NSCs中p-nNOS/Sox2实现神经再生提供理论和实验依据。

The proliferation and differentiation of neural stem cells (NSCs) is an important way for neural regeneration after cerebral injury. Previous research has found that nNOS can regulate NSCs proliferation and plays an important role during cerebral injury. Our earlier experiment results firstly showed that phosphorylated nNOS (p-nNOS) could enter the nucleus of neuron and form interact with Sox2, then regulate the transcription of Shh after the cerebral ischemia injury. Meanwhile we also found that p-nNOS and Sox2 expressed in the nucleus of NSCs, and p-nNOS interacted with Sox2. Based on these findings above, we hypothesize that the NSCs proliferation and differentiation after cerebral injury may relate to p-nNOS/Sox2 interaction. However, the mechanism of p-nNOS/Sox2 interaction and the relationship between the p-nNOS/Sox2 and Shh/Gli1 signal pathway are still unclear. In this subject, we will firstly investigate the expression and subcellular localization of p-nNOS and its interaction with Sox2 after cerebral ischemia injury, analysis the effect on the phosphorylation of Sox2 as well as the transcription activity of Sox2, and then elucidate the possibility of the changes of NSCs through Shh/Gli1 signal pathway regulated by p-nNOS/Sox2. Finally we will intervene the interaction of p-nNOS-Sox2 to study the neuroprotective role of the p-nNOS/Sox2 during cerebral ischemia injury. This research will clarify the mechanisms of NSCs regulation by p-nNOS/Sox2 interaction and provide both the theoretical and experimental bases to explore the protective mechanisms of NSCs after cerebral ischemia.