脑缺血诱发神经元凋亡，但其调节的分子机制尚不完全清楚。本课题前期首次发现脑缺血再灌注诱导与CaMKⅡ亚型CaMK2D有序列重叠的lncRNA-C2dat2在缺血再灌注后缺血半影区表达上调。沉默C2dat2降低CaMKⅡ磷酸化，抑制p38诱导的神经元凋亡。已知CaMKⅡ磷酸化是神经元损伤的重要机制之一。因此我们提出假说：脑缺血再灌注通过诱导C2dat2的表达促进CaMKⅡ磷酸化进而激活p38信号通路而诱导神经元凋亡。本课题拟在前期研究基础上：1.通过体外细胞和体内动物实验验证脑缺血再灌注通过诱导C2dat2的表达，激活CaMKⅡ-p38信号通路而促进神经元凋亡；2.阐明脑缺血后C2dat2调控神经元凋亡的分子机制。本研究可以丰富lncRNA的生物学功能，在lncRNA水平揭示脑缺血再灌注神经元凋亡的分子机制，为寻找脑卒中治疗靶点提供新思路。

The mechanism of neuronal apoptosis after cerebral ischemia is not clear yet. Our previous study reveal that lncRNA C2dat2 overlap with the CaMK2D gene sequence which is the subtype of CaMKII, upregulated trend during cerebral ischemia reperfusion. The phosphorylation of CaMKII is decreased and p38 induced neuronal apoptosis is inhibited by silencing C2dat2. To our knowledge，transient cerebral ischemia and reperfusion can increase the level of CaMKII phosphorylation, and the phosphorylation of CaMKII is one of the important mechanisms for neuronal damage. Therefore, we hypothesis that long non-coding RNA C2dat2 promotes CaMKII phosphorylation to induced neuronal apoptosis through the p38 signaling pathway following cerebral ischemia. On the base of our preliminary studies，this project will further intend to verify that C2dat2 promotes CaMKII phosphorylation to induced neuronal apoptosis through the p38 signaling pathway following cerebral ischemia in vitro and in vivo. and then investigate the regulatory mechanism of C2dat2 to induce neuronal apoptosis following cerebral ischemia. This project will enrich the biological function of lncRNAs and the mechanism of neuronal apoptosis after cerebral ischemia in the lncRNAs level, and may provide a new target and new idea to benefit the prognosis and treatment of ischemic stroke.