记忆障碍是ROSC患者发生率极高的神经系统并发症。我们最新研究发现，ROSC后小胶质细胞DAM型极化受抑制，小鼠出现明显记忆障碍，而TREM2过表达可逆转以上改变；同时，miR-362 CpG甲基化率降低，miR-362-3p差异表达且与TREM2存在反向调节关系。因此我们推测：miR-362 CpG去甲基化可下调TREM2抑制小胶质细胞DAM型极化，导致ROSC后记忆障碍发生。本项目拟先通过小鼠模型及过表达/沉默TREM2验证小胶质细胞DAM型极化受抑制是ROSC后记忆障碍发生的原因；进而从细胞和动物两个层面验证miR-362 CpG去甲基化上调miR-362-3p造成TREM2表达下降是小胶质细胞DAM型极化受抑制的原因。通过以上实验阐明小胶质细胞DAM型极化在ROSC后记忆障碍形成中的重要作用及其表观遗传学调控机制，为临床ROSC后记忆障碍提供重要的实验基础和诊治策略。

Post-ROSC memory impairment associated with highly incidence is one of the most common nervous system complications in patients of cardiac arrest. Our study has demonstrated that inhibition of microglial DAM-polarization can contribute to the development of post-ROSC memory impairment and overexpression of TREM2 can reverse the symptom of memory impairment in mice. In addition, our preliminary studies in vitro further showed that reduced DNA methylation of miR-362 and up-regulated miR-362-3p complementarily pair with TREM2 mRNA appeared in BV2 cells with Oxygen and Glucose deprivation/reperfusion model. Thus, we hypothesized that the main reason for post-ROSC memory impairment is microglial DAM-polarization Inhibition induced by hypo-methylation of miR-362 down-regulating TREM2. We will use in vitro and in vivo approach with genetic tools to test the hypothesis and to determine the underlying miR-362-3p/TREM2 mechanism. The outcomes from the proposed studies would significantly contribute to our understanding the neuropathogenesis of the post-ROSC memory impairment, leading to targeted interventions of post-ROSC memory impairment in the future.