Tregs在SAH后早期脑损伤中的神经保护作用及机制研究

蛛网膜下腔出血患者发病后30天内死亡率为50%，幸存者中近一半存在严重神经功能障碍。前期研究发现，过度激活的免疫炎症反应是导致脑损伤的主要机制之一。申请者先前研究发现，蛛网膜下腔出血后脑内激活的小胶质细胞会趋化外周免疫细胞进入脑损伤部位。采用单细胞RNA测序研究发现，趋化进入的调节性T细胞具有抑制免疫炎症反应和释放神经营养因子的作用。据此我们提出以下假设：蛛网膜下腔出血后被小胶质细胞趋化进入脑内的调节性T细胞能够通过释放神经营养因子直接保护神经元，以及释放IL10抑制小胶质细胞介导的炎症反应间接保护神经元。本课题拟采用单细胞RNA测序、流式分选、CyTOF以及基因调控等多种技术，结合模式动物和人脑组织标本，阐明调节性T细胞在蛛网膜下腔出血中神经保护作用的机制，为其治疗提供新的策略。

Almost 50% patients with subarachnoid hemorrhage die within 30 days after onset, and nearly half of the survivors have severe neurological disorders. Previous studies have indicated that overactivated immune inflammatory response is one of the main mechanisms leading to brain injury. Our previous study found that activated microglia recruited peripheral immune cells into the brain injury site after subarachnoid hemorrhage. Using single cell RNA sequencing, we observed that the infiltrated regulatory T cells could release neurotrophic factors and suppress overactivated immune inflammatory response. Hence, we propose the hypothesis that the infiltrated regulatory T cells can protect neurons directly by releasing neurotrophic factors and indirectly by releasing IL10 to inhibit microglial-mediated inflammation. This study aims to explore the neuroprotective mechanisms of the infiltrated regulatory T cells in neuron protection after subarachnoid hemorrhage by using single cell RNA sequencing, flow cytometry, and CyTOF, combined with model animal and human brain tissues, so as to provide a new strategy for the treatment of subarachnoid hemorrhage.