神经损伤是蛛网膜下腔出血（SAH）高致死率和高致残率的重要原因。正常胶质细胞功能是维持神经元活动的重要保障。我们前期发现大鼠SAH模型中血肿周围脑组织和脑脊液中存在胶质细胞异质性，外泌体和microRNAs的差异表达，为此提出外泌体介导的microRNAs转运可能参与到SAH后神经-胶质网络以及神经损伤的调控中的假说。本项目将借助体内外SAH模型及临床病例，利用单细胞RNA测序和细胞分选技术，进一步完善SAH后胶质细胞异质性分析，建立针对不同胶质细胞亚型的体内外SAH模型；利用microRNAs高通量测序/过表达与干扰，外泌体收集/干预，电生理和行为学评分等技术，明确SAH后不同胶质细胞亚型的作用及作用机制；应用Cre重组酶转基因小鼠技术，探讨靶向特定胶质细胞亚型防治SAH后神经损伤的可能性。通过本研究深化胶质细胞在SAH后神经损伤中的作用，为建立SAH后神经损伤的临床治疗新方法奠定基础。

Neuronal injury after subarachnoid hemorrhage (SAH) is an important factor for SAH-induced high disability and mortality. Normal glial cell function is an important guarantee for maintaining neuronal activity. Our preliminary experimental results showed that the heterogeneity of glial cells, exosomes and differential expression of microRNAs existed in perihematomal brain tissue and cerebrospinal fluid in experimental rat SAH model. Thus, we propose the hypothesis: microRNAs transport mediated by exosomes may be involved in the regulation of neuro-glial networks and neuronal damage after SAH. By single cell RNA sequencing and cell separation technology, we will further improve the heterogeneity of glial cells assay under SAH stimulus and set up SAH model for different glial cells subtypes both in vivo and in vitro. Then, microRNAs high-throughput sequencing/overexpression and interference, exosomes collection/intervention, electrophysiological and behavioral assessment are used to evaluate the role and mechanism of different glial cell subtypes on neuronal injury after SAH. Finally, by Cre transgenic mouse technique, we will discuss the possibility of targeting specific glial cell subtypes for SAH-induced neuronal injury treatment. The outcome of this study will deepen the knowledge of the role of glial cells in SAH-induced neuronal injury, and pave the way for defining the new clinical strategy of SAH.