创伤性脑损伤（TBI）发病率高，是导致青少年死亡的首要原因。数据显示TBI后引起的脑水肿是患者致死、致残的重要原因，但其病理过程十分复杂。研究发现TBI后AQP4蛋白的时空分布及表达变化是脑水肿形成、发展的重要诱因，但是这种变化导致了其下游哪些基因表达改变，以及其发生变化的机制尚不清楚。本项目拟联合显微光学切片断层成像（MOST）以及单细胞测序两种技术手段，分别从组织水平和分子水平阐述AQP4在创伤性脑水肿中的作用及机制。在组织水平上，利用MOST技术解析当脑水肿发生时，神经细胞的数量以及形态变化情况，以及当AQP4被特异沉默后神经细胞随之发生的改变。在分子水平上，利用单细胞测序技术解析损伤发生后各种细胞的比例以及基因表达变化情况，进一步分析AQP4空间分布及表达变化与导致TBI后脑水肿演变的相关分子机制，从而加深对创伤性脑水肿调控机制的认识。

The high incidence of Traumatic Brain Injury (TBI) is the leading cause of death in adolescents. The data show that cerebral edema caused by TBI is an important cause of death and disability of patients, however, the pathological process is very complicated. Researches show that the polar changes of AQP4 protein play a significant role in the formation of brain edema caused by traumatic brain injury. However, it is not clear which downstream genes are regulated by AQP4, how is its polar changed. This research will use micro-optical slice tomography (MOST) and single-cell sequencing technology to study the function of AQP4 in traumatic brain injury at both tissue and molecular levels. At the tissue level, using MOST technique to analyze the number and morphology of nerve cells when brain edema occurred, and the subsequent changes in nerve cells when AQP4 was specifically silenced. At the molecular level, single-cell sequencing technology will be used to analyze the proportion of various cells and gene expression changes after traumatic brain injury, and the molecular mechanism of AQP4 regulating polarity changes leading to brain edema also will be analyzed, so as to deepen the understanding of the pathogenesis of traumatic brain injury.