血脑屏障（BBB）结构和功能破坏是缺血性脑水肿的重要病理基础。星形胶质细胞是维持BBB结构完整的重要组分，但是星形胶质细胞中哪些关键分子和机制控制其在BBB通透性中的作用尚不完全清楚。NDRG2是本校生化教研室发现并克隆的一个基因，在脑中主要表达于星形胶质细胞。我们近期研究发现：体外培养的Ndrg2-/-小鼠星形胶质细胞突起长度明显缩短，突起数目显著减少；脑缺血后，Ndrg2-/-小鼠BBB结构破坏程度、BBB通透性、星形胶质细胞终足肿胀程度均明显高于野生小鼠。提示NDRG2可能通过调控星形胶质细胞维持BBB稳定。本课题拟从分子、细胞和动物三个水平，深入研究NDRG2调控星形胶质细胞形态和功能的分子机制；在生理和病理两个层次，阐明NDRG2在维持BBB稳定、减轻缺血性脑水肿中的作用。本研究将拓展星形胶质细胞维持BBB完整的机制认识，为缺血性脑水肿的防治提供新理论和新策略。

The disruption of blood brain barrier (BBB) is a main pathological basis in ischemic brain edema. Astrocytes is a vital component of BBB, however, the key molecules and mechanisms in astrocytes, which are involved in BBB permeability, are largely unknown. NDRG2 is a gene, which was first discovered and cloned in a laboratory of the Department of Biochemistry and Molecular Biology in our University. In the brain, NDRG2 mainly expresses in astrocytes. Our recent study showed: the length of cell processes were significantly shortened and the number of cell processes were obviously reduced in cultured Ndrg2-/- astrocytes; BBB structure damage, BBB permeability, and astrocytes swelling in the brain of Ndrg2-/- mice were significantly higher than the wild-type littermates after ischemia. These findings suggest that NDRG2 is involved in maintaining the stability of BBB by controlling astrocytes. This project intends to investigate the molecular mechanisms that NDRG2 regulates the cell morphology and function of astrocytes on molecular, cellular and animal-based levels. In addition, another goal of this project is to clarify the roles of NDRG2 in maintaining BBB structural integrity and alleviating ischemic brain edema under physiological and pathological conditions. This study will expand the knowledge in the function and mechanism of astrocyte-mediated BBB structural integrity, and provide novel theories and strategies for the prevention and treatment of ischemic brain edema.