少突胶质细胞是脑缺血损伤的重要靶细胞，AMPA受体介导钙超载所致兴奋性毒性是其主要致伤机制之一，但缺血后少突胶质细胞膜表面钙通透性AMPA受体增多的分子机制不明。GluR2是决定AMPA受体钙通透性的关键亚基，预实验显示脑缺血引起少突胶质细胞GluR2(Q/R)编辑效率降低，这可能是钙通透性AMPA受体增多的重要原因。本项目以GluR2亚基为重点，通过形态学、免疫印迹、RNA干扰、阻断剂等方法，观察脑缺血后少突胶质细胞GluR2(Q/R)编辑效率、定向移动及再循环过程的改变，系统地证明脑缺血一方面导致GluR2编辑效率降低、"钙通透性AMPA受体"生成增多，另一方面引起GRIP大量表达，加速GluR2(Q)亚基运输和循环，使大量"钙通透性AMPA受体"迅速锚定于膜表面，引发少突胶质细胞损伤。本课题将深化对缺血性少突胶质细胞损伤发生机制的理解，为发现新的白质保护治疗靶点提供理论基础和实验依据

Oligodendrocyte is an important cellular target in cerebral ischemic insult, with excitoxicity caused by calcium overload through AMPA receptors as a main potential mechnism. But the underlying mechanism how the sufrace expression of calcium-permeable AMPA (Cp-AMPA) receptors increased after ischemic insult is not clear yet. The calcium conductance of AMPA recptors is determined by GluR2 subunit. Our preliminary experiments showed a decrease in GluR2 (Q/R) site editing, which may significantly contribute to the increase of Cp-AMPA receptors. The project mainly focuses on GluR2 subunit, to investigate the influence of ischemia on the editing, trafficking and recycle of GluR2 by performing morphological analysis, western blot, RNA interence and blocking analysis, etc. It aims to elucidate that the cerebral ischemia leads to the drop of GluR2 editing efficiency which results in the increased biogenesis of Cp-AMPA recptors and also the increase of GRIP to speed up the GluR2(Q) trafficking and recycling. Subsequent booming membrane-anchoring of Cp-AMPA recptors results in oligodendrocyte injury. The project may deepen the understanding of the mechanism of ischemic oligodendrocyte injury, and furthermore provide theoretical basis and laboratory evidences for the new therapeutic target of white matter protection.