Tanaka Miki, Ishihara Yasuhiro, Mizuno Shodo, Ishida Atsuhiko, Vogel Christoph F, Tsuji Mayumi, Yamazaki Takeshi, Itoh Kouichi
Laboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima University, Hiroshima, 739-8521, Japan; Laboratory for Pharmacotherapy and Experimental Neurology, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Kagawa, 769-2193, Japan.
Laboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima University, Hiroshima, 739-8521, Japan; Center for Health and the Environment, University of California, Davis, Davis, CA, 95616, USA.
Biochem Biophys Res Commun. 2018 Feb 5;496(2):582-587. doi: 10.1016/j.bbrc.2018.01.094. Epub 2018 Jan 17.
Brain edema is a severe complication that accompanies ischemic stroke. Increasing evidence shows that inflammatory cytokines impair tight junctions of the blood-brain barrier, suggesting the involvement of microglia in brain edema. In this study, we examined the role of microglia in the progression of ischemic brain edema using mice with permanent middle cerebral artery occlusion. The intensity of T2-weighted imaging (T2WI) in the cerebral cortex and the striatum was elevated 3 h after occlusion and spread to peripheral regions of the ischemic hemisphere. Merged images of 2,3,5-triphenyl tetrazolium chloride staining and T2WI revealed the exact vasogenic edema region, which spread from the ischemic core to outside the ischemic region. Microglia were strongly activated in the ischemic region 3 h after occlusion and, notably, activated microglia were observed in the non-ischemic region 24 h after occlusion. Pretreatment with minocycline, an inhibitor of microglial activation clearly suppressed not only vasogenic edema but also infarct formation. We demonstrated in this study that vasogenic edema spreads from the ischemic core to the peripheral region, which can be elicited, at least in part, by microglial activation induced by ischemia.
脑水肿是缺血性中风伴随的一种严重并发症。越来越多的证据表明，炎性细胞因子会损害血脑屏障的紧密连接，这表明小胶质细胞参与了脑水肿的形成。在本研究中，我们使用永久性大脑中动脉闭塞的小鼠，研究了小胶质细胞在缺血性脑水肿进展中的作用。闭塞后3小时，大脑皮质和纹状体的T2加权成像（T2WI）强度升高，并扩散至缺血半球的周边区域。2,3,5-三苯基氯化四氮唑染色与T2WI的融合图像显示了确切的血管源性水肿区域，该区域从缺血核心扩散至缺血区域之外。闭塞后3小时，小胶质细胞在缺血区域强烈激活，值得注意的是，闭塞后24小时在非缺血区域也观察到了激活的小胶质细胞。用小胶质细胞激活抑制剂米诺环素预处理，不仅明显抑制了血管源性水肿，还抑制了梗死形成。我们在本研究中证明，血管源性水肿从缺血核心扩散至周边区域，这至少部分是由缺血诱导的小胶质细胞激活引起的。
