Aggravated inflammation and increased expression of cysteinyl leuko-triene receptors in the brain after focal cerebral ischemia in AQP4-deficient mice  

作　　者：Wen-Zhen Shi Chun-Zhen Zhao Bing Zhao Qiao-Juan Shi Li-Hui Zhang Yan-Fang Wang San-Hua Fang Yun-Bi Lu Wei-Ping Zhang Er-Qing Wei 

机构地区：[1]Institute of Neuroscience and Department of Pharmacology,School of Medicine,Zhejiang University [2]Hangzhou Key Laboratory of Neurobiology and Department of Pharmacology,School of Basic Medicine,Hangzhou Normal University

出　　处：《Neuroscience Bulletin》2012年第6期680-692,共13页神经科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China(81273491, 81072618,30772561 and 30873053);the Natural Science Foundation of Zhejiang Province,China(Y2090069);the"Qianjiang Rencai Research Plan"of Zhejiang Province China(2010R10055);the Fundamental Research Funds for the Central Universities,China(2009QNA7008)

摘　　要：Objective Aquaporin-4 （AQP4）, the main water channel protein in the brain, plays a critical role in water homeostasis and brain edema. Here, we investigated its role in the inflammatory responses after focal cerebral ischemia. Methods In AQP4-knockout （KO） and wild-type mice, focal cerebral ischemia was induced by 30 rain of middle cerebral arterial occlusion （MCAO）. Ischemic neuronal injury and cellular inflammatory responses, as well as the expression and localization of cysteinyl leukotriene CysLT2 and CysLT~ receptors, were determined at 24 and 72 h after MCAO. Results AQP4-KO mice showed more neuronal loss, more severe microglial activation and neutrophil infiltration, but less astrocyte proliferation in the brain after MCAO than wild-type mice. In addition, the protein levels of both CysLT1 and CysLT2 receptors were up-regulated in the ischemic brain, and the up-regulation was more pronounced in AQP4-KO mice. The CysLT1 and CysLT2 receptors were primarily localized in neurons, microglia and neutrophils; those localized in microglia and neutrophils were enhanced in AQP4-KO mice. Conclusion AQP4 may play an inhibitory role in postischemic inflammation.Objective Aquaporin-4 （AQP4）, the main water channel protein in the brain, plays a critical role in water homeostasis and brain edema. Here, we investigated its role in the inflammatory responses after focal cerebral ischemia. Methods In AQP4-knockout （KO） and wild-type mice, focal cerebral ischemia was induced by 30 rain of middle cerebral arterial occlusion （MCAO）. Ischemic neuronal injury and cellular inflammatory responses, as well as the expression and localization of cysteinyl leukotriene CysLT2 and CysLT~ receptors, were determined at 24 and 72 h after MCAO. Results AQP4-KO mice showed more neuronal loss, more severe microglial activation and neutrophil infiltration, but less astrocyte proliferation in the brain after MCAO than wild-type mice. In addition, the protein levels of both CysLT1 and CysLT2 receptors were up-regulated in the ischemic brain, and the up-regulation was more pronounced in AQP4-KO mice. The CysLT1 and CysLT2 receptors were primarily localized in neurons, microglia and neutrophils; those localized in microglia and neutrophils were enhanced in AQP4-KO mice. Conclusion AQP4 may play an inhibitory role in postischemic inflammation.

关 键 词：aquaporin 4 gene deficiency INFLAMMATION cysteinyl leukotriene receptor MICROGLIA ASTROCYTE focal cerebral ischemia 

分 类 号：R743[医药卫生—神经病学与精神病学]