title: Aggravated inflammation and increased expression of cysteinyl leukotriene receptors in the brain after focal cerebral ischemia in AQP4-deficient mice.
abstract: 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 min of middle cerebral arterial occlusion (MCAO). Ischemic neuronal injury and cellular inflammatory responses, as well as the expression and localization of cysteinyl leukotriene CysLT(2) and CysLT(1) 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 CysLT(1) and CysLT(2) receptors were up-regulated in the ischemic brain, and the up-regulation was more pronounced in AQP4-KO mice. The CysLT(1) and CysLT(2) receptors were primarily localized in neurons, microglia and neutrophils; those localized in microglia and neutrophils were enhanced in AQP4-KO mice.
  
  
  CONCLUSIONS
  AQP4 may play an inhibitory role in postischemic inflammation.
authors.affiliation: Institute of Neuroscience and Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, China.
authors.forename: Wen-Zhen
authors.initials: WZ
authors.lastname: Shi
authors.forename: Chun-Zhen
authors.initials: CZ
authors.lastname: Zhao
authors.forename: Bing
authors.initials: B
authors.lastname: Zhao
authors.forename: Qiao-Juan
authors.initials: QJ
authors.lastname: Shi
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Zhang
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Wang
authors.forename: San-Hua
authors.initials: SH
authors.lastname: Fang
authors.forename: Yun-Bi
authors.initials: YB
authors.lastname: Lu
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zhang
authors.forename: Er-Qing
authors.initials: EQ
authors.lastname: Wei
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000172:deficiency* / Q000235:genetics; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D007962:Leukocytes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018077:Receptors, Leukotriene / Q000096:biosynthesis*; D015854:Up-Regulation; D014869:Water Intoxication / Q000378:metabolism
chemical_list: D051401:Aquaporin 4; D018077:Receptors, Leukotriene; C083169:leukotriene D4 receptor