title: Reduced brain edema and infarct volume in aquaporin-4 deficient mice after transient focal cerebral ischemia.
abstract: Aquaporin-4 (AQP4) is a water channel expressed in astrocyte end-feet lining the blood-brain barrier. AQP4 deletion in mice is associated with improved outcomes in global cerebral ischemia produced by transient carotid artery occlusion, and focal cerebral ischemia produced by permanent middle cerebral artery occlusion (MCAO). Here, we investigated the consequences of 1-h transient MCAO produced by intraluminal suture blockade followed by 23 h of reperfusion. In nine AQP4(+/+) and nine AQP4(-/-) mice, infarct volume was significantly reduced by an average of 39 ± 4% at 24h in AQP4(-/-) mice, cerebral hemispheric edema was reduced by 23 ± 3%, and Evans Blue extravasation was reduced by 31 ± 2% (mean ± SEM). Diffusion-weighted magnetic resonance imaging showed greatest reduction in apparent diffusion coefficient around the occlusion site after reperfusion, with remarkably lesser reduction in AQP4(-/-) mice. The reduced infarct volume in AQP4(-/-) mice following transient MCAO supports the potential utility of therapeutic AQP4 inhibition in stroke.
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, CA 94143, USA; Brain and Spinal Injury Center, University of California, San Francisco, CA 94143, USA; Departments of Medicine and Physiology, University of California, San Francisco, CA 94143, USA. Electronic address: xiaoming.yao@ucsf.edu.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, CA 94143, USA; Brain and Spinal Injury Center, University of California, San Francisco, CA 94143, USA.
authors.forename: Nikita
authors.initials: N
authors.lastname: Derugin
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, CA 94143, USA; Brain and Spinal Injury Center, University of California, San Francisco, CA 94143, USA.
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Manley
authors.affiliation: Departments of Medicine and Physiology, University of California, San Francisco, CA 94143, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Verkman
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics*; D001929:Brain Edema / Q000378:metabolism / Q000473:pathology*; D020520:Brain Infarction / Q000378:metabolism / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018345:Mice, Knockout
chemical_list: D051401:Aquaporin 4
keywords: AQP4; Blood–brain barrier; Brain edema; Transient cerebral ischemia