Aggravated chronic brain injury after focal cerebral ischemia in aquaporin-4-deficient mice.
The water channel aquaporin-4 (AQP4) is important in brain water homeostasis, and is also involved in astrocyte growth and glial scar formation. It has been reported that AQP4 deficiency attenuates acute ischemic brain injury as a result of reducing cytotoxic edema. Here, we determined whether AQP4 deficiency influences chronic brain injury after focal cerebral ischemia induced by 30 min of middle cerebral artery occlusion (MCAO). AQP4(-/-) mice exhibited a lower survival rate and less body weight gain than wild-type mice, but their neurological deficits were similar to wild-type mice during 35 days after MCAO. At 35 days after MCAO, AQP4(-/-) mice showed more severe brain atrophy and cavity formation in the ischemic hemisphere as well as more neuronal loss in the hippocampus. Furthermore, astrocyte proliferation and glial scar formation were impaired in AQP4(-/-) mice. Therefore, AQP4 deficiency complicated by astrocyte dysfunction aggravates chronic brain injury after focal cerebral ischemia, suggesting that AQP4 may be important in the chronic phase of the post-ischemic recovery process.
Institute of Neuroscience Research and Department of Pharmacology, School of Medicine, Zhejiang University, 388 Yu Hang Tang Road, Hangzhou 310058, China.
Wen-Zhen
WZ
Shi
Ling-Ling
LL
Qi
San-Hua
SH
Fang
Yun-Bi
YB
Lu
Wei-Ping
WP
Zhang
Er-Qing
EQ
Wei
D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics* / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D002470:Cell Survival; D002908:Chronic Disease; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology
C496031:Aqp4 protein, mouse; D051401:Aquaporin 4