Conserved aquaporin 4 levels associated with reduction of brain edema are mediated by estrogen in the ischemic brain after experimental stroke |
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Authors: | Jin A. ShinJi Ha Choi Youn-Hee ChoiEun-Mi Park |
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Affiliation: | a Department of Pharmacology, Ewha Medical Research Institute, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Koreab Tissue Injury Defense Research Center, Ewha Medical Research Institute, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Koreac Department of Physiology, Ewha Medical Research Institute, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Koread Department of Brain and Cognitive Sciences, Brain Disease Research Institute, Ewha Womans University, Seoul 120-750, Republic of Korea |
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Abstract: | Aquaporin 4 (AQP4), the most abundant water channel protein in the brain, is involved in brain edema induced by ischemic insults. To evaluate whether the neuroprotective effects of estrogen are associated with AQP4 expression and edema formation, changes in AQP levels and ischemic edema were examined in the brains of male and female mice subjected to transient middle cerebral artery occlusion. Infarct volume and edema formation were markedly less in females than in males. AQP4 expression in the ischemic cortex of females was relatively well preserved, whereas it was significantly decreased in males. These effects disappeared in ovariectomized females but were reversed by estrogen replacement. Furthermore, AQP4 expression was decreased with increased brain edema in females treated with ICI182,780, an estrogen receptor antagonist. These findings suggest that the estrogen effect on the reduction of ischemic brain edema is associated with the preserved level of AQP4 that is partly mediated by estrogen receptors. |
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Keywords: | Aquaporin 4 Brain edema Estrogen Estrogen receptor Ischemic stroke Sex difference |
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