医学
冲程(发动机)
缺血性中风
雌激素受体
雌激素
内科学
受体
心脏病学
内分泌学
缺血
乳腺癌
癌症
机械工程
工程类
作者
Bradley Randal Scott Broughton,Vanessa H Brait,Hyun Ah Kim,Seyoung Sandy Lee,Hannah X Chu,Chantelle V. Gardiner-Mann,Elizabeth Guida,Megan C. Evans,Alyson A. Miller,Thiruma V. Arumugam,Grant Raymond Drummond,Christopher G. Sobey
出处
期刊:Stroke
[Ovid Technologies (Wolters Kluwer)]
日期:2014-03-01
卷期号:45 (3): 835-841
被引量:89
标识
DOI:10.1161/strokeaha.113.001499
摘要
Experimental studies indicate that estrogen typically, but not universally, has a neuroprotective effect in stroke. Ischemic stroke increases membrane-bound G protein-coupled estrogen receptor (GPER) distribution and expression in the brain of male but not female mice. We hypothesized that GPER activation may have a greater neuroprotective effect in males than in females after stroke.Vehicle (dimethyl sulfoxide), a GPER agonist (G-1, 30 μg/kg), or a GPER antagonist (G-15, 300 μg/kg) were administered alone or in combination to young or aged male mice, or young intact or ovariectomized female mice, 1 hour before or 3 hours after cerebral ischemia-reperfusion. Some mice were treated with a combination of G-1 and the pan-caspase inhibitor, quinoline-Val-Asp(Ome)-CH2-O-phenoxy (Q-VD-OPh), 1 hour before stroke. We evaluated functional and histological end points of stroke outcome up to 72 hours after ischemia-reperfusion. In addition, apoptosis was examined using cleaved caspase-3 immunohistochemistry.Surprisingly, G-1 worsened functional outcomes and increased infarct volume in males poststroke, in association with an increased expression of cleaved caspase-3 in peri-infarct neurons. These effects were blocked by G-15 or Q-VD-OPh. Conversely, G-15 improved functional outcomes and reduced infarct volume after stroke in males, whether given before or after stroke. In contrast to findings in males, G-1 reduced neurological deficit, apoptosis, and infarct volume in ovariectomized females, but had no significant effect in intact females.Future therapies for acute stroke could exploit the modulation of GPER activity in a sex-specific manner.
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