17β-Estradiol Reduces Stroke Injury in Estrogen-Deficient Female Animals

作者：Renata Rusa, Nabil J. Alkayed, Barbara J. Crain, Richard J. Traystman, Alane S. Kimes, Edythe D. London, Judy A Klaus, Patricia D. Hurn · 发表于：Stroke · 年份：1999 · DOI：10.1161/01.str.30.8.1665 · 被引用次数：307 · 研究领域：Menopause: Health Impacts and Treatments、Estrogen and related hormone effects、Neurological Disease Mechanisms and Treatments

BACKGROUND AND PURPOSE: The importance of postmenopausal estrogen replacement therapy for stroke in females remains controversial. We previously showed that female rats sustain less infarction in reversible middle cerebral artery occlusion (MCAO) than their ovariectomized counterparts and that vascular mechanisms are partly responsible for improved tissue outcomes. Furthermore, exogenous estrogen strongly protects the male brain, even when administered in a single injection before MCAO injection. The present study examined the hypothesis that replacement of 17beta-estradiol to physiological levels improves stroke outcome in ovariectomized, estrogen-deficient female rats, acting through blood flow-mediated mechanisms. METHODS: Age-matched, adult female Wistar rats were ovariectomized and treated with 0, 25, or 100 microgram of 17beta-estradiol administered through a subcutaneous implant or with a single Premarin (USP) injection (1 mg/kg) given immediately before ischemia was induced (n=10 per group). Each animal subsequently underwent 2 hours of MCAO by the intraluminal filament technique, followed by 22 hours of reperfusion. Ipsilateral parietal cortex perfusion was monitored by laser-Doppler flowmetry throughout ischemia. Cortical and caudate-putamen infarction volumes were determined by 2,3, 5-triphenyltetrazolium chloride staining and digital image analysis. End-ischemic regional cerebral blood flow was measured in ovariectomized females with 0- or 25-microgram implants (n...