17β-estradiol reduces stroke injury in estrogen-deficient female animals
17β-estradiol reduces stroke injury in estrogen-deficient female animals
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DOI：
10.1161/01.str.30.8.1665
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发表时间：
1999-08-01
期刊：
影响因子：
8.3
通讯作者：
Hurn, PD
中科院分区：
文献类型：
--
作者：
Rusa, R;Alkayed, NJ;Hurn, PD
背景和目的-绝经后雌激素替代治疗对女性卒中的重要性仍然存在争议。我们以前的研究表明，雌性大鼠在可逆性大脑中动脉闭塞（MCAO）中的梗死比卵巢切除后的大鼠少，血管机制是改善组织结局的部分原因。此外，外源性雌激素强烈保护男性大脑，即使在MCAO注射前单次注射给药。本研究检验了将17 β-雌二醇替换到生理水平的假设，其通过血流介导的机制起作用，改善了卵巢切除的雌激素缺乏的雌性大鼠的中风结果。或通过皮下植入物给予100 μ g 17 β-雌二醇，或在诱导缺血前立即给予单次倍美力（USP）注射液（1 mg/kg）（每组n = 10）。每只动物随后通过管腔内细丝技术进行2小时的MCAO，然后再灌注22小时。在整个缺血过程中，通过激光多普勒血流仪监测同侧顶叶皮质灌注。皮质和尾壳核梗死。通过氯化2，3，5-三苯基四唑染色和数字图像分析测定体积。用C-14-iodoantipyrine定量放射自显影术测定了卵巢切除的女性植入0-或25-μ g植入物（每组n=4）的终末缺血局部脑血流量。结果0-，25-和100-μ g组的血浆雌二醇水平分别为3.0+/-0.6，20 +/-8，46 +/-10 pg/mL。尾壳核梗死（占同侧尾壳核的%）在长期25 μ g雌激素治疗后减少（13+/-4%vs31 +/-6%，0 μ g组，P
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 17 beta-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 mu g of 17 beta-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-mu g implants (n=4 per group) by C-14-iodoantipyrine quantitative autoradiography.Results-Plasma estradiol levels were 3.0+/-0.6, 20+/-8, and 46+/-10 pg/mL in the 0-, 25-, and 100-mu g groups, respectively. Caudate-putamen infarction (% of ipsilateral caudate-putamen) was reduced by long-term, 25-mu g estrogen treatment (13+/-4% versus 31+/-6% in the 0-mu g group, P