Ovariectomy exacerbates and estrogen replacement attenuates photothrombotic focal ischemic brain injury in rats
Ovariectomy exacerbates and estrogen replacement attenuates photothrombotic focal ischemic brain injury in rats
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DOI：
10.1161/01.str.31.1.155
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发表时间：
2000-01-01
期刊：
影响因子：
8.3
通讯作者：
Fujishima, M
中科院分区：
文献类型：
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作者：
Fukuda, K;Yao, HR;Fujishima, M
背景和目的：我们以前报道过雌性自发性高血压大鼠（SHR）的梗死体积明显小于雄性SHR。本研究的目的是确定是否雌激素是负责的性别差异，缺血性中风在SHR。方法在实验1，1周（短期）或4周（长期）后，卵巢切除术（OVX），雌性SHR（5个月大）随机进行光血栓闭塞大脑中动脉，梗死体积进行了测定。在实验2中，将大鼠随机分为3组（即假卵巢切除组、卵巢切除组和雌激素替代组）。在替代组中，戊酸雌二醇（200 μ g/kg）在OVX后每周皮下注射一次。激光多普勒血流仪测定局部脑血流量的变化。结果：实验一，去卵巢后1周脑梗死体积与假去卵巢组无明显差异。相反，OVX后4周产生的梗死体积明显大于假卵巢切除组（82.4 ± 11.6 vs51.5 ± 16.0 mm（3），P=0.0058）。在实验2中，与去卵巢组相比，去卵巢后补充雌二醇可减少梗死体积（55.6 ± 18.8 vs 78.5 ± 21.0 mm（3），P=0.0321）。区域脑血流量减少的程度并没有不同的假卵巢切除，卵巢切除，雌激素替代groups. Conclusions慢性雌激素耗竭，从而发现增加梗死面积，这是减弱雌二醇替代。这些发现表明，雌激素有助于缺血性脆弱性的性别差异，内源性雌激素也对缺血性脑损伤具有神经保护作用。
Background and Purpose-We previously reported the infarct volumes in female spontaneously hypertensive rats (SHR) to be significantly smaller than those in male SHR. The purpose of the present study was to determine whether estrogen is responsible for the sex difference in ischemic vulnerability in SHR.Methods-In experiment 1, 1 week (short-term) or 4 weeks (long-term) after the ovariectomy (OVX), female SHR (5 months old) were randomly subjected to photothrombotic occlusion of the middle cerebral artery, and the infarct volumes were determined. In experiment 2, the rats were randomly assigned to 3 groups (ie, the sham-ovariectomized, ovariectomized, and estrogen replacement groups). In the replacement group, estradiol valerate (200 mu g/kg) was subcutaneously injected once a week after the OVX, Four weeks after the OVX or sham-OVX, all rats were subjected to middle cerebral artery occlusion. Changes in regional cerebral blood flow were determined by laser-Doppler flowmetry,Results-In experiment 1, the infarct volume produced 1 week after the OVX was not different from that of the sham-ovariectomized group. In contrast, the infarct volume produced 4 weeks after the OVX was significantly larger than that of the sham-ovariectomized group (82.4+/-11.6 versus 51.5+/-16.0 mm(3), P=0.0058). In experiment 2, estradiol replacement after the OVX was observed to attenuate the infarct volume compared with the ovariectomized group (55.6+/-18.8 versus 78.5+/-21.0 mm(3), P=0.0321). The degrees of regional cerebral blood flow reduction did not differ among the sham-ovariectomized, ovariectomized, and estrogen replacement groups.Conclusions-Chronic estrogen depletion was thus found to increase the infarct size, which was attenuated by estradiol replacement. These findings indicate that estrogen contributes to the sex difference in ischemic vulnerability and that endogenous estrogen also has a neuroprotective effect against ischemic brain damage.