Dubal D B, Wise P M
Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky 40536-0298, USA.
Endocrinology. 2001 Jan;142(1):43-8. doi: 10.1210/endo.142.1.7911.
Estrogen replacement therapy in postmenopausal women ameliorates cognitive dysfunction and decreases the risk and/or severity of neurodegenerative conditions such as Alzheimer's disease and stroke. Furthermore, estradiol exerts neuroprotective effects in a variety of in vitro and in vivo models of brain injury. We have previously shown that physiological levels of estradiol attenuate ischemic brain injury in young female rats. However, neurodegenerative events occur more frequently in elderly women who are chronically hypoestrogenic. Therefore, we investigated whether aging rats remain responsive to the neuroprotective actions of estradiol. Young (3-4 months) and middle-aged (9-12 months) rats were ovariectomized and treated for 1 week with estradiol before middle cerebral artery occlusion (MCAO). Regional cerebral blood flow was monitored in some animals at the time of injury. Brains were collected 24 h after MCAO and infarct volume was analyzed. Our data demonstrate that in both young and aging rats, low and high physiological doses of estradiol decrease ischemic injury by almost 50%, compared with oil-treated controls. Additionally, our data suggest that estradiol acts in both age groups via blood flow-independent mechanisms, as basal and postinjury blood flow was equivalent between estradiol- and oil-treated young and aging rats. These data demonstrate that replacement with physiological levels of estradiol protects against stroke-related injury in young and aging female rats and strongly suggest that older animals remain responsive to the protective actions of estradiol.
绝经后女性的雌激素替代疗法可改善认知功能障碍，并降低患神经退行性疾病（如阿尔茨海默病和中风）的风险及/或严重程度。此外，雌二醇在多种脑损伤的体外和体内模型中发挥神经保护作用。我们之前已经表明，生理水平的雌二醇可减轻年轻雌性大鼠的缺血性脑损伤。然而，神经退行性事件在长期雌激素水平低下的老年女性中更为常见。因此，我们研究了衰老大鼠是否仍对雌二醇的神经保护作用有反应。将年轻（3 - 4个月）和中年（9 - 12个月）大鼠进行卵巢切除，并在大脑中动脉闭塞（MCAO）前用雌二醇治疗1周。在损伤时对一些动物的局部脑血流量进行监测。MCAO后24小时收集大脑并分析梗死体积。我们的数据表明，与用油处理的对照组相比，在年轻和衰老大鼠中，低剂量和高剂量的生理雌二醇均可使缺血性损伤降低近50%。此外，我们的数据表明，雌二醇在两个年龄组中均通过不依赖血流的机制起作用，因为在接受雌二醇和油处理的年轻和衰老大鼠中，基础血流和损伤后血流是相当的。这些数据表明，用生理水平的雌二醇替代可保护年轻和衰老雌性大鼠免受中风相关损伤，并强烈表明老年动物仍对雌二醇的保护作用有反应。
