Neuroprotective effects of estradiol in middle-aged female rats

Estrogen replacement therapy in postmenopausal women ameliorates cognitive dysfunction and decreases the risk and/or severity of neurodegenerative con ditions such as Alzheimer's disease and stroke. Furthermore, estradiol exer ts neuroprotective effects in a variety of in vitro and in vivo models of b rain injury. We have previously shown that physiological levels of estradio l attenuate ischemic brain injury in young female rats. However, neurodegen erative events occur more frequently in elderly women who are chronically h ypoestrogenic. Therefore, we investigated whether aging rats remain respons ive to the neuroprotective actions of estradiol. Young (3-4 months) and mid dle-aged (9-12 months) rats were ovariectomized and treated for 1 week with estradiol before middle cerebral artery occlusion (MCAO). Regional cerebra l blood flow was monitored in some animals at the time of injury. Brains we re collected 24 h after MCAO and infarct volume was analyzed. Our data demo nstrate that in both young and aging rats, low and high physiological doses of estradiol decrease ischemic injury by almost 50%, compared with oil-tre ated controls. Additionally, our data suggest that estradiol acts in both a ge groups via blood flow-independent mechanisms, as basal and postinjury bl ood 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 prote ctive actions of estradiol.