Worsened Outcome from Middle Cerebral Artery Occlusion in Aged Rats Receiving 17β-Estradiol

Although estrogens are neuroprotective in young adult animal models of stroke, clinical trials demonstrate that estrogens increase the incidence and severity of stroke in aged women. We have previously shown that experimental stroke pathophysiology differs between young adult and aged rats. The aim of this study was to determine the effects of 17β-estradiol after middle cerebral artery occlusion and reperfusion in young adult and aged female rats. Focal embolic stroke was performed by middle cerebral artery occlusion with fibrin clot followed by reperfusion with iv human recombinant tissue plasminogen activator. Histological and functional outcomes were measured at 24 h after middle cerebral artery occlusion with fibrin clot. Aged rats treated with 17β-estradiol had significantly increased infarct volumes compared with placebo-treated aged rats. Young adult rats treated with 17β-estradiol had significantly decreased infarct volumes and improved functional outcome compared with ovariectomized young adult rats. Our results suggest that 17β-estradiol may act in an age-dependent manner in the postischemic rat brain. In young adult rats, it is neuroprotective; chronic treatment with 17β-estradiol during aging leads to worsened ischemic brain injury in aged female rats.