Dose dependence and therapeutic window for the neuroprotective effects of 17beta-estradiol when administered after cerebral ischemia.

The present study was undertaken to determine if the neuroprotective effect of 17beta-estradiol (E(2)) when administrated after ischemia is dose-dependent and if the therapeutic window for estrogen can be prolonged. Ischemic injury was induced by permanent middle cerebral artery occlusion (p-MCAO). Administration of E(2) at 30 min after ischemia resulted in a reduction in lesion volume. A higher dose of E(2) extended the therapeutic window to 6h after cerebral ischemia in 33% of the rats. These findings suggest that postischemic treatment with estrogen affords protection against ischemic damage and that it acts within a clinically useful therapeutic window.