Estrogens may reduce mortality and ischemic damage caused by middle cerebral artery occlusion in the female rat

The present study was undertaken to determine if estrogens protect female rats from the neurodegenerative effects of middle cerebral artery (MCA) occlusion. The rats were ovariectomized and 7 or 8 days later various estrogen preparations were administered before or after MCA occlusion. Pretreatment with 17beta-estradiol (17beta-E2) or a brain-targeted 17beta-E2 chemical delivery system (CDS) decreased mortality from 65% in ovariectomized rats to 22% in 17beta-E2-treated and 16% in 17beta-E2 CDS-treated rats. This marked reduction in mortality was accompanied by a reduction in the ischemic area of the brain from 25.6+/-5.7% in the ovariectomized rats to 9.8+/-4% and 9.1+/-4.2% in the 17beta-E2-implanted and the 17beta-E2 CDS-treated rats, respectively. Similarly, pretreatment with the presumed inactive estrogen, 17alpha-estradiol, reduced mortality from 36 to 0% and reduced the ischemic area by 55 to 81%. When administered 40 or 90 minutes after MCA occlusion, 17beta-E2 CDS reduced the area of ischemia by 45 to 90% or 31%, respectively. In summary, the present study provides the first evidence that estrogens exert neuroprotective effects in an animal model of ischemia and suggests that estrogens may be a useful therapy to protect neurons against the neurodegenerative effects of stroke.