Effects of gender and estradiol treatment on focal brain ischemia.

The present studies were undertaken to investigate the effects of gender and estrogen treatment on focal cerebral ischemia in male and female rats. Focal ischemia was created by inserting a 3-0 surgical suture through the left cervical internal carotid artery to obstruct the blood flow into the middle cerebral artery (MCA). The MCA was reperfused by removing the suture in 40 min. All rats were sacrificed for measurement of infarct area after 24 h. In the first study, mortalities from MAC occlusion were 12.5% (2/16) each for intact male rats and intact female rats, and 23.5% (4/17) for ovariectomized (OVX) female rats. The coronal infarct area (mean+/-S. E.M.) was 9.5+/-1.0% for intact female rats, 16.6+/-1.6% for intact male rats (p=0.0001 vs. intact female rats), and 16.0+/-1.4% for OVX female rats (p=0.0002 vs. intact female rats). In a second experiment, OVX-female rats were administrated either 17beta-estradiol (E2) or its vehicle, hydroxypropyl-beta-cyclodextrin (HPCD), at 40 min after the onset of MCA occlusion. Mortalities were 40% (4/10) for vehicle treated OVX rats and 0% for E2 treated OVX rats. The coronal infarct area (mean+/-S.E.M.) was 19.3+/-1.8% for vehicle treated rats vs. 8.0+/-1. 2% for E2 treated rats (p<0.01). Serum estrogen levels for vehicle treated OVX rats were 14.5+/-1.2% pg/ml vs. 142.7+/-23.6 pg/ml for E2 treated OVX rats (p<0.01). These results strongly suggest that the level of circulating estrogens play an important role in protecting brain tissues against ischemia induced by MCA occlusion.