Effects of endogenous and exogenous estrogen on intracerebral hemorrhage-induced brain damage in rats.

The present study examined differences in intracerebral hemorrhage (ICH)-induced brain injury in male and female rats, whether delayed administration of 17beta-estradiol can reduce ICH-induced brain damage, and whether these effects are estrogen receptor (ER)-dependent. Male and female Sprague-Dawley rats received an infusion of 100-microL autologous whole blood into the right basal ganglia. The effects of 1beta-estradiol (5 mg/kg, i.p.) on ICH-induced brain injury were examined by measuring brain edema and neurological deficits 24 hours later. Heme oxygenase-1 (HO-1) was investigated by immuno-analysis. Brain edema was significantly less in female compared to male rats. The ER antagonist ICI182,780 exacerbated ICH-induced brain edema in female but not in male rats, suggesting that ER activation during ICH is protective in female rats. Administration of 17beta-estradiol to male (but not female) rats significantly reduced brain edema, neurological deficits, and ICH-induced increases in brain HO-1 levels when given 2 hours after ICH. This study showed that female rats have less ICH-induced injury than male rats. ER is involved in limiting ICH-induced injury in female rats. ICH-injury in male rats can be reduced by 17beta-estradiol. Since 17beta-estradiol treatment was effective in male rats, it could be a potential therapeutic agent for ICH.