Estrogen therapy for experimental intracerebral hemorrhage in rats

OBJECT: The aims of this study were to determine the following: whether there are sex differences in intracerebral hemorrhage (ICH) induced brain injury in rats, whether delayed administration of 17beta-estradiol can reduce ICH-induced brain damage, and whether these effects are estrogen receptor (ER)-dependent. METHODS: Male and female Sprague-Dawley rats received an infusion of 100 microl autologous whole blood into the right basal ganglia. Twenty-four hours later the rats were killed. The effects of 17beta-estradiol on ICH-induced brain injury were examined by measuring brain edema and neurological deficits. Both ER-alpha and hemeoxygenase (HO)-1 were investigated through Western blot and immunohistochemical analysis. Brain edema was significantly less severe in female compared with that in male rats. The ER antagonist ICI 182,780 exacerbated ICH-induced brain edema in female but not in male rats, indicating that ER-alpha activation during ICH is protective in female rats. Administration of exogenous 17beta-estradiol in male, but not in female, rats significantly attenuated brain edema, neurological deficits, and ICH-induced changes in HO-1 when given 2 hours after hemorrhage. The effects of exogenous 17beta-estradiol occurred through an ER-independent mechanism. CONCLUSIONS: Results in this study indicate that 17beta-estradiol could be a potential therapeutic agent for ICH.