Estrogen therapy for experimental intracerebral hemorrhage in rats.
OBJECTIVE
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.
Nakamura
Takehiro
T
Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan 48109-0532, USA.
Hua
Ya
Y
Keep
Richard F
RF
Park
Jung-Weon
JW
Xi
Guohua
G
Hoff
Julian T
JT
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D002543:Cerebral Hemorrhage / Q000150:complications*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects / Q000378:metabolism; D051547:Heme Oxygenase-1; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000187:drug effects; D012737:Sex Factors
D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1