Estrogen therapy for experimental intracerebral hemorrhage in rats.

Abstract

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.

• Authors: Takehiro Nakamura, Ya Hua, Richard F Keep, Jung-Weon Park, Guohua Xi, Julian T Hoff
• Journal: Journal of neurosurgery (J Neurosurg) Vol. 103 Issue 1 Pg. 97-103 (Jul 2005) ISSN: 0022-3085 [Print] United States
• PMID: 16121980 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Estrogen Antagonists
• Receptors, Estrogen
• Fulvestrant
• Estradiol
• Heme Oxygenase (Decyclizing)
• Heme Oxygenase-1

Topics

• Animals
• Brain (drug effects, metabolism)
• Brain Edema (etiology, metabolism, prevention & control)
• Cerebral Hemorrhage (complications)
• Disease Models, Animal
• Drug Administration Schedule
• Estradiol (administration & dosage, analogs & derivatives, pharmacology)
• Estrogen Antagonists (pharmacology)
• Female
• Fulvestrant
• Heme Oxygenase (Decyclizing) (drug effects, metabolism)
• Heme Oxygenase-1
• Male
• Rats
• Rats, Sprague-Dawley
• Receptors, Estrogen (drug effects)
• Sex Factors