Effects of Gender and Estrogen Receptors on Iron-Induced Brain Edema Formation

Abstract

Our previous studies have shown that female mice have less brain edema and better recovery in neurological deficits after intracerebral hemorrhage (ICH) and that 17β-estradiol treatment in male mice markedly reduces ICH-induced brain edema. In this study, we investigated the role of gender and the estrogen receptors (ERs) in iron-induced brain edema. There were three parts in this study: (1) either male or female mice received an injection of 10 μL FeCl₂ (1 mM) into the right caudate; (2) females received an intracaudate injection of FeCl₂ or saline with 1 μg of ICI 182,780 (antagonists of ERs) or vehicle; and (3) males were treated with the ER regulator tamoxifen (5 mg/kg subcutaneously) or vehicle 1 h after FeCl₂ injection. Mice were euthanized 24 h later for brain edema determination. FeCl₂ induced lower brain edema in females than in males. Co-injection of ICI 182,780 with FeCl₂ aggravated iron-induced brain edema in female mice. ICI 182,780 itself did not induce brain edema at the dose of 1 μg. Tamoxifen treatment reduced FeCl₂-induced brain edema in male mice. In conclusion, iron induced less brain edema in female mice than in males. ER modification can affect iron-induced brain edema.

This study was supported by grants NS-073595, NS-079157, and NS-084049 from the National Institutes of Health (NIH); and NSFC30901549 from National Science Foundation of China.