title: 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.
authors.affiliation: Departments of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.|Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Departments of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Guohua
authors.initials: G
authors.lastname: Xi
authors.affiliation: Departments of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Keep
authors.affiliation: Departments of Neurosurgery, University of Michigan, Ann Arbor, MI, USA. yahua@umich.edu.
authors.forename: Ya
authors.initials: Y
authors.lastname: Hua
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001929:Brain Edema / Q000139:chemically induced* / Q000378:metabolism; D002421:Caudate Nucleus; D002712:Chlorides / Q000633:toxicity*; D004195:Disease Models, Animal; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D065171:Estrogen Receptor Antagonists / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D007501:Iron; D058085:Iron Compounds / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012737:Sex Factors; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D002712:Chlorides; D004965:Estrogen Antagonists; D065171:Estrogen Receptor Antagonists; D058085:Iron Compounds; D011960:Receptors, Estrogen; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol; D007501:Iron
keywords: Brain edema; Cerebral hemorrhage; Estrogen receptor; Iron; Tamoxifen