title: Estrogen reduces iron-mediated brain edema and neuronal death.
abstract: Our previous studies found that 17-beta estradiol attenuates edema formation after intracerebral hemorrhage (ICH). As brain iron overload occurs after ICH and contributes to ICH-induced brain injury, the present study examined the effects of estrogen on iron-induced brain injury in vivo and in vitro.There were two sets of experiments in this study. In the first set, male Sprague-Dawley rats were pretreated with 17-beta estradiol or vehicle prior to an intracerebral injection of ferrous iron. Ferrous iron was injected into the right caudate and the rats were killed 24 h later for brain edema measurement. In the second set, primary cultured neurons were pretreated with different doses of 17-beta estradiol or vehicle for 24 h. The cells were then exposed to ferrous iron for 48 h when culture medium was collected for lactate dehydrogenase measurement. Neuronal death was also assessed by live/dead cell assay.Estrogen pretreatment reduced brain water content (p < 0.01) 24 h after iron injection. Estrogen also protected against iron-induced cell death in cultured neurons. Estrogen reduces iron-induced brain edema in vivo and neuronal death in vitro suggesting estrogen could be a potential therapeutic agent for ICH.
authors.affiliation: R5018 Biomedical Science Research Building, Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109-2200, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Gu
authors.forename: G
authors.initials: G
authors.lastname: Xi
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: R F
authors.initials: RF
authors.lastname: Keep
authors.forename: Y
authors.initials: Y
authors.lastname: Hua
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002543:Cerebral Hemorrhage / Q000150:complications; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology* / Q000627:therapeutic use; D004967:Estrogens / Q000494:pharmacology* / Q000627:therapeutic use; D007839:Functional Laterality; D007501:Iron / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004967:Estrogens; D004958:Estradiol; D007501:Iron; D007770:L-Lactate Dehydrogenase