title: Estrogen attenuates nuclear factor-kappa B activation induced by transient cerebral ischemia.
abstract: The protective effects of estrogens have been widely reported in a number of animal and cell culture models, but the molecular mechanisms of this potent neuroprotective activity are not well understood. Both in vitro and in vivo studies indicate that in the central nervous system and peripheral tissues, estrogen treatment reduces cytokine production and inflammatory responses. Nuclear factor-kappa B (NFkappaB) plays an essential role in the regulation of post-ischemic inflammation, which is detrimental to recovery from an ischemic stroke. We investigated the role of NFkappaB in neuronal survival in rats that received transient middle cerebral artery (MCA) occlusion, and observed that this transient cerebral ischemia induced substantial apoptosis and inflammatory responses, including IkappaB phosphorylation, NF-kappaB activation and iNOS over-expression. 17 beta-estradiol (E2) treatment produced strong protective effects by reducing infarct volume, neuronal apoptosis, and inflammatory responses. These findings provide evidence for a novel molecular and cellular interaction between the sex hormone and the immunoresponsive system. These studies also provide evidence that suppression of post-ischemic inflammation may play a critical role in estrogen-mediated neuroprotection.
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd., Fort Worth, TX 76107-2699, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wen
authors.forename: Shaohua
authors.initials: S
authors.lastname: Yang
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.forename: Evelyn
authors.initials: E
authors.lastname: Perez
authors.forename: Kun Don
authors.initials: KD
authors.lastname: Yi
authors.forename: Peter
authors.initials: P
authors.lastname: Koulen
authors.forename: James W
authors.initials: JW
authors.lastname: Simpkins
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D053938:DNA Fragmentation; D003720:Densitometry; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology*; D020768:Middle Cerebral Artery / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D018696:Neuroprotective Agents; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000199:Actins; D018836:Inflammation Mediators; D016328:NF-kappa B; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D004958:Estradiol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat