title: Mechanism of the anti-inflammatory effect Of 17beta-estradiol on brain following trauma-hemorrhage.
abstract: Although 17beta-estradiol (E2) is reported to improve the inflammatory response after trauma-hemorrhage (T-H), it remains unknown whether E2 plays any role in the central nervous system after T-H. Microglial cells, resident central macrophages, are thought to play a central role in exacerbating cell-mediated inflammation. We hypothesized that T-H up-regulates microglial cell-mediated inflammatory response in the brain, and E2 produces central anti-inflammatory effects via negative regulation of microglial cells. Male Sprague-Dawley rats were subjected to sham operation (cannulation plus laparotomy) or T-H (midline laparotomy; mean blood pressure, 35 +/- 5 mmHg for 90 min followed by resuscitation) and immediately killed after resuscitation. Rats received vehicle or E2 (1 mg/kg body weight i.v.) at the onset of resuscitation. In other experiments, minocycline (40 mg/kg body weight i.p.), microglia inhibitor, was administered 1 h before T-H to prevent inflammatory response in the microglia after T-H. The plasma and hypothalamic tumor necrosis factor (TNF-alpha) levels were increased, along with the activation of microglial cells in T-H rats compared with shams. Furthermore, T-H increased microglial TNF-alpha productive capacity in vitro. 17beta administration after T-H prevented these inflammatory responses. In rats pretreated with minocycline, decreased microglial TNF-alpha production and hypothalamic TNF-alpha levels were observed, but plasma TNF-alpha levels were not altered after T-H. Thus, T-H induces inflammatory responses even in the hypothalamus, and E2 seems to be a useful adjunct for down-regulating microglial cell-mediated inflammatory response after T-H.
authors.affiliation: Department of Surgery, Center for Surgical Research, University of Alabama at Birmingham, Alabama, USA.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Akabori
authors.forename: Fariba
authors.initials: F
authors.lastname: Moeinpour
authors.forename: Kirby I
authors.initials: KI
authors.lastname: Bland
authors.forename: Irshad H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000494:pharmacology* / Q000627:therapeutic use*; D005434:Flow Cytometry; D006470:Hemorrhage / Q000188:drug therapy* / Q000276:immunology; D066298:In Vitro Techniques; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol