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: Hiroya Akabori, Fariba Moeinpour, Kirby I Bland, Irshad H Chaudry
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 33 Issue 1 Pg. 43-8 (Jan 2010) ISSN: 1540-0514 [Electronic] United States
• PMID: 19536048 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Tumor Necrosis Factor-alpha
• Estradiol

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Brain (drug effects, immunology, pathology)
• Cells, Cultured
• Enzyme-Linked Immunosorbent Assay
• Estradiol (pharmacology, therapeutic use)
• Flow Cytometry
• Hemorrhage (drug therapy, immunology)
• In Vitro Techniques
• Male
• Microglia (drug effects, immunology, pathology)
• Rats
• Rats, Sprague-Dawley
• Tumor Necrosis Factor-alpha (blood, metabolism)