Premarin stimulates estrogen receptor-α to protect against traumatic brain injury in male rats

Sheng Hsien Chen, Chia Yu Chang, Hsiu Kang Chang, Wei Chun Chen, Mao Tsun Lin, Jhi Joung Wang, Jeffrey Cheng Yu Chen, Fong Ming Chang

研究成果: Article同行評審

28 引文 斯高帕斯(Scopus)

摘要

Objective: To establish mechanisms of neuroprotective actions induced by Premarin (an estrogen sulfate) during traumatic brain injury. Design: Chi Mei Medical Center research laboratory. SUBJECTS: Male Sprague-Dawley rats 244 to 268 g. Interventions: Anesthetized rats, immediately after the onset of fluid percussion injury, were divided into three major groups and given the vehicle solution (1 mL/kg of body weight), Premarin (1 mg/kg of body weight), or Premarin (1 mg/kg of body weight) plus the nonselective estrogen receptor-α antagonist ICI 182, 780 (0.25 mg/kg of body weight) intravenously and immediately after fluid percussion injury. Measurements and main results: Premarin, in addition to inducing pharmacologic levels of estradiol, causes attenuation of fluid percussion injury-induced cerebral infarction and motor and cognitive function deficits. Fluid percussion injury-induced apoptosis (e.g., increased numbers of both terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive and caspase-3-positive cells) as well as activated inflammation (e.g., increased levels of tumor necrosis factor-α) was also significantly Premarin-reduced. In peri-ischemic areas of hippocampus, both angiogenesis (e.g., increased numbers of both 5-bromodeoxyuridine-positive endothelial and vascular endothelial growth factor-positive cells) and neurogenesis (e.g., increased numbers of both 5-bromodeoxyuridine/neuronal-specific nuclear protein double-positive and glial cell line-derived neurotrophic factor-positive cells) were Premarin therapy-promoted. In estrogen receptor-α blockade rats, Premarin therapy had less or no effect on fluid percussion injury-induced behavioral deficits, cerebral infarction and apoptosis, and activated inflammation. Furthermore, Premarin-induced angiogenesis and neurogenesis were estrogen receptor-α blockade-reduced. Conclusions: Our results indicate that pharmacologic levels of Premarin therapy-induced estradiol protect against cortical and hippocampal programmed cell death after fluid percussion injury through mechanisms stimulating estrogen receptor-α in the male rats.

原文English
頁(從 - 到)3097-3106
頁數10
期刊Critical care medicine
37
發行號12
DOIs
出版狀態Published - 2009 12月

All Science Journal Classification (ASJC) codes

  • 重症監護和重症監護醫學

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