TY - JOUR
T1 - Premarin stimulates estrogen receptor-α to protect against traumatic brain injury in male rats
AU - Chen, Sheng Hsien
AU - Chang, Chia Yu
AU - Chang, Hsiu Kang
AU - Chen, Wei Chun
AU - Lin, Mao Tsun
AU - Wang, Jhi Joung
AU - Chen, Jeffrey Cheng Yu
AU - Chang, Fong Ming
PY - 2009/12
Y1 - 2009/12
N2 - 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.
AB - 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.
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U2 - 10.1097/CCM.0b013e3181bc7986
DO - 10.1097/CCM.0b013e3181bc7986
M3 - Article
C2 - 19789448
AN - SCOPUS:73349089967
SN - 0090-3493
VL - 37
SP - 3097
EP - 3106
JO - Critical care medicine
JF - Critical care medicine
IS - 12
ER -