title: 17β-Estradiol attenuates secondary injury through activation of Akt signaling via estrogen receptor alpha in rat brain following subarachnoid hemorrhage.
abstract: BACKGROUND
  Apoptosis is implicated in vasospasm and the long-term sequelae of subarachnoid hemorrhage (SAH). This study tested the hypothesis that attenuation of SAH-induced apoptosis after 17β-estradiol (E2) treatment is associated with an increase in phosphorylation of Akt via estrogen receptor-α (ER-α) in rats.
  
  
  METHODS
  We examined the expression of phospho-Akt, ERα and ERβ, and apoptosis in cerebral cortex, hippocampus, and dentate gyrus in a two-hemorrhage SAH model in rats. We subcutaneously implanted other rats with a silicone rubber tube containing E2; they received daily injections of nonselective estrogen receptor antagonist (ICI 182,780), selective ERα-selective antagonist (methyl-piperidino-pyrazole), or ERβ-selective antagonist (R,R-tetrahydrochrysene) after the first hemorrhage.
  
  
  RESULTS
  At 7 d after the first SAH, protein levels of phospho-Akt and ERα were significantly decreased and caspase-3 was significantly increased in the dentate gyrus. The cell death assay revealed that DNA fragmentation was significantly increased in the dentate gyrus. Those actions were reversed by E2 and blocked by ICI 182,780 and methyl-piperidino-pyrazole, but not R,R-tetrahydrochrysene. However, there were no significant changes in the expression of the protein levels of phospho-Akt, ERα, ERβ, and caspase-3, and DNA fragmentation after SAH.
  
  
  CONCLUSIONS
  The present study shows that a beneficial effect of E2 in attenuating SAH-induced apoptosis is associated with activation of the expression of phospho-Akt and ERα, and alteration in caspase-3 protein expression via an ERα-dependent mechanism in the dentate gyrus. These data support further the investigation of E2 in the treatment of SAH in humans.
authors: Center for General Education, Southern Taiwan University of Technology, Tainan, Taiwan.
authors: Cheng-Hsing
authors: CH
authors: Kao
authors: Chih-Zen
authors: CZ
authors: Chang
authors: Yu-Feng
authors: YF
authors: Su
authors: Yee-Jean
authors: YJ
authors: Tsai
authors: Kao-Ping
authors: KP
authors: Chang
authors: Tzu-Kang
authors: TK
authors: Lin
authors: Shiuh-Lin
authors: SL
authors: Hwang
authors: Chih-Lung
authors: CL
authors: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis; D001930:Brain Injuries / Q000209:etiology / Q000517:prevention & control; D053148:Caspase 3 / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D004958:Estradiol / Q000627:therapeutic use*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000627:therapeutic use*; D008297:Male; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D004958:Estradiol; D051057:Proto-Oncogene Proteins c-akt; C505410:Casp3 protein, rat; D053148:Caspase 3