Estrogen and Bcl-2: Gene induction and effect of transgene in experimental stroke

Nabil J. Alkayed, Shozo Goto, Nubuo Sugo, Hung Dong Joh, Judith Klaus, Barbara J. Crain, Ora Bernard, Richard J. Traystman, Patricia D. Hurn

Research output: Contribution to journalArticlepeer-review

176 Scopus citations


Female rodents producing endogenous estrogens are protected from stroke damage in comparison with male counterparts. This natural protection is lost after ovariectomy or reproductive senescence. The aim of this study is to determine whether estrogen reduces early neuronal injury and cell loss after ischemia by increasing the expression of Bcl-2. Male, intact female, ovariectomized, and estrogen-repleted ovariectomized rats were subjected to middle cerebral artery occlusion, and 22 hr later the level and localization of Bcl-2 mRNA and protein were determined. The levels of post-ischemic bcl-2 mRNA and protein were increased exclusively in neurons within the peri-infarct region. Intact females and estrogen-treated castrates demonstrated increased bcl-2 mRNA and protein expression compared with males and estrogen-deficient females, accompanied by a decrease in infarct size. To test the hypothesis that the neuroprotective mechanism of estrogen functions via Bcl-2, we compared ischemic outcome in male, female, and ovariectomized wild-type mice and mice overexpressing Bcl-2 exclusively in neurons. Wild-type female mice sustained smaller infarcts compared with males. Bcl-2 overexpression reduced infarct size in males, but provided no added protection in the female. Moreover, ovariectomy exacerbated infarction in wild-type females, but had no effect in Bcl-2 overexpressors. These data indicate that overexpression of Bcl-2 simulates the protection against ischemic injury conferred by endogenous female sex steroids. We concluded that estrogen rescues neurons after focal cerebral ischemia by increasing the level of Bcl-2 in peri-infarct regions and that estrogen-induced bcl-2 gene expression is an important downstream component of neuronal protection in female stroke.

Original languageEnglish (US)
Pages (from-to)7543-7550
Number of pages8
JournalJournal of Neuroscience
Issue number19
StatePublished - Oct 1 2001
Externally publishedYes


  • Bcl-2
  • Cerebral ischemia
  • Estrogen
  • Female
  • Gender differences
  • Male
  • Neuronal cell death
  • Neuroprotection
  • Sex
  • Stroke

ASJC Scopus subject areas

  • General Neuroscience


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