Stroke in estrogen receptor-α-deficient mice

Kenji Sampei, Shozo Goto, Nabil J. Alkayed, Barbara J. Crain, Kenneth S. Korach, Richard J. Traystman, Gregory E. Demas, Randy J. Nelson, Patricia D. Hurn

Research output: Contribution to journalArticle


Background and Purpose - Recent evidence suggests that endogenous estrogens or hormone replacement therapy can ameliorate brain damage from experimental stroke. Protective mechanisms involve enhanced cerebral vasodilation during ischemic stress as well as direct preservation of neuronal viability. We hypothesized that if the intracellular estrogen receptor subtype-α (ERα) is important to estrogen's signaling in the ischemic brain, then ERα-deficient (knockout) (ERαKO) female mice would sustain exaggerated cerebral infarction damage after middle cerebral artery occlusion. Methods - The histopathology of cresyl violet-stained tissues was evaluated after reversible middle cerebral artery occlusion (2 hours, followed by 22 hours of reperfusion) in ERαKO transgenic and wild-type (WT) mice (C57BL/6J background strain). End-ischemic cerebral blood flow mapping was obtained from additional female murine cohorts by using [14C]iodoantipyrine autoradiography. Results - Total hemispheric tissue damage was not altered by ERα deficiency in female mice: 51.9 ± 10.6 mm3 in ERαKO versus 60.5±5.0 mm3 in WT. Striatal infarction was equivalent, 12.2+1.7 mm3 in ERαKO and 13.4±1.0 mm3 in WT mice, but cortical infarction was paradoxically smaller relative to that of the WT (20.7±4.5 mm3 in ERαKO versus 30.6±4.1 mm3 in WT). Intraocclusion blood flow to the parietal cortex was higher in ERαKO than in WT mice, likely accounting for the reduced infarction in this anatomic area. There were no differences in stroke outcomes by region or genotype in male animals. Conclusions - Loss of ERα does not enhance tissue damage in the female animal, suggesting that estrogen inhibits brain injury by mechanisms that do not depend on activation of this receptor subtype.

Original languageEnglish (US)
Pages (from-to)738-744
Number of pages7
Issue number3
Publication statusPublished - Mar 2000



  • Cerebral ischemia
  • Estrogen
  • Gender
  • Menopause
  • Stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Sampei, K., Goto, S., Alkayed, N. J., Crain, B. J., Korach, K. S., Traystman, R. J., ... Hurn, P. D. (2000). Stroke in estrogen receptor-α-deficient mice. Stroke, 31(3), 738-744.