17β-Estradiol reduces stroke injury in estrogen-deficient female animals

Renata Rusa, Nabil J. Alkayed, Barbara J. Crain, Richard J. Traystman, Alane S. Kimes, Edythe D. London, Judy A. Klaus, Patricia D. Hurn

Research output: Contribution to journalArticle

Abstract

Background and Purpose - The importance of postmenopausal estrogen replacement therapy for stroke in females remains controversial. We previously showed that female rats sustain less infarction in reversible middle cerebral artery occlusion (MCAO) than their ovariectomized counterparts and that vascular mechanisms are partly responsible for improved tissue outcomes. Furthermore, exogenous estrogen strongly protects the male brain, even when administered in a single injection before MCAO injection. The present study examined the hypothesis that replacement of 17β-estradiol to physiological levels improves stroke outcome in ovariectomized, estrogen- deficient female rats, acting through blood flow-mediated mechanisms. Methods - Age-matched, adult female Wistar rats were ovariectomized and treated with 0, 25, or 100 μg of 17 β-estradiol administered through a subcutaneous implant or with a single Premarin (USP) injection (1 mg/kg) given immediately before ischemia was induced (n=10 per group). Each animal subsequently underwent 2 hours of MCAO by the intraluminal filament technique, followed by 22 hours of reperfusion. Ipsilateral parietal cortex perfusion was monitored by laser-Doppler flowmetry throughout ischemia. Cortical and caudate-putamen infarction volumes were determined by 2,3,5-triphenyltetrazolium chloride staining and digital image analysis. End-ischemic regional cerebral blood flow was measured in ovariectomized females with 0- or 25-μg implants (n=4 per group) by 14C-iodoantipyrine quantitative autoradiography. Results - Plasma estradiol levels were 3.0±0.6, 20±8, and 46±10 pg/mL in the 0-, 25- , and 100-μg groups, respectively. Caudate-putamen infarction (% of ipsilateral Caudate-putamen) was reduced by long-term, 25-μg estrogen treatment (13±4% versus 31±6% in the 0-μg group, P

Original languageEnglish (US)
Pages (from-to)1665-1670
Number of pages6
JournalStroke
Volume30
Issue number8
Publication statusPublished - Aug 1999

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Keywords

  • 17β-estradiol
  • Cerebral blood flow
  • Cerebral ischemia
  • Estrogen replacement therapy
  • Rats
  • Stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Rusa, R., Alkayed, N. J., Crain, B. J., Traystman, R. J., Kimes, A. S., London, E. D., ... Hurn, P. D. (1999). 17β-Estradiol reduces stroke injury in estrogen-deficient female animals. Stroke, 30(8), 1665-1670.