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(Stroke. 2000;31:738.)
© 2000 American Heart Association, Inc.
Original Contributions |
Stroke in Estrogen Receptor-
–Deficient Mice
From the Departments of Anesthesiology and Critical Care Medicine (K.S., S.G., N.J.A., M.S., R.J.T., P.D.H.) and of Pathology (B.J.C.), Johns Hopkins University School of Medicine, Baltimore, Md; the Laboratory of Reproductive and Developmental Toxicology (K.S.K.), National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC; and the Department of Psychology (G.E.D., R.J.N.), Johns Hopkins University, Baltimore, Md.
Correspondence to Patricia D. Hurn, PhD, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 600 N Wolfe St, Blalock 1404, Baltimore MD 21287. E-mail phurn{at}jhmi.edu
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-
(ER) is important to estrogen’s signaling in
the ischemic brain, then ER-deficient (knockout) (ERKO)
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 ERKO 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 ER
deficiency in female mice: 51.9±10.6 mm3 in ERKO
versus 60.5±5.0 mm3 in WT. Striatal infarction was
equivalent, 12.2±1.7 mm3 in ERKO 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 ERKO versus 30.6±4.1 mm3 in
WT). Intraocclusion blood flow to the parietal cortex was higher in
ERKO 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 ER 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.
Editorial Comment
Department of Pharmacology, College of Medicine, University of California, Irvine
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