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From the Department of Anesthesiology and Critical Care Medicine, Johns
Hopkins University School of Medicine (N.J.A., I.H., R.J.T., P.D.H.) and
National Institute on Drug Abuse (A.S.K., E.D.L.), Baltimore, Md.
Correspondence to Patricia D. Hurn, PhD, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, 600 N Wolfe St/Blalock 1404, Baltimore, MD 21287. E-mail phurn{at}welchlink.welch.jhu.edu
Background and Purpose—Premenopausal
women are at lower risk than men for stroke, but the comparative
vulnerability to tissue injury once a cerebrovascular incident occurs
is unknown. We hypothesized that female rats sustain less brain damage
than males during experimental focal ischemia and that the
gender difference in ischemic outcome can be eliminated by
ovariectomy.
Methods—Age-matched male (M), intact female (F), and
ovariectomized female (O; plasma estradiol: 4.1±1.6 pg/mL compared
with 7.4±1.5 in F and 4.0±1.1 in M) rats from two different strains,
normotensive Wistar and stroke-prone spontaneously hypertensive rats,
were subjected to 2 hours of intraluminal middle cerebral artery
occlusion, followed by 22 hours of reperfusion. Cerebral blood flow
(CBF) was monitored throughout the ischemic period by
laser-Doppler flowmetry. Infarction volume in the cerebral
cortex (Ctx) and caudoputamen (CP) was determined by
2,3,5-triphenyltetrazolium chloride
staining. In a separate cohort of M, F, and O Wistar rats, absolute
rates of regional CBF were measured at the end of the ischemic
period by quantitative autoradiography using
[14C]iodoantipyrine.
Results—F rats of either strain had a smaller infarct size in Ctx
and CP and a higher laser-Doppler flow during ischemia
compared with respective M and O rats. Mean end-ischemic CBF
was higher in F compared with M and O rats in CP, but not in Ctx.
Cerebrocortical tissue volume with end-ischemic CBF <10 mL/100
g/min was smaller in F than M rats, but not different from O rats.
Conclusions—We conclude that endogenous estrogen
improves stroke outcome during vascular occlusion by exerting both
neuroprotective and flow-preserving effects.
Director,
National Institute of Nursing Research,
National Institutes of Health,
Bethesda, Maryland
© 1998 American Heart Association, Inc.
Original Contributions
Gender-Linked Brain Injury in Experimental Stroke
Editorial Comment
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L. D. McCullough, N. J. Alkayed, R. J. Traystman, M. J. Williams, and P. D. Hurn Postischemic Estrogen Reduces Hypoperfusion and Secondary Ischemia After Experimental Stroke Stroke, March 1, 2001; 32(3): 796 - 802. [Abstract] [Full Text] [PDF]
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D. B. Dubal and P. M. Wise Neuroprotective Effects of Estradiol in Middle-Aged Female Rats Endocrinology, January 1, 2001; 142(1): 43 - 48. [Abstract] [Full Text] [PDF]
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