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(Stroke. 2000;31:155.)
© 2000 American Heart Association, Inc.

Original Contributions

Ovariectomy Exacerbates and Estrogen Replacement Attenuates Photothrombotic Focal Ischemic Brain Injury in Rats

Kenji Fukuda, MD; Hiroshi Yao, MD; Setsuro Ibayashi, MD; Tatsuo Nakahara, PhD; Hideyuki Uchimura, MD Masatoshi Fujishima, MD

From the Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka (K.F., H.Y., S.I., M.F.), and the Center for Emotional and Behavioral Disorders, Hizen National Hospital, Saga (K.F., H.Y., T.N., H.U.), Japan.

Correspondence to Kenji Fukuda, MD, Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka 812-8582, Japan.

Background and Purpose—We previously reported the infarct volumes in female spontaneously hypertensive rats (SHR) to be significantly smaller than those in male SHR. The purpose of the present study was to determine whether estrogen is responsible for the sex difference in ischemic vulnerability in SHR.

Methods—In experiment 1, 1 week (short-term) or 4 weeks (long-term) after the ovariectomy (OVX), female SHR (5 months old) were randomly subjected to photothrombotic occlusion of the middle cerebral artery, and the infarct volumes were determined. In experiment 2, the rats were randomly assigned to 3 groups (ie, the sham-ovariectomized, ovariectomized, and estrogen replacement groups). In the replacement group, estradiol valerate (200 µg/kg) was subcutaneously injected once a week after the OVX. Four weeks after the OVX or sham-OVX, all rats were subjected to middle cerebral artery occlusion. Changes in regional cerebral blood flow were determined by laser-Doppler flowmetry.

Results—In experiment 1, the infarct volume produced 1 week after the OVX was not different from that of the sham-ovariectomized group. In contrast, the infarct volume produced 4 weeks after the OVX was significantly larger than that of the sham-ovariectomized group (82.4±11.6 versus 54.5±16.0 mm³, P=0.0058). In experiment 2, estradiol replacement after the OVX was observed to attenuate the infarct volume compared with the ovariectomized group (55.6±18.8 versus 78.5±21.0 mm³, P=0.0321). The degrees of regional cerebral blood flow reduction did not differ among the sham-ovariectomized, ovariectomized, and estrogen replacement groups.

Conclusions—Chronic estrogen depletion was thus found to increase the infarct size, which was attenuated by estradiol replacement. These findings indicate that estrogen contributes to the sex difference in ischemic vulnerability and that endogenous estrogen also has a neuroprotective effect against ischemic brain damage.

Editorial Comment

Edward D. Hall, PhD, Guest Editor

Neuroscience Therapeutics, Parke-Davis Pharmaceutical Research, Ann Arbor, Michigan

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