Roles of estrogen in the formation of intracranial aneurysms in ovariectomized female mice.

Abstract:

BACKGROUND:Epidemiological studies have indicated that postmenopausal women have a higher incidence of intracranial aneurysms than men in the same age group. OBJECTIVE:To investigate whether estrogen or estrogen receptors (ERs) mediate protective effects against the formation of intracranial aneurysms. METHODS:Intracranial aneurysms were induced in mice by combining a single injection of elastase into the cerebrospinal fluid with deoxycorticosterone acetate salt hypertension. The mice were treated with estrogen (17β-estradiol), an ERα agonist (propyl pyrazole triol), and an ERβ agonist (diarylpropionitrile) with and without a nitric oxide synthase inhibitor. RESULTS:The ovariectomized female mice had a significantly higher incidence of aneurysms than the male mice, which was consistent with findings in previous epidemiological studies. In ovariectomized female mice, an ERβ agonist, but not an ERα agonist or 17β-estradiol, significantly reduced the incidence of aneurysms. The protective effect of the ERβ agonist was absent in the ovariectomized ERβ knockout mice. The protective effect of the ERβ agonist was negated by treatment with a nitric oxide synthase inhibitor. CONCLUSION:The effects of sex, menopause, and estrogen treatment observed in this animal study were consistent with previous epidemiological findings. Stimulation of estrogen receptor-β was protective against the formation of intracranial aneurysms in ovariectomized female mice.

journal_name

Neurosurgery

journal_title

Neurosurgery

authors

Tada Y,Makino H,Furukawa H,Shimada K,Wada K,Liang EI,Murakami S,Kudo M,Kung DK,Hasan DM,Kitazato KT,Nagahiro S,Lawton MT,Hashimoto T

doi

10.1227/NEU.0000000000000528

subject

Has Abstract

pub_date

2014-12-01 00:00:00

pages

690-5; discussion 695

issue

6

eissn

0148-396X

issn

1524-4040

journal_volume

75

pub_type

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