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

Authors

Yoshiteru Tada, University of California, San Francisco
Hiroshi Makino, University of California, San Francisco
Hajime Furukawa, University of California, San Francisco
Kenji Shimada, University of California, San Francisco
Kosuke Wada, University of California, San Francisco
Elena I. Liang, University of California, San Francisco
Shoko Murakami, University of California, San Francisco
Mari Kudo, University of California, San Francisco
David K. Kung, University of Iowa Hospitals & Clinics
David M. Hasan, University of California, San Francisco
Keiko T. Kitazato, Tokushima University Faculty of Medicine
Shinji Nagahiro, Tokushima University Faculty of Medicine
Michael T. Lawton, University of California, San FranciscoFollow
Tomoki Hashimoto, University of California, San FranciscoFollow

Document Type

Article

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 (17b-estradiol), an ERa agonist (propyl pyrazole triol), and an ERb 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 ERb agonist, but not an ERa agonist or 17b-estradiol, significantly reduced the incidence of aneurysms. The protective effect of the ERb agonist was absent in the ovariectomized ERb knockout mice. The protective effect of the ERb 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-b was protective against the formation of intracranial aneurysms in ovariectomized female mice.

Publication Date

1-1-2014

Publication Title

Neurosurgery

ISSN

0148396X

E-ISSN

15244040

Volume

75

Issue

6

First Page

690

Last Page

695

PubMed ID

25181430

Digital Object Identifier (DOI)

10.1227/NEU.0000000000000528

Recommended Citation

Tada, Yoshiteru; Makino, Hiroshi; Furukawa, Hajime; Shimada, Kenji; Wada, Kosuke; Liang, Elena I.; Murakami, Shoko; Kudo, Mari; Kung, David K.; Hasan, David M.; Kitazato, Keiko T.; Nagahiro, Shinji; Lawton, Michael T.; and Hashimoto, Tomoki, "Roles of estrogen in the formation of intracranial aneurysms in ovariectomized female mice" (2014). Neurosurgery. 1094.
https://scholar.barrowneuro.org/neurosurgery/1094