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
Neurosurgeryjournal_title
Neurosurgeryauthors
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 Tdoi
10.1227/NEU.0000000000000528subject
Has Abstractpub_date
2014-12-01 00:00:00pages
690-5; discussion 695issue
6eissn
0148-396Xissn
1524-4040journal_volume
75pub_type
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