ArticleJournal of neuroinflammation2017
Bazedoxifene, a selective estrogen receptor modulator, reduces cerebral aneurysm rupture in Ovariectomized rats.
Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 31 citations in OpenAlex.
- Bazedoxifene and Beyond: Identifying This SERM's Targets and Deciphering Its Molecular Mechanisms.Advances in pharmacological and pharmaceutical sciences · 2026Review
- GPER1/ACACB are potential target genes associated with intracranial aneurysm and vascular endothelial cell senescence.Neurosurgical review · 2025Article
- Sex differences in patients with and without high-risk factors associated with aneurysmal subarachnoid hemorrhage.Acta neurochirurgica · 2024Article
- Clinical characteristics of intracranial aneurysms in elderly patents over 70 years old: a retrospective observational study.BMC neurology · 2022Observational
- Integrated analysis identifies the IL6/JAK/STAT signaling pathway and the estrogen response pathway associated with the pathogenesis of intracranial aneurysms.Frontiers in immunology · 2022Article
- Why Are Women Predisposed to Intracranial Aneurysm?Frontiers in cardiovascular medicine · 2022Review
- Endogenous animal models of intracranial aneurysm development: a review.Neurosurgical review · 2021Review
- Estrogen receptor involvement in vascular cognitive impairment and vascular dementia pathogenesis and treatment.GeroScience · 2021Review
- Preclinical Intracranial Aneurysm Models: A Systematic Review.Brain sciences · 2020Review
- Berberine Ameliorates Subarachnoid Hemorrhage InjuryFrontiers in pharmacology · 2020Article
- Bazedoxifene Attenuates Abdominal Aortic Aneurysm FormationFrontiers in pharmacology · 2020Article
- Intracranial Aneurysm as a Macrophage-mediated Inflammatory Disease.Neurologia medico-chirurgica · 2019Article
- Macrophage Polarization in Cerebral Aneurysm: Perspectives and Potential Targets.Journal of immunology research · 2017Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEstrogen deficiency is thought to be responsible for the higher frequency of aneurysmal subarachnoid hemorrhage in post- than premenopausal women. Estrogen replacement therapy appears to reduce this risk but is associated with significant side effects. We tested our hypothesis that bazedoxifene, a clinically used selective estrogen receptor (ER) modulator with fewer estrogenic side effects, reduces cerebral aneurysm rupture in a new model of ovariectomized rats.
methodsTen-week-old female Sprague-Dawley rats were subjected to ovariectomy, hemodynamic changes, and hypertension to induce aneurysms (ovariectomized aneurysm rats) and treated with vehicle or with 0.3 or 1.0 mg/kg/day bazedoxifene. They were compared with sham-ovariectomized rats subjected to hypertension and hemodynamic changes (HT rats). The vasoprotective effects of bazedoxifene and the mechanisms underlying its efficacy were analyzed.
resultsDuring 12 weeks of observation, the incidence of aneurysm rupture was 52% in ovariectomized rats. With no effect on the blood pressure, treatment with 0.3 or 1.0 mg/kg/day bazedoxifene lowered this rate to 11 and 17%, almost the same as in HT rats (17%). In ovariectomized rats, the mRNA level of ERα, ERβ, and the tissue inhibitor of metalloproteinase-2 was downregulated in the cerebral artery prone to rupture at 5 weeks after aneurysm induction; the mRNA level of interleukin-1β and the matrix metalloproteinase-9 was upregulated. In HT rats, bazedoxifene restored the mRNA level of ERα and ERβ and decreased the level of interleukin-1β and matrix metalloproteinase-9. These findings suggest that bazedoxifene was protective against aneurysmal rupture by alleviating the vascular inflammation and degradation exacerbated by the decrease in ERα and ERβ.
conclusionsOur observation that bazedoxifene decreased the incidence of aneurysmal rupture in ovariectomized rats warrants further studies to validate this response in humans.
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