Bazedoxifene, a selective estrogen receptor modulator, reduces cerebral aneurysm rupture in Ovariectomized rats

• Material Type: 博士論文
• Title: Bazedoxifene, a selective estrogen receptor modulator, reduces cerebral aneurysm rupture in Ovariectomized rats
• Author/Editor: Maekawa, Hidetsugu; Tada, Yoshiteru; Yagi, Kenji; Miyamoto, Takeshi; Kitazato, Keiko T.; Korai, Masaaki; Satomi, Junichiro; Hashimoto, Tomoki; Nagahiro, Shinji
• Author Heading: Maekawa, Hidetsugu; Tada, Yoshiteru; Yagi, Kenji; Miyamoto, Takeshi; Kitazato, Keiko T.; Korai, Masaaki; Satomi, Junichiro; Hashimoto, Tomoki; Nagahiro, Shinji
• Publication, Distribution, etc.: Springer nature
• Publication Date: 2017-10-02
• Publication Date (W3CDTF): 2017-10-02
• Alternative Title: 選択的エストロゲン受容体モジュレーターのバゼドキシフェンは卵巣摘除ラットにおいて脳動脈瘤破裂を抑制する
• Periodical title: Journal of Neuroinflammation
• No. or year of volume/issue: 14
• Volume: 14
• Pages: 197-
• ISSN (Periodical Title): ISSN : 1742-2094
• Degree grantor/type: 徳島大学
• Date Granted: 2018-03-22
• Dissertation Number: 甲第3125号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: estrogen; estrogen receptor; intracranial aneurysm; selective estrogen receptor modulator; subarachnoid hemorrhage
• Target Audience: 一般
• Note (General): Background: Estrogen 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. Methods: Ten-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. Results: During 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. Conclusions: Our observation that bazedoxifene decreased the incidence of aneurysmal rupture in ovariectomized rats warrants further studies to validate this response in humans.
• Format (IMT): application/pdf
• Source: fulltext; https://repo.lib.tokushima-u.ac.jp/files/public/11/111431/20180417112245308239/k3125_abstract_review.pdf; https://repo.lib.tokushima-u.ac.jp/files/public/11/111431/20180417112245636567/k3125_fulltext.pdf
• Access Restrictions: インターネット公開
• Rights (production): © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
• Related Material (DOI): 10.1186/s12974-017-0966-7
• Periodical Title (NCID): AA12051048; https://ci.nii.ac.jp/ncid/AA12051048
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ