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Role of selective estrogen receptor modulator on the formation and rupture of intracranial aneurysms

Research Project

Project/Area Number 15K19972
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurosurgery
Research InstitutionThe University of Tokushima

Principal Investigator

TADA Yoshiteru  徳島大学, 大学院医歯薬学研究部(医学系), 講師 (30547964)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords脳・神経 / 脳神経疾患 / 選択的エストロゲン受容体作動薬 / 脳動脈瘤破裂 / くも膜下出血
Outline of Final Research Achievements

Estrogen and estrogen receptor agonist prevented the formation and rupture of intracranial aneurysms in animal models. However, estrogen replacement therapy is associated with side effects such as endometrial- and breast cancer. We tested our hypothesis that bazedoxifene, a clinically used selective estrogen receptor modulator with fewer estrogenic side effects, prevented aneurysmal rupture in our aneurysm model rats. Intracranial aneurysms were induced by hemodynamic stress, hypertension, and estrogen deficiency in female rats. Bazedoxifene prevented aneurysmal rupture without affecting the blood pressure. The protective effects against the aneurysmal rupture of bazedoxifene was associated with the increased expression of estrogen receptors and the decreased in the ratio of the matrix metalloproteinase-9 to the tissue inhibitor of metalloproteinase-2 expression.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (15 results)

All 2017 2016 2015 Other

All Int'l Joint Research (3 results) Journal Article (7 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (5 results) (of which Int'l Joint Research: 3 results)

  • [Int'l Joint Research] University of California, San Francisco(米国)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] University of Pennsylvania(米国)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] Toronto University(カナダ)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Intra-arterial high signals on arterial spin labeling perfusion images predict the occluded internal carotid artery segment2017

    • Author(s)
      Sogabe S, Satomi J, Tada Y, Kanematsu Y, Kuwayama K, Yagi K, Yoshioka S, Mizobuchi Y, Mure H, Yamaguchi I, Abe T, Yamamoto N, Kitazato KT, Kaji R, Harada M, Nagahiro S
    • Journal Title

      Neuroradiology.

      Volume: - Issue: 6 Pages: 587-595

    • DOI

      10.1007/s00234-017-1828-9

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Treatment Outcome of Carotid Artery Stenting Underwent within 14 Days of Stroke Onset – Consideration of Safety and Efficacy of Urgent Carotid Artery Stenting for Neurologically Progressing Patients2017

    • Author(s)
      Kanematsu Y, Satomi J, Kuwayama K, Yamaguchi I, Yoshioka S, Kinouchi T, Tada Y, Yamamoto N, Matsubara S, Satoh K, Nagahiro S
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 57 Issue: 6 Pages: 278-283

    • DOI

      10.2176/nmc.oa.2016-0236

    • NAID

      130006882460

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hyperhomocysteinemia induced by excessive methionine intake promotes rupture of cerebral aneurysms in ovariectomized rats, J Neuroinflammation2016

    • Author(s)
      Korai M, Kitazato KT, Tada Y, Miyamoto T, Shimada K, Matsushita N, Kanematsu Y, Satomi J, Hashimoto T, Nagahiro S
    • Journal Title

      J Neuroinflammation

      Volume: 13 Issue: 1 Pages: 165-175

    • DOI

      10.1186/s12974-016-0634-3

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Site-specific elevation of interleukin-1β and matrix metalloproteinase-9 in the Willis circle by hemodynamic changes is associated with rupture in a novel rat cerebral aneurysm model2016

    • Author(s)
      Miyamoto T, Kung DK, Kitazato KT, Yagi K, Shimada K, Tada Y, Korai M, Kurashiki Y, Kinouchi T, Kanematsu Y, Satomi J, Hashimoto T, Nagahiro S
    • Journal Title

      J Cereb Blood Flow Metab

      Volume: - Issue: 8 Pages: 2795-2805

    • DOI

      10.1177/0271678x16675369

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Angiotensin-(1-7) protects against the development of aneurysmal subarachnoid hemorrhage in mice2015

    • Author(s)
      Shimada K, Furukawa H, Wada K, Wei Y, Tada Y, Kuwabara A, Shikata F, Kanematsu Y, Lawton M, Kitazato K, Nagahiro S, Hashimoto T
    • Journal Title

      J Cereb Blood Flow Metab

      Volume: 35 Issue: 7 Pages: 1163-1168

    • DOI

      10.1038/jcbfm.2015.30

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Improvement of Plasma Biomarkers after Switching Stroke Patients from Other Angiotensin II Type I Receptor Blockers to Olmesartan2015

    • Author(s)
      Tada Y, Yagi K, Uno M, Matsushita N, Kanematsu Y, Kuwayama K, Shimada K, Nishi K, Hirasawa M, Satomi J, Kitazato KT, Kageji T, Matsuura E, Nagahiro S
    • Journal Title

      J Stroke Cerebrovasc Dis

      Volume: 24 Issue: 7 Pages: 1487-1492

    • DOI

      10.1016/j.jstrokecerebrovasdis.2015.03.015

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protective Role of Peroxisome Proliferator-Activated Receptor-γ in the Development of Intracranial Aneurysm Rupture2015

    • Author(s)
      Shimada K, Furukawa H, Wada K, Korai M, Wei Y, Tada Y, Kuwabara A, Shikata F, Kitazato KT, Nagahiro S, Lawton MT, Hashimoto T
    • Journal Title

      Stroke

      Volume: 46 Issue: 6 Pages: 1664-1672

    • DOI

      10.1161/strokeaha.114.007722

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Porphyromonas gingivalis lipopolysaccharide enhances the rupture of intracranial aneurysms in rats2016

    • Author(s)
      Miyamoto T, Kitazato K, Maekawa H,Yamaguchi T, Shimada K, Yagi K, Tada Y, Kurashiki Y, Yoshioka S, Kanematsu Y, Satomi J, Nagahiro S
    • Organizer
      25th European Stroke Conference
    • Place of Presentation
      Venice, Italy
    • Year and Date
      2016-04-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Activation of M2 macrophages in the late phase of cerebral ischemia may contribute to phagocytosis of infarct area and neurogenesis2016

    • Author(s)
      Kurashiki Y, Kitazato K, Shimada K, Yagi K, Tada Y, Kinouchi T, Sumiyoshi M, Miyamoto T, Yamaguchi T, Satomi J, Uto Y, Nagahiro S
    • Organizer
      25th European Stroke Conference
    • Place of Presentation
      Venice, Italy
    • Year and Date
      2016-04-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impact of Periodontal Disease and -Bacteria on Intracranial Aneurysms2016

    • Author(s)
      S. Yoshioka, Y. Tada, J. Satomi, K. Yagi, K. Naruishi, K. Kuwayama, K. T. Kitazato, T. Miyamoto, Y. Kanematsu, M. Harada, T. Nagata, Nagahiro S.
    • Organizer
      International Stroke Conference
    • Place of Presentation
      Los Angeles, USA
    • Year and Date
      2016-02-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Early Morphological Changes in Cerebral Arteries of Cerebral Aneurysm Rupture Model Rats2016

    • Author(s)
      H. Maekawa, T. Miyamoto, K.T. Kitazato, K. Yagi, Y. Tada, K. Shimada, J. Satomi, S Nagahiro.
    • Organizer
      International Stroke Conference
    • Place of Presentation
      Los Angeles, USA
    • Year and Date
      2016-02-17
    • Related Report
      2015 Research-status Report
  • [Presentation] A Pilot Study of the Mineralocorticoid Receptor Blocker Eplerenone in Hypertensive Patients with Unruptured Cerebral Aneurysms2016

    • Author(s)
      J. Satomi, Y. Tada, Y. Kanematsu, K. Kuwayama, K. Yagi, T. Kinouchi, K. Nakajima, N. Matsushita, T. Miyamoto, T. Yamaguchi, M. Korai, H. Mure, K. T. Kitazato, S Nagahiro.
    • Organizer
      International Stroke Conference
    • Place of Presentation
      Los Angeles, USA
    • Year and Date
      2016-02-17
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2022-02-22  

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