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Role of selective estrogen receptor modulators on cerebrovascular diseases

Research Project

Project/Area Number 26462159
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research Institution独立行政法人国立病院機構四国こどもとおとなの医療センター(臨床研究部(成育)、臨床研究部(循環器)) (2015-2016)
The University of Tokushima (2014)

Principal Investigator

Kuwayama Kazuyuki  独立行政法人国立病院機構四国こどもとおとなの医療センター(臨床研究部(成育)、臨, 臨床研究部, 脳神経外科医長 (50614236)

Co-Investigator(Kenkyū-buntansha) 里見 淳一郎  徳島大学, 大学院医歯薬学研究部(医学系), 准教授 (10304510)
多田 恵曜  徳島大学, 大学院医歯薬学研究部(医学系), 講師 (30547964)
永廣 信治  徳島大学, 大学院医歯薬学研究部(医学系), 教授 (60145315)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords脳血管病 / エストロゲン受容体α/β / エストロゲン受容体調節薬 / 脳動脈瘤破裂 / エストロゲン受容体作動薬(SERM) / エストロゲン受容体作動薬(SERM)
Outline of Final Research Achievements

Severe ischemic stroke and subarachnoid hemorrhage due to rupture of cerebral aneurysms are catastrophic and poor prognosis. Hormonal replacement therapy does not necessarily result in the good outcome. Elsewhere we demonstrated the beneficial role of estrogen receptors (ERs) against brain vascular diseases. In this study, we focused on the role of ERs. Since the affinity of estrogen to ERα is 1000 times higher than ERβ, ERα acts mainly under its presence. ERβ is thought to compensate when ERα is downregulated. We treated with a selective ER modulator (SERM) approved for osteoporosis in the cerebral aneurysm model rats. SERM was protective against cerebral aneurysm rupture; the inhibition of a cytokine, IL-1β and a vascular degradation molecule, MMP-9 by SERM was attributable to the efficacy. We are planning to identify the risk factors associated with the expression of cytokine and vascular degradation molecules and to clarify the role of SERM against cerebral ischemia.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (10 results)

All 2017 2016 2015 2014

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (3 results) (of which Int'l Joint Research: 3 results)

  • [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] 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] 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] Improvement of plasma biomarkers including angiotensin-(1-7) after switching from other angiotensin II type I receptor blockers to olmesartan in stroke patients with insufficient blood pressure control2015

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

      J stroke cerebrovasc dis

      Volume: in press

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intra-arterial signal on arterial spin labeling perfusion MRI to identify the presence of acute middle cerebral artery occlusion2014

    • Author(s)
      Tada Y, Satomi J, Abe T, Kuwayama K, Sogabe S, Fujita K, Yamamoto N, Kaji R, Harada M, Nagahiro S
    • Journal Title

      Cerebrovasc Dis

      Volume: 38 Pages: 191-196

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Estrogen protects against intracranial aneurysm rupture in ovariectomized mice2014

    • Author(s)
      Tada Y, Wada K, Shimada K, Makino H, Liang EI, Murakami S, Kudo M, Shikata F, Pena Silva RA, Kitazato KT, Hasan DM, Kanematsu Y, Nagahiro S, Hashimoto T
    • Journal Title

      Hypertension

      Volume: 63 Pages: 1339-1344

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [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, S. Nagahiro
    • 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
    • Int'l Joint Research
  • [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
    • Int'l Joint Research

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Published: 2014-04-04   Modified: 2018-03-22  

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