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Molecular mechanisms underlying the rupture of cerebral aneurysms and the pharmacological regulation

Research Project

Project/Area Number 24390344
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Cerebral neurosurgery
Research InstitutionThe University of Tokushima

Principal Investigator

NAGAHIRO Shinji  徳島大学, ヘルスバイオサイエンス研究部, 教授 (60145315)

Co-Investigator(Kenkyū-buntansha) SATOMI Junichiro  徳島大学, 大学院ヘルスバイオサイエンス研究部, 准教授 (10304510)
TADA Yoshiteru  徳島大学, 大学院ヘルスバイオサイエンス研究部, 助教 (30547964)
KUWAYAMA Kauyuki  徳島大学, 病院, 講師 (50614236)
MORIGAKI Ryoma  徳島大学, 大学院ヘルスバイオサイエンス研究部, 特任助教 (70710565)
兼松 康久  徳島大学, 大学病院, 助教 (90363142)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2012: ¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000)
Keywords脳・神経 / 脳血管病 / エストロゲン / 脳動脈瘤破裂 / 血行動態変化 / 高血圧 / 結構動態変化 / 脳血管障害 / くも膜下出血 / 破裂脳動脈瘤 / 高塩食
Outline of Final Research Achievements

Subarachnoid hemorrhage is a catastrophic event and directs to high mobility and bad prognosis. To prevent this event, it is required to verify the pathogenesis. Hemodynamic stress is one of the initiating factors for cerebral aneurysmal formation. We hypothesized that additive hemodynamic change accelerates the development of aneurysms and studied the hypothesis. Ten-weeks-old Sprague-Dawley female rats were additively occluded in Rt.PPA and Rt.ECA. Their rupture incidence and the rupture rate were increased. The development of aneurysms at the circle of Willis may be partly attributable to hemodynamic change. Using this model we will study the efficacy of pharmacological treatment such as telmisartan, eplerenone or cilostazol. On the other hand, we started the clinical studies to assess the pharmacological treatment of cerebral aneurysms.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (22 results)

All 2015 2014 2013 2012

All Journal Article (8 results) (of which Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (14 results)

  • [Journal Article] Roles of Angiotensin (1-7) And Angiotensin II Type 2 Receptor on Intracranial Aneurysmal Rupture2015

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

      Stroke

      Volume: 45

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 MT, Kitazato KT, Nagahiro S, Hashimoto T
    • Journal Title

      J Cereb Blood Flow Metab

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Roles of estrogen in the formation of intracranial aneurysms in ovariectomized female mice2014

    • Author(s)
      Tada Y, Makino H, Furukawa H, Shimada K, Wada K, Liang EI, Murakami S, Kudo M, Kung DK, Kitazato KT, Nagahiro S, Lawton MT, Hashimoto T
    • Journal Title

      Neurosurgery

      Volume: 75 Pages: 690-695

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of hypertension in the rupture of intracranial aneurysms2014

    • Author(s)
      Tada Y, Wada K, Shimada K, Makino H, Liang EI, Murakami S, Kudo M, Kitazato KT, Nagahiro S, Hashimoto T
    • Journal Title

      Stroke

      Volume: 45 Pages: 579-586

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [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, Silva RAP, Kitazato KT, Hasan DM, Kanematsu Y, Nagahiro S, Hashimoto T
    • Journal Title

      Hypertension

      Volume: 63 Pages: 1339-1344

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [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: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 脳動脈瘤におけるNa+蓄積とRASの影響2013

    • Author(s)
      多田恵曜、北里慶子、永廣信治
    • Journal Title

      Angiotensin Research

      Volume: 10 Pages: 84-92

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Increase in body Na^<+->to^-water ratio is associated with cerebral aneurysm formation in oophorectomized rats2012

    • Author(s)
      Nobuhisa Matsushita, et al.
    • Journal Title

      Hypertension

      Volume: 60 Pages: 1309-1315

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Role of hyperhomocysteinemia in the development of intracranial aneurysms2015

    • Author(s)
      Korai M, Kitazato KT, Miyamoto T, Shimada K, Yagi K, Tada Y, Kurashiki Y, Kuwayama K, Satomi J, Nagahiro S
    • Organizer
      International Stroke Conference
    • Place of Presentation
      Nashville、USA
    • Year and Date
      2015-02-10 – 2015-02-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Hemodynamic change elicits the formation and rupture of experimental cerebral aneurysms2015

    • Author(s)
      Miyamoto T,, David K. Kung, Korai M, Kitazato KT, Shimada K, Yagi K, Tada Y, Kurashiki Y, Kuwayama K, Satomi J, Nagahiro S
    • Organizer
      International Stroke Conference
    • Place of Presentation
      Nashville、USA
    • Year and Date
      2015-02-10 – 2015-02-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Is the regulation of M1 macrophage activation beneficial in the acute phase of post cerebral ischemia?2015

    • Author(s)
      Kurashiki Y, Kitazato K, Uto Y, Yagi K, Shimada K, Miyamoto T, Sumiyoshi M, Tada Y, Kuwayama K, Satomi J, Nagahiro S
    • Organizer
      International Stroke Conference
    • Place of Presentation
      Nashville、USA
    • Year and Date
      2015-02-10 – 2015-02-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Protective effects of estrogen receptor-beta against the formation of intracranial aneurysms in mice2014

    • Author(s)
      Tada Y, Makino H., Wada K., Shimada K., Liang E., Murakami S., Kudo M, Kitazato KT., Nagahiro S., Hashimoto T
    • Organizer
      9th World Stroke Congress
    • Place of Presentation
      Istanbul, Turkey
    • Year and Date
      2014-10-22 – 2014-10-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Activation of M2 macrophage in the late phase after cerebral ischemia promotes the expression of neurogenesis related molecules2014

    • Author(s)
      Kurashiki Y, Kitazato K1, Uto Y, Yagi K, Shimada K, Miyamoto T1, Sumiyoshi M, Tada Y, Kuwayama K, Satomi J, Nagahiro S
    • Organizer
      9th World Stroke Congress
    • Place of Presentation
      Istanbul, Turkey
    • Year and Date
      2014-10-22 – 2014-10-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Is the regulation of M1 macrophage activation beneficial in the acute phase of post cerebral ischemia?2014

    • Author(s)
      Kurashiki Y, Kitazato K1, Uto Y, Yagi K, Shimada K, Miyamoto T1, Sumiyoshi M, Tada Y, Kuwayama K, Satomi J, Nagahiro S
    • Organizer
      9th World Stroke Congress
    • Place of Presentation
      Istanbul, Turkey
    • Year and Date
      2014-10-22 – 2014-10-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Hemodynamic changes may elicit the formation and rupture of experimental cerebral aneurysms2014

    • Author(s)
      Miyamoto T, David K. Kung, Korai M, Kitazato KT, Shimada K, Yagi K, Tada Y, Kurashiki Y, Kuwayama K, Satomi J, Nagahiro S
    • Organizer
      9th World Stroke Congress
    • Place of Presentation
      Istanbul, Turkey
    • Year and Date
      2014-10-22 – 2014-10-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Role of angiotensin (1-7) and angiotensin type 2 receptor on intracranial aneurysmal rupture2014

    • Author(s)
      Shimada K, K.Wada, H.Furukawa, Y.Wei, Y.Tada, A.Kuwabara, F.Shikata, K.T.Kitazato, S.Nagahiro, T.Hashimoto
    • Organizer
      9th World Stroke Congress
    • Place of Presentation
      Istanbul, Turkey
    • Year and Date
      2014-10-22 – 2014-10-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Role of angiotensin (1-7) and angiotensin type 2 receptor on intracranial aneurysmal rupture2014

    • Author(s)
      Shimada K, Wada K, Tada Y, Wei Y, Kuwabara A, Shikata F, Furukawa H, Kitazato KT, Nagahiro S, Hashimoto T
    • Organizer
      International Stroke Conference 2014
    • Place of Presentation
      San Diego Convention Center (San Diego, USA)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of hyperhomocysteinemia in the development of intracranial aneurysms2013

    • Author(s)
      Korai M, Kung DK, Kitazato KT, Matsushita N, Tada Y, Yagi K, Shimada K, Kanematsu Y, Satomi J, Nagahiro S
    • Organizer
      Congress of Neurological Surgeons 2013
    • Place of Presentation
      Moscone West Convention Center (San Francisco, USA)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Estrogen protects against aneurysmal rupture through estrogen receptor-beta in ovariectomized mice2013

    • Author(s)
      Yoshiteru Tada, et al.
    • Organizer
      International Stroke Conference 2013
    • Place of Presentation
      ヒルトンハワイアンビレッジ(アメリカ合衆国)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Imbalance between activation of matrix metalloprotease and its inhibition may facilitate2013

    • Author(s)
      Masaaki Kohrai, et al.
    • Organizer
      International Stroke Conference 2013
    • Place of Presentation
      ヒルトンハワイアンビレッジ(アメリカ合衆国)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 卵巣摘出マウスにおいて、エストロゲンはエストロゲン受容体-betaを介して脳動脈瘤破裂を抑制する2013

    • Author(s)
      多田恵曜, 他
    • Organizer
      第38回日本脳卒中学会総会
    • Place of Presentation
      グランドプリンスホテル新高輪(東京都)
    • Related Report
      2012 Annual Research Report
  • [Presentation] The significance of endovascular therapy in vertebral artery dissecting aneurysm2012

    • Author(s)
      Masaaki Kohrai, et al.
    • Organizer
      10th Meeting of Asian Australasian Federation of Interventional and Therapeutic Neuroradiology
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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