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Role of estrogen deficiency in the formation and progression of cerebral aneurysms

Research Project

Project/Area Number 19390381
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionThe University of Tokushima

Principal Investigator

NAGANIRO Shunji  The University of Tokushima, 大学院・ヘルスバイオサイエンス研究部, 教授 (60145315)

Co-Investigator(Kenkyū-buntansha) MATSUBARA Shunji  徳島大学, 医学部・歯学部附属病院, 講師 (60294675)
NISHI Kyoko  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 講師 (60335817)
NAKAJIMA Norio  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (00332817)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2008: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2007: ¥13,780,000 (Direct Cost: ¥10,600,000、Indirect Cost: ¥3,180,000)
Keywords脳動脈瘤 / エストロゲン / 高血圧 / 酸化ストレス / 炎症
Research Abstract

頚動脈脈内膜剥離術の至適な施行時期を解析するため、発症後一週以内の急性期とそれ以後の慢性期に手術により摘出したプラークを免疫組織学的に安定性/不安定性プラークに分類した。さらにプラーク中の酸化LDLおよびマトリックスメタロプロテナーゼー9(MMP-9)の含有量や活性を測定し、免疫組織学的にこれらの局在を調べた。頚動脈狭窄症例の発症早期に酸化LDL含量やMMP-9の活性が、慢性期に摘出したプラークに較べて上昇していることを明らかにした。さらに酸化LDLのマクロファージへの取り込みに関与するプロテオグリカン蛋白発現量およびその局在を評価している。従来頚動脈脈内膜剥離術は症状の安定を待って手術が施行されていた。しかし頚動脈狭窄症例では発症早期により強い酸化ストレスや炎症性変化があることを示した。本研究結果から、発症早期に手術を行うことが妥当であることを示唆した。この所見についてはJournal of Vasoular Surgeryに投稿し、受理された。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report

Research Products

(17 results)

All 2009 2008 2007 Other

All Journal Article Presentation Remarks Patent(Industrial Property Rights)

  • [Journal Article] Edaravone, a free radical scavenger, inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasminogen activator2009

    • Author(s)
      Yagi K, Kitazato KT, Uno M, Tada Y, Kinouchi T, Shimada K, Nagahiro S
    • Journal Title

      Stroke 40

      Pages: 626-631

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Endothelial damage due to impaired NO hioavailability triggers cerebral aneurysm formation in female rats-Endothelial damage and cerebral aneurysm2009

    • Author(s)
      Tamura T, Jamous MA, Kitazato KT, Yagi K, Tada Y, Uno M, Nagahiro S
    • Journal Title

      J Hypertens (掲載予定)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Endothelial damage due to impaired NO bioavailability triggers cerebral aneurysm formation in female rats2009

    • Author(s)
      Tamura T
    • Journal Title

      J Hypertension (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Edaravone, a free radical scavenger, inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasminogen activator2009

    • Author(s)
      Yagi K
    • Journal Title

      Stroke 40

      Pages: 626-631

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protective mechanisms of the angiotensin II type 1 receptor blocker candesartan against cerebral ischemia : in-vivo and in-vitro studies2008

    • Author(s)
      Liu H, Kitazato KT, Uno M, Yagi K, Kanematsu Y, Tamura T, Tada Y, Kinouchi T, Nagahiro S
    • Journal Title

      Journal of Hypertension 26(7)

      Pages: 1435-1445

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protective mechanisms of the angiotensin II type 1 receptor blocker candesartan against cerebral ischemia : in-vivo and in-vitro studies2008

    • Author(s)
      Liu H
    • Journal Title

      Journal of Hypertension 2 6

      Pages: 1435-1445

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endothelial injury and inflammatory response induced by hemodynamic changes preceding intracranial aneurysm formation : experimental study in rats2007

    • Author(s)
      Jamous MA, Nagahiro S, Kitazato KT, Tamura T, Aziz HA, Shone M, Satoh K
    • Journal Title

      J.Neurosurg 107

      Pages: 405-411

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] S.Nagahiro,K.T.Kitazato,T.Tamura,H.A.Aziz,M.Shono,K.Satoh2007

    • Author(s)
      M.A.Jamous
    • Journal Title

      Journal of Neurosurgery 107

      Pages: 405-411

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] WHAT SHOULD WE DO TO PREVENT CEREBRAL ANEURYSM FORMATION AND PROGRESSION ?2008

    • Author(s)
      Nagahiro S
    • Organizer
      6^<th> World Stroke Congress
    • Place of Presentation
      Vienna (Austria)
    • Year and Date
      2008-09-25
    • Related Report
      2008 Annual Research Report
  • [Presentation] Nagahiro S.Down-regulation of tight junction proteins triggers and promotes cerebral aneurysms formation in rats2008

    • Author(s)
      Tada Y, Yagi K, Kitazato KT, Tamura T, Kinouchi T, Nakajima N, Matsubara S, Uno M
    • Organizer
      6^<th> World Stroke Congress
    • Place of Presentation
      Vienna, Austria
    • Related Report
      2008 Final Research Report
  • [Presentation] WHAT SHOULD WE DO TO PREVENT CEREBRAL ANEURYSM FORMATION AND PROGRESSION?2008

    • Author(s)
      Nagahiro S, Tamura T, Yagi K, Tada Y, famous MA, Uno M, Nakajima N, Matsubara S, Kitazato KT.
    • Organizer
      6^<th> World Stroke Congress
    • Place of Presentation
      Vienna, Austria
    • Related Report
      2008 Final Research Report
  • [Presentation] EUKOCYTE ADHESION MOLECULES CONTRIBUTE TO THE DEVELOPMENT OF CEREBRAL ANEURYSMS IN RATS2008

    • Author(s)
      Yagi K, Kitazato KT, Tada Y, Tamura T, Nakajima N, Matsuhara S, Nagahiro S.
    • Organizer
      6^<th> World Stroke Congress
    • Place of Presentation
      Vienna, Austria
    • Related Report
      2008 Final Research Report
  • [Presentation] SYSTEMIC-AND FOCAL EFFECTS OP CANDESARTAN AGAINST CEREBRAL ISCHEMIA2008

    • Author(s)
      Kitazato KT, Uno M, Yagi K, Liu H, Tamura T, Tada Y, Kinouchi T, Shimada K, Nagahiro S.
    • Organizer
      6^<th> World Stroke Congress
    • Place of Presentation
      Vienna, Austria
    • Related Report
      2008 Final Research Report
  • [Presentation] Synergistic effect of hypertension and estrogen deficiency contribute to endothelial dysfunction and increase the risk for cerebral aneurysm formation in rats2007

    • Author(s)
      Tamura T, Kitazato K, Tada Y, Yagi K, Nagahiro S.
    • Organizer
      2007 Congress of Neurological Surgeons Annual Meeting
    • Place of Presentation
      San Diego, USA
    • Related Report
      2008 Final Research Report
  • [Remarks]

    • URL

      http://www.neurosurgerytokushima.com/

    • Related Report
      2008 Annual Research Report
  • [Patent(Industrial Property Rights)] 国際特許2008

    • Inventor(s)
      永廣信治
    • Industrial Property Rights Holder
      下河辺尚史
    • Filing Date
      2008-08-15
    • Related Report
      2008 Annual Research Report
  • [Patent(Industrial Property Rights)] イブジブラストを有効成分とする悩動脈瘤の予防、形成抑制又は治療剤

    • Inventor(s)
      永廣信治・徳島大学・大学院ヘルスバイオサイエンス研究部・教授
    • Industrial Property Rights Holder
      下河辺尚史・杏林製薬株式会社
    • Related Report
      2008 Final Research Report

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Published: 2007-03-31   Modified: 2016-04-21  

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