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Elucidation of novel molecular mechanisms underlying the development of cerebral vasospasm after subarachnoid hemorrhage and searching for biomarkers of vasospasm

Research Project

Project/Area Number 26462164
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionSaitama Medical University

Principal Investigator

Kikkawa Yuichiro  埼玉医科大学, 医学部, 准教授 (80423515)

Co-Investigator(Kenkyū-buntansha) 溝口 昌弘  九州大学, 医学研究院, 共同研究員 (50380621)
天野 敏之  九州大学, 医学研究院, 共同研究員 (70448413)
中溝 玲  九州大学, 医学研究院, 共同研究員 (80529800)
栗田 浩樹  埼玉医科大学, 医学部, 教授 (70262003)
竹田 理々子  埼玉医科大学, 医学部, 講師 (70649847)
池田 俊貴  埼玉医科大学, 医学部, 講師 (90406968)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsくも膜下出血 / 脳血管攣縮 / 血管平滑筋収縮 / 血管リモデリング / バイオマーカー
Outline of Final Research Achievements

Cerebral vasospasm after subarachnoid hemorrhage (SAH) is characterized by delayed and prolonged contraction of cerebral arteries, which causes cerebral ischemia, thereby determining the prognosis of both life and neurologic function of SAH patients. The molecular mechanisms of cerebral vasospasm remain to be elucidated. In this study, we investigated the roles of several molecules including relaxin, TIMP-1 and MMP9, which were revealed to be upregulated in the rabbit basilar artery after SAH by microarray analysis, in increased vascular contractility after SAH. As a result, it is suggested that down-regulation of relaxin receptor expression and impaired TIMP-1/MMP9 balance contribute to acquiring persistency of vascular smooth muscle contraction and enhancement of vascular remodeling after SAH, respectively.

Report

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

    (37 results)

All 2017 2016 2015 2014 Other

All Journal Article (13 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 12 results,  Acknowledgement Compliant: 6 results) Presentation (21 results) (of which Int'l Joint Research: 7 results,  Invited: 2 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Oculomotor Nerve Palsy in a Patient with a Ruptured Middle Cerebral Artery Aneurysm2017

    • Author(s)
      Yokosako S, Kikkawa Y, Takeda R, Ikeda T, Kurita H.
    • Journal Title

      The Journal of Medical Investigation

      Volume: 64 Issue: 1.2 Pages: 165-167

    • DOI

      10.2152/jmi.64.165

    • NAID

      130005501974

    • ISSN
      1343-1420, 1349-6867
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 破裂血豆状内頚動脈前壁動脈瘤に対する急性期high-flow bypass併用動脈瘤trapping術の治療成績2017

    • Author(s)
      吉川雄一郎、池田俊貴、竹田理々子、中島弘之、大井川秀聡、栗田浩樹
    • Journal Title

      脳卒中の外科

      Volume: 45 (3) Pages: 15-17

    • NAID

      130005712191

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 当施設における破裂脳動脈瘤に対する脳血管攣縮期を含む非急性期の開頭手術の成績2016

    • Author(s)
      佐藤大樹、吉川雄一郎、武裕士郎、大熊理弘、中島弘之、竹田理々子、柳川太郎、鈴木海馬、池田俊貴、栗田浩樹:
    • Journal Title

      脳血管攣縮

      Volume: 32 Pages: 31-35

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 当施設におけるくも膜下出血開頭手術患者の術後経過における年齢因子の関与2016

    • Author(s)
      吉川雄一郎、大熊理弘、佐藤大樹、柳川太郎、鈴木海馬、浦丸浩一、中島弘之、池田俊貴、竹田理々子、栗田浩樹
    • Journal Title

      脳血管攣縮

      Volume: 32 Pages: 10-13

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] スパズム期の看護 (特集 スパズム期の治療と看護)2016

    • Author(s)
      吉川雄一郎
    • Journal Title

      BRAIN NURSING

      Volume: 32 (8) Pages: 92-95

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Ruptured posterior spinal artery aneurysm: Intraoperative and histologic findings with appreciable thrombosis2016

    • Author(s)
      Ikeda S, Takai K, Kikkawa Y, Takeda R, Ikeda T, Kohyama S, Kurita H.
    • Journal Title

      Spine J

      Volume: 16 Issue: 3 Pages: e215-e217

    • DOI

      10.1016/j.spinee.2015.11.015

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Mechanisms underlying increased vascular smooth muscle contractility in the rabbit basilar artery following subarachnoid hemorrhage2015

    • Author(s)
      Kikkawa Y, Kameda K, Matsuo S, Kurogi R, Nakamizo A, Mizoguchi M, Sasaki T
    • Journal Title

      Acta Neurochir Suppl

      Volume: 120 Pages: 95-98

    • DOI

      10.1007/978-3-319-04981-6_16

    • ISBN
      9783319049809, 9783319049816
    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A rabbit cisterna magna double-injection subarachnoid hemorrhage model2015

    • Author(s)
      Kikkawa Y
    • Journal Title

      Acta Neurochir Suppl

      Volume: 120 Pages: 331-335

    • DOI

      10.1007/978-3-319-04981-6_57

    • ISBN
      9783319049809, 9783319049816
    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The single and double blood injection rabbit subarachnoid hemorrhage model.2015

    • Author(s)
      Kikkawa Y, Kurogi R, Sasaki T
    • Journal Title

      Transl Stroke Res.

      Volume: 6(1) Issue: 1 Pages: 88-97

    • DOI

      10.1007/s12975-014-0375-5

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Upregulation of tissue inhibitor of metalloproteinase-1 contributes to restration of the extracellular matrix in the rabbit basilar artery during vasospasm after subarachnoid hemorrhage.2015

    • Author(s)
      Kurogi R, Kikkawa Y, Matsuo S, Nakamizo A, Mizoguchi M, Sasaki T
    • Journal Title

      Brain Res

      Volume: 1616 Pages: 26-36

    • DOI

      10.1016/j.brainres.2015.04.049

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Hyperperfusion syndrome after aneurysm surgery: a case report2015

    • Author(s)
      Kayahara T, Takeda R, Kikkawa Y, Take Y, Kurita H
    • Journal Title

      Acta Neurochir (Wien).

      Volume: 157 Issue: 11 Pages: 1855

    • DOI

      10.1007/s00701-015-2567-5

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] くも膜下出血急性期のclipping:現状と展望.2015

    • Author(s)
      吉川雄一郎、池田俊貴、中島弘之、山口陽平、竹田理々子、小倉丈司、大井川秀聡、栗田浩樹
    • Journal Title

      Neurosurg Emerg

      Volume: 20 Pages: 45-48

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 当施設におけるくも膜下出血開頭術後患者の周術期管理と治療成績.2015

    • Author(s)
      吉川雄一郎、池田俊貴、中島弘之、山口陽平、竹田理々子、小倉丈司、大井川秀聡、栗田浩樹
    • Journal Title

      脳血管攣縮

      Volume: 31 Pages: 21-25

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Analyses of CSF and serum miRNA expression in SAH patients suggest important roles in restoration of impaired vascular homeostasis after SAH.2017

    • Author(s)
      Kikkawa Y, Uramaru K, Sato H, Yanagawa T, Suzuki K, Okuma M, Nakajima H, Takeda R, Kurita H
    • Organizer
      International Stroke Conference 2017
    • Place of Presentation
      Houston, USA
    • Year and Date
      2017-02-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Acute catecholamine surge in patients with aneurysmal subarachnoid hemorrhage: Characteristics and prognostic value.2017

    • Author(s)
      Uramaru K, Kikkawa Y, Sato H, Yanagawa T, Suzuki K, Okuma M, Nakajima H, Takeda R, Kurita H
    • Organizer
      International Stroke Conference 2017
    • Place of Presentation
      Houston, USA
    • Year and Date
      2017-02-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脳血管攣縮の発症メカニズムに関する研究2017

    • Author(s)
      吉川雄一郎
    • Organizer
      第4回Clinical Science Forum
    • Place of Presentation
      埼玉、日本
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 当施設におけるくも膜下出血開頭手術患者の術後経過における年齢因子の関与2016

    • Author(s)
      吉川雄一郎、池田俊貴、竹田理々子、大熊理弘、伊藤清佳、武裕士郎、柳川太郎、佐藤大樹、鈴木海馬、栗田浩樹
    • Organizer
      STROKE2016
    • Place of Presentation
      札幌
    • Year and Date
      2016-04-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] 当施設における破裂脳動脈瘤に対するスパズム期を含む非急性期における開頭手術2016

    • Author(s)
      佐藤大樹、吉川雄一郎、武裕士郎、大熊理弘、伊藤清佳、竹田理々子、柳川太郎、鈴木海馬、池田俊貴、栗田浩樹
    • Organizer
      STROKE2016
    • Place of Presentation
      札幌
    • Year and Date
      2016-04-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] 当施設における破裂内頸動脈前壁動脈瘤に対する急性期内頸動脈trapping・高流量バイパス術.2015

    • Author(s)
      吉川雄一郎、池田俊貴、竹田理々子、中島弘之、山口陽平、伊藤清佳、下吹越航、池上方基、寺西亮雄、大井川秀聡、栗田浩樹
    • Organizer
      第74回日本脳神経外科学会学術総会
    • Place of Presentation
      ロイトン札幌(札幌市、北海道)
    • Year and Date
      2015-10-14
    • Related Report
      2015 Research-status Report
  • [Presentation] Mechanisms underlying increased vascular contractivity after subarachnoid hemorrhage.2015

    • Author(s)
      Kikkawa Y
    • Organizer
      13th International Symposium on Neurovascular Events after Subarachnoid Hemorrhage (Vasospasm 2015)
    • Place of Presentation
      軽井沢プリンスホテル(軽井沢町、長野県)
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Management and clinical outcome of aneurismal subarachnoid hemorrhage with surgery in Saitama Medical University International Medical Center.2015

    • Author(s)
      Kikkawa Y, Ooigawa H, Ikeda T, Nakajima H, Yamaguchi Y, Ito S, Shimohigoshi W, Teranishi A, Ikegami M, Kurita H
    • Organizer
      13th International Symposium on Neurovascular Events after Subarachnoid Hemorrhage (Vasospasm 2015)
    • Place of Presentation
      軽井沢プリンスホテル(軽井沢町、長野県)
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] : A case of reversible central auditory dysfunction caused by cerebral vasospasm following traumatic subarachnoid hemorrhage.2015

    • Author(s)
      Shimohigoshi W, Kikkawa Y, Ikeda T, Nakajima H, Yamaguchi Y, Ito S, Teranishi A, Ikegami M, Kurita H
    • Organizer
      13th International Symposium on Neurovascular Events after Subarachnoid Hemorrhage (Vasospasm 2015)
    • Place of Presentation
      軽井沢プリンスホテル(軽井沢町、長野県)
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Upregulation of relaxin after experimental subarachnoid hemorrhage.2015

    • Author(s)
      Kikkawa Y, Matsuo S, Kurogi R, Takeda R, Ikeda T, Yamaguchi Y, Nakajima H, Ogura T, Ooigawa H, Kurita H
    • Organizer
      14th Asian Australasian Congress of Neurological Surgeons (AACNS)
    • Place of Presentation
      Jeju Island, Korea
    • Year and Date
      2015-04-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Chronological change of vasospsm and microcirculatory disturbance after experimental ubarachnoid hemorrhage.2015

    • Author(s)
      Kikkawa Y, Kurogi R, Matsuo S, Takeda R, Ikeda T, Yamaguchi Y, Nakajima H, Ogura T, Ooigawa H, Kurita H
    • Organizer
      14th Asian Australasian Congress of Neurological Surgeons (AACNS)
    • Place of Presentation
      Jeju Island, Korea
    • Year and Date
      2015-04-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 当施設におけるくも膜下出血開頭術後患者の周術期管理と治療成績2015

    • Author(s)
      吉川雄一郎、竹田理々子、池田俊貴、伏原豪司、栢原智道、山口陽平、横佐古卓、上野龍、大井川秀聡、栗田浩樹:
    • Organizer
      Stroke2015
    • Place of Presentation
      広島
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] クモ膜下出血後の脳血管攣縮―そのメカニズムと当科における取り組みー.2015

    • Author(s)
      吉川雄一郎
    • Organizer
      埼玉西部脳循環懇話会
    • Place of Presentation
      日高
    • Year and Date
      2015-03-03
    • Related Report
      2014 Research-status Report
  • [Presentation] Correlation between vasospasm and microcirculatory disturbance in early and delayed phase following experimental subarachnoid hemorrhage.2015

    • Author(s)
      Kikkawa Y, Kurogi R, Matsuo S, Mizoguchi M, Kayahara T, Yokosako S, Ueno R, Yamaguchi Y, Fushihara G, Ikeda T, Takeda R, Ogura T, Ooigawa H, Sasaki T, Kurita H:
    • Organizer
      International Stroke Conference 2015
    • Place of Presentation
      Nashville, USA
    • Year and Date
      2015-02-11 – 2015-02-13
    • Related Report
      2014 Research-status Report
  • [Presentation] Upregulation of relaxin after experimental subarachnoid hemorrhage2015

    • Author(s)
      Kikkawa Y, Matsuo S, Kurogi R, Mizoguchi M, Kayahara T, Yokosako S, Ueno R, Yamaguchi Y, Fushihara G, Ikeda T, Takeda R, Ogura T, Ooigawa H, Sasaki T, Kurita H:
    • Organizer
      International Stroke Conference 2015
    • Place of Presentation
      Nashville, USA
    • Year and Date
      2015-02-11 – 2015-02-13
    • Related Report
      2014 Research-status Report
  • [Presentation] くも膜下出血患者の周術期管理―当科におけるスパズム予防とその基礎的背景2014

    • Author(s)
      吉川雄一郎、大井川秀聡、栢原智道、横佐古卓、上野龍、山口陽平、伏原豪司、池田俊貴、竹田理々子、小倉丈司、栗田浩樹
    • Organizer
      第8回埼玉ブレインセミナー
    • Place of Presentation
      深谷
    • Year and Date
      2014-11-07
    • Related Report
      2014 Research-status Report
  • [Presentation] Correlation between cerebral vasospasm and microcirculatory disturbance in early and delayed phase after experimental subarachnoiod hemorrhage.2014

    • Author(s)
      Kikkawa Y, Kurogi Y, Matsuo S, Nakamizo A, MIzoguchi M, Take Y, Kayahara T, Yokosako S, Ueno R, Yamaguchi Y, Fushihara G, Ikeda T, Takeda R, Ogura T, Ooigawa H, Kurita H
    • Organizer
      15th European Congress of Neurosurgery
    • Place of Presentation
      Plague, Czech Republic
    • Year and Date
      2014-10-12 – 2014-10-17
    • Related Report
      2014 Research-status Report
  • [Presentation] Role of relaxin in the development of cerebral vasospasm after subarachnoid hemorrhage.2014

    • Author(s)
      Kikkawa Y, Matsuo S, Kurogi Y, Nakamizo A, MIzoguchi M, Take Y, Kayahara T, Yokosako S, Ueno R, Yamaguchi Y, Fushihara G, Ikeda T, Takeda R, Ogura T, Ooigawa H, Kurita H
    • Organizer
      15th European Congress of Neurosurgery
    • Place of Presentation
      Plague, Czech Republic
    • Year and Date
      2014-10-12 – 2014-10-17
    • Related Report
      2014 Research-status Report
  • [Presentation] くも膜下出血後の脳微小循環障害と主幹動脈狭窄の経時的推移―ウサギSAHモデルによる検討2014

    • Author(s)
      吉川雄一郎、黒木亮太、松尾諭、伏原豪司、池田俊貴、竹田理々子、小倉丈司、大井川秀聡、栗田浩樹
    • Organizer
      第73回日本脳神経外科学会学術総会
    • Place of Presentation
      品川
    • Year and Date
      2014-10-09 – 2014-10-11
    • Related Report
      2014 Research-status Report
  • [Presentation] Modern management of aneurymal subarachnoid hemorrhage and cerebral vasospasm2014

    • Author(s)
      Kikkawa Y, Takeda R, Ikeda T, Fushihara G, Yamaguchi Y, Ueno R, Yokosako S, Kayahara T, Take Y, Ooigawa H, Kurita H
    • Organizer
      The 12th Korean and Japanese Friendship Conference on Surgery for Cerebral Stroke
    • Place of Presentation
      大阪
    • Year and Date
      2014-09-26 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] くも膜下出血後の脳微小循環障害とスパスムの経時的変化:ウサギモデルによるMDCTを用いた検討2014

    • Author(s)
      吉川雄一郎、黒木亮太、松尾諭、伏原豪司、池田俊貴、竹田理々子、小倉丈司、大井川秀聡、栗田浩樹
    • Organizer
      第33回 The Mt. Fuji Workshop on CVD
    • Place of Presentation
      盛岡
    • Year and Date
      2014-08-30
    • Related Report
      2014 Research-status Report
  • [Book] Neurovascular Events after Subarachnoid Hemorrhage2017

    • Author(s)
      Kikkawa Y
    • Total Pages
      158
    • Publisher
      NARUNIA Inc
    • Related Report
      2016 Annual Research Report
  • [Book] Neurovascular Events after Subarachnoid Hemorrhage2017

    • Author(s)
      Kikkawa Y, Ooigawa H, Ikeda T, Takeda R, Nakajima H, Ogura T, Kurita H
    • Total Pages
      158
    • Publisher
      NARUNIA Inc
    • Related Report
      2016 Annual Research Report
  • [Remarks] 埼玉医科大学国際医療センター/脳卒中外科

    • URL

      http://www.saitama-med.ac.jp/kokusai/division_info/72.html#message

    • Related Report
      2015 Research-status Report

URL: 

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

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