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Development of systemic management after subarachnoid hemorrhage focusing on cerebral microcirculation

Research Project

Project/Area Number 15K10966
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Emergency medicine
Research InstitutionTohoku University

Principal Investigator

Mutoh Tatsushi  東北大学, 加齢医学研究所, 准教授 (80462472)

Research Collaborator TAKI yasuyuki  東北大学, 加齢医学研究所, 教授 (10375115)
TSUBONE hirokazu  東京大学, 農学生命科学研究科, 特任教授 (30142095)
ISHIKAWA tatsuya  秋田県立脳血管研究センター, 脳神経外科学研究部, 部長 (10281809)
NAKAMURA kazuhiro  秋田県立脳血管研究センター, 放射線医学研究部, 主任研究員 (10312638)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsくも膜下出血 / 遅発性脳虚血 / 微小脳循環障害 / 動物モデル / 微小脳循環 / 脳血管攣縮 / 微小循環障害
Outline of Final Research Achievements

Early brain injury and related cardiac consequences play a key role in the devastating outcomes after subarachnoid hemorrhage (SAH). We aimed to evaluate the feasibility of multimodality imaging using MRI, two-photon laser scanning microscopy, high-frequency power Doppler ultrasound imaging in a mouse model of subarachnoid hemorrhage (SAH). Real-time measurements of cerebral blood flow, brain tissue oxygen saturation, and cardiac output (CO) were analyzed. Our in vivo experiments further demonstrated the potential role of the transcription factor STAT3 in the rapamycin-mediated neuroprotection in a mouse model of SAH. We propose that rapamycin is a novel pharmacological strategy to target STAT3 activation for the treatment of post-SAH early brain injury.

Academic Significance and Societal Importance of the Research Achievements

本研究では、くも膜下出血後の超急性期の脳循環障害と心機能障害を生体イメージングによりneurovascular unitから全脳レベルに至るまで可視化することができた。従来のドブタミンによるhyperdynamic療法が微小循環改善において一定の治療効果があることを証明した。さらにmTOR阻害薬ラパマイシンの中枢性効果をin vivoで明らかにすることができた。さらに当初の研究計画の進捗とそれを踏まえた新たな研究の必要性から、本研究の早期完了と新規課題(18K08880 高齢者くも膜下出血の超急性期病態と認知機能に着目した神経集中治療法の開発)への移行に至った。

Report

(4 results)
  • 2018 Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (14 results)

All 2018 2017 2016 2015

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Acknowledgement Compliant: 4 results) Presentation (5 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Reduced CBF recovery detected by longitudinal 3D-SSP SPECT analyses predicts outcome of postoperative patients after subarachnoid haemorrhage2018

    • Author(s)
      Mutoh T, Totsune T, Takenaka S, Tatewaki Y, Nakagawa M, Suarez JI, Taki Y, Ishikawa T
    • Journal Title

      Clin Exp Pharmacol Physiol

      Volume: 45 Issue: 2 Pages: 127-132

    • DOI

      10.1111/1440-1681.12867

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Acute cardiac support with intravenous milrinone promotes recovery from early brain injury in a murine model of severe subarachnoid haemorrhage2017

    • Author(s)
      Mutoh T, Mutoh T, Nakamura K, Yamamoto Y, Tsuru Y, Tsubone H, Ishikawa T, Taki Y
    • Journal Title

      Clin Exp Pharmacol Physiol

      Volume: 44 Issue: 4 Pages: 463-469

    • DOI

      10.1111/1440-1681.12718

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inotropic support against early brain injury improves cerebral hypoperfusion and outcomes in a murine model of subarachnoid hemorrhage2017

    • Author(s)
      Mutoh T, Mutoh T, Nakamura K, Sasaki K, Tatewaki Y, Ishikawa T, Taki Y
    • Journal Title

      Brain Res Bull

      Volume: 130 Pages: 18-26

    • DOI

      10.1016/j.brainresbull.2016.12.009

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neurocardiac protection with milrinone for restoring acute cerebral hypoperfusion and delayed ischemic injury after experimental subarachnoid hemorrhage2017

    • Author(s)
      Mutoh T, Mutoh T, Sasaki K, Nakamura K, Tatewaki Y, Ishikawa T, Taki Y
    • Journal Title

      Neurosci Lett

      Volume: 640 Pages: 70-75

    • DOI

      10.1016/j.neulet.2017.01.008

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] MRI-based in vivo assessment of early cerebral infarction in a mouse filament perforation model of subarachnoid hemorrhage2017

    • Author(s)
      Sasaki K, Mutoh T, Nakamura K, Kojima I, Taki Y, Suarez JI, Ishikawa T
    • Journal Title

      Neurosci Lett

      Volume: 653 Pages: 173-176

    • DOI

      10.1016/j.neulet.2017.05.047

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Isoflurane postconditioning with cardiac support promotes recovery from early brain injury in mice after severe subarachnoid hemorrhage2016

    • Author(s)
      Mutoh T, Mutoh T, Sasaki K, Yamamoto Y, Tsuru Y, Tsubone H, Ishikawa T, Taki Y
    • Journal Title

      Life Sci

      Volume: 153 Pages: 35-40

    • DOI

      10.1016/j.lfs.2016.04.020

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Therapeutic potential of natural product-based oral nanomedicines for stroke prevention2016

    • Author(s)
      Mutoh T, Mutoh T, Taki Y, Ishikawa T
    • Journal Title

      J Med Food

      Volume: 19 Issue: 6 Pages: 521-527

    • DOI

      10.1089/jmf.2015.3644

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Value of three-dimensional maximum intensity projection display to assist in magnetic resonance imaging (MRI)-based grading in a mouse model of subarachnoid hemorrhage.2016

    • Author(s)
      Mutoh T, Mutoh T, Sasaki K, Nakamura K, Taki Y, Ishikawa T
    • Journal Title

      Med Sci Monit

      Volume: 22 Pages: 2050-2055

    • DOI

      10.12659/msm.896499

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 52)Value of three-dimentional maximum intensity projection display to assist in MRI-based grading in a mouse model of subarachnoid hemorrhage2016

    • Author(s)
      Mutoh T, Mutoh T, Sasaki K, Nakamura K, Taki Y, Ishikawa T
    • Journal Title

      Medical Science Monitor

      Volume: 22

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] くも膜下出血の循環管理における低侵襲連続心拍出量モニター(PCCO)の有用性2017

    • Author(s)
      武藤達士, 石川達哉, 瀧 靖之
    • Organizer
      STROKE 2017 第33回スパズム・シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] Detection of early brain injury and risk for DCI using 3D-SSP CBF analysis in patients after SAH2017

    • Author(s)
      Mutoh T, Sasaki K, Mutoh T, Taki Y, Ishikawa T
    • Organizer
      SCCM 46th Critical Care Congress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MRI-based non-invasive assessment of early brain injury and CBF for functional grading of experimental subarachnoid hemorrhage in mice2016

    • Author(s)
      Sasaki K, Nakamura K, Mutoh T, Kawashima R, Ishikawa T, Mutoh T
    • Organizer
      International Stroke Conference 2016
    • Place of Presentation
      Los Angeles, CA, USA
    • Year and Date
      2016-02-10
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] くも膜下出血モデル動物に関するMRI画像評価方法の検討2015

    • Author(s)
      中村和浩, 武藤達士, 佐々木一益, 瀧 靖之, 石川達哉
    • Organizer
      第27回日本脳循環代謝学会総会
    • Place of Presentation
      富山県富山市
    • Year and Date
      2015-10-30
    • Related Report
      2015 Research-status Report
  • [Presentation] くも膜下出血モデル動物に関する行動評価指標の検討2015

    • Author(s)
      中村和浩, 武藤達士, 佐々木一益, 瀧 靖之, 石川達哉
    • Organizer
      第14回情報科学技術フォーラム(FIT2015)
    • Place of Presentation
      愛媛県松山市
    • Year and Date
      2015-09-15
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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