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Establishment of novel prophylaxis/treatment for cerebral infarction using SIRT1 activator

Research Project

Project/Area Number 26640034
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Nerve anatomy/Neuropathology
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

Hattori Yorito  国立研究開発法人国立循環器病研究センター, 病院, 客員研究員 (60713849)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsSIRT1 / 頸動脈狭窄症 / 血管性認知症 / 脳血流量 / 脳低還流 / 脳虚血 / 内皮型一酸化窒素合成酵素 / 脱アセチル化
Outline of Final Research Achievements

We hypothesized that SIRT1 counertacts cerebral ischemia/hypoperfusion.
We did the bilateral common carotid artery stenosis (BCAS) surgery to Sirt1 transgenic (Sirt1-Tg) mice and wild-type (WT) littermates, which induces chronic cerebral hypoperfusion. WT mice showed working memory impairment and cerebral white matter ischemic injury, but Sirt1-Tg mice preserved memory function and cerebral histologic integrity at 1 month after BCAS. For Sirt1-Tg mice showed continuously preserved cerebral blood flow after BCAS even though CBF of WT mice decreased to 70-80% of baseline after the surgery. The mechanism is that SIRT1 deacetylate endothelial nitric oxide synthase (eNOS) and activated that so that cerebral arteries dilate.
We are going to try the clinical research using SIRT1 activator.

Report

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

    (7 results)

All 2016 2015 2014

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (3 results) (of which Int'l Joint Research: 1 results) Book (1 results)

  • [Journal Article] Gradual Carotid Artery Stenosis in Mice Closely Replicates Hypoperfusive Vascular Dementia in Humans.2016

    • Author(s)
      Hattori Y, Enmi J, Iguchi S, Saito S, Yamamoto Y, Tsuji M, Nagatsuka K, Kalaria RN, Iida H, Ihara M
    • Journal Title

      Journal of the American Heart Association

      Volume: 5 Issue: 2

    • DOI

      10.1161/jaha.115.002757

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] SIRT1 attenuates severe ischemic damage by preserving cerebral blood flow.2015

    • Author(s)
      Hattori Y, Okamoto Y, Nagatsuka K, Takahashi R, Kalaria RN, Kinoshita M, Ihara M
    • Journal Title

      NeuroReport

      Volume: 26 Issue: 3 Pages: 113-117

    • DOI

      10.1097/wnr.0000000000000308

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Silent Information Regulator 2 Homolog 1 Counters Cerebral Hypoperfusion Injury by Deacetylating Endothelial Nitric Oxide Synthase2014

    • Author(s)
      Hattori Y, Okamoto Y, Maki T, Yamamoto Y, Oishi N, Yamahara K, Nagatsuka K, Takahashi R, Kalaria RN, Fukuyama H, Kinoshita M, Ihara M
    • Journal Title

      Stroke

      Volume: 45 Issue: 11 Pages: 3403-3411

    • DOI

      10.1161/strokeaha.114.006265

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Gradual Carotid Artery Stenosis in Mice Closely Replicates Hypoperfusive Vascular Dementia in Humans2016

    • Author(s)
      Hattori Y, Enmi J, Okamoto Y, Nagatsuka K, Kalaria RN, Iida H, Ihara M
    • Organizer
      International Stroke Conference 2016
    • Place of Presentation
      Los Angeles
    • Year and Date
      2016-02-16
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 緩徐進行性の脳血流低下による血管性認知障害モデルマウスの作製2015

    • Author(s)
      服部頼都,圓見純一郎,長束一行,飯田秀博,猪原匡史
    • Organizer
      第27回日本脳循環代謝学会総会
    • Place of Presentation
      富山
    • Year and Date
      2015-10-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] A POTENT PROTECTIVE ROLE OF SIRT1 AGAINST CHRONIC CEREBRAL HYPOPERFUSION2014

    • Author(s)
      Hattori Y, Okamoto Y, Yamamoto Y, Oishi N, Nagatsuka K, Takahashi R, Fukuyama H, Kinoshita M, Ihara M
    • Organizer
      第55回日本神経学会学術集会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2014-05-21 – 2014-05-24
    • Related Report
      2014 Research-status Report
  • [Book] 脳卒中―新時代の治療を求めて「SIRT1」2016

    • Author(s)
      服部頼都,猪原匡史
    • Total Pages
      6
    • Publisher
      日本臨牀
    • Related Report
      2015 Annual Research Report

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Published: 2014-04-04   Modified: 2017-05-10  

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