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Elucidation of microRNA-mediated signaling in cerebral vasospasm

Research Project

Project/Area Number 17K10848
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, 客員准教授 (80423515)

Co-Investigator(Kenkyū-buntansha) 栗田 浩樹  埼玉医科大学, 医学部, 教授 (70262003)
林 健  埼玉医科大学, 医学部, 教授 (40314679)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords脳血管攣縮 / くも膜下出血 / microRNA
Outline of Final Research Achievements

The aim of this study was to explore the role of microRNA(miR) in the development of cerebral vasospasm following subarachnoid hemorrhage (SAH). Peripheral blood and cerebro-spinal fluid (CSF) samples were collected from SAH patients, and microarray analysis and PCR analysis were performed. miR-15a expression was significantly increased in both the CSF and plasma, with a peak around 3 to 5 days after SAH, whereas the expression of Kruppel-like factor 4 (KLF4) was significantly decreased around 1 to 3 days after SAH and remained lower than in controls. Our results suggest that an early and persistent decrease in KLF4 followed by an increase in miR-15a may contribute to the altered vascular phenotype, resulting in development of cerebral vasospasm.

Academic Significance and Societal Importance of the Research Achievements

近年、血管恒常性維持における様々なmicroRNA(miR)の関与が示唆されているが、脳血管攣縮発症におけるその役割や機能に関しては、ほとんど研究されていない。本研究では、血管新生、血管増殖に関与する可能性があるmiR15aの発現と、miR15aを介して抗増殖、抗血管新生作用を有すると考えられるKLF4の有意な発現変化を明らかにし、これにより、miRによる遺伝子発現制御機構がSAH後の脳血管収縮性変化の獲得に関与している可能性が示唆された。分泌型miRNAが血液や髄液中で安定しして存在していることから、今後、臨床上有用な生物マーカーとなる可能性を秘めている。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (12 results)

All 2020 2019 2018 2017

All Journal Article (8 results) (of which Peer Reviewed: 7 results) Presentation (3 results) (of which Int'l Joint Research: 1 results) Book (1 results)

  • [Journal Article] Clinical Features of Neurogenic Pulmonary Edema in Patients with Subarachnoid Hemorrhage2020

    • Author(s)
      Tatsuki Kimura, Tomoya Kamide, Koki Onodera, Shinya Tabata, Aoto Shibata, Kaima Suzuki, Ririko Takeda, Toshiki Ikeda, Yuichiro Kikkawa, Satoshi Iihoshi, Shinya Kohyama, Hiroki Kurita
    • Journal Title

      World Neurosurg.

      Volume: 135 Pages: e505-e509

    • DOI

      10.1016/j.wneu.2019.12.060

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Predictors of the Resolution of Cavernous Sinus Syndrome Caused by Large/Giant Cavernous Carotid Aneurysms After Parent Artery Occlusion With High-Flow Bypass2019

    • Author(s)
      Yuichiro Kikkawa, Tomomichi Kayahara, Akio Teranishi, Aoto Shibata, Kaima Suzuki, Tomoya Kamide, Toshiki Ikeda, Hiroki Kurita
    • Journal Title

      World Neurosurg.

      Volume: 132 Pages: e637-e644

    • DOI

      10.1016/j.wneu.2019.08.059

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ruptured Intrameatal Anterior Inferior Cerebellar Artery Aneurysm Associated With Obstructed Internal Auditory Artery in a Patient With Sudden Hearing Loss and Vertigo2019

    • Author(s)
      Yuichiro Kikkawa, Kaima Suzuki, Akio Teranishi, Taichi Tachikawa, Hiroki Kurita
    • Journal Title

      Acta Neurochir (Wien)

      Volume: 161(2) Issue: 2 Pages: 403-406

    • DOI

      10.1007/s00701-018-3771-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and neuropathologic analysis of interacerebral hemorrhage in patients with cerebral amyloid angiopathy.2018

    • Author(s)
      Yanagawa T, Takao M, Yasuda M, Kamide T, Sato H, Suzuki K, Ikeda T, Kikkawa Y, Kurita H
    • Journal Title

      Clin Neurol Neurosurg

      Volume: 176 Pages: 110-115

    • DOI

      10.1016/j.clineuro.2018.11.020

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 専門医に求められる最新の知識. 脳血管攣縮の病態と治療: 最新の知見2018

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

      脳神経外科速報

      Volume: 28 (11) Pages: 1100-1107

    • Related Report
      2018 Research-status Report
  • [Journal Article] The dose of direct oral anticoagulants and outcomes of intracerebral hemorrhage: Preliminary findings.2018

    • Author(s)
      Suzuki K, Kato Y, Hayashi T, Maruyama H, Kikkawa Y, Kurita H
    • Journal Title

      Clin Neurol Neurosurg

      Volume: 174 Pages: 63-67

    • DOI

      10.1016/j.clineuro.2018.09.011

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Results of Early High-Flow Bypass and Trapping for Ruptured Blood Blister-Like Aneurysms of the Internal Carotid Artery2017

    • Author(s)
      Kikkawa Y, Ikeda T, Takeda R, Nakajima H, Ogura T, Ooigawa H, Kurita H
    • Journal Title

      World Neurosurg

      Volume: 105 Pages: 470

    • DOI

      10.1016/j.wneu.2017.06.033

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multiple simultaneous intracerebral hemorrhages: Clinical presentations and risk factors2017

    • Author(s)
      Yamaguchi Y, Takeda R, Kikkawa Y, Ikeda T, Suzuki K, Shibata A, Tiezzi G, Araki R, Kurita H
    • Journal Title

      J Neurol Sci

      Volume: 383 Pages: 35

    • DOI

      10.1016/j.jns.2017.10.005

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 破裂脳動脈瘤患者における持続脳槽洗浄と多剤薬物治療によるスパズム予防の治療成績2019

    • Author(s)
      小野寺康輝、吉川雄一郎、田端晋也、松澤良、柴田碧人、吉川信一朗、武田純一、上出智也、池田俊貴、高橋秀寿、神山信也、高尾昌樹、栗田浩樹
    • Organizer
      第35回スパズム・シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] くも膜下出血後の髄液・血液中のmiR15aの発現変化とその役割2018

    • Author(s)
      吉川雄一郎、木村辰規、松澤良、栢原智道、柴田碧人、武田純一、上出智也、池田俊貴、栗田浩樹
    • Organizer
      第61回日本日本脳循環代謝学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Microcirculatory Impairment is Caused by Independent Mechanisms From Major Arterial Spasm Both in the Acute and Chronic Phase After Experimental SAH2018

    • Author(s)
      Kikkawa Y, Kamide T, Uramaru K, Suzuki K, Takeda R, Tsuchiya R, Ikeda R, Shibata A, Kurita H
    • Organizer
      International Stroke Conference 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Book] Neurovascular Events after Subarachnoid Hemorrhage2017

    • Author(s)
      Kikkawa Y et al.: Sasaki T, Ohkuma H, Kanamaru K, Suzuki M (eds):
    • Total Pages
      156
    • Publisher
      NARUNIA Inc
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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