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Development of a treatment for cerebral microcirculation disorder in early brain injury (EBI) after subarachnoid hemorrhage

Research Project

Project/Area Number 16K19993
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurosurgery
Research InstitutionHirosaki University

Principal Investigator

Naraoka Masato  弘前大学, 医学部附属病院, 講師 (10455751)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsくも膜下出血 / 脳微小循環障害 / 脳血管攣縮 / 遅発性脳虚血 / 早期脳損傷 / 微小循環障害 / 酸化ストレス / 脳神経疾患 / 脳・神経
Outline of Final Research Achievements

A subarachnoid hemorrhage model with rat internal carotid artery perforation was used; SD male rats (400-450 g) were used. Cerebral pressure is continuously monitored before the creation of the subarachnoid hemorrhage. For the rat subarachnoid hemorrhage model, cilostazol, veraprost sodium, and ozagrel sodium groups were created as treatment intervention groups. The cilostazol group showed significant inhibition of cerebral vasospasm and eNOS reduction, inhibition of neuronal apoptosis, and amelioration of microcirculatory disturbances by reducing cerebral edema, while the veraprost sodium and ozagrel sodium groups showed no significant difference.
In view of these results, we decided not to create a duplicate treatment group with cilostazol and investigated the use of apple polyphenol, which has been demonstrated to inhibit oxidative stress, as an additional therapeutic agent, and confirmed the improvement effect of eNOS.

Academic Significance and Societal Importance of the Research Achievements

くも膜下出血は未だに多くの有病率、高い死亡率を伴う出血性脳卒中であり、開頭脳動脈瘤頚部クリッピング術やコイル塞栓術にて脳動脈瘤の根治治療にて一命を取り留めたとしても、その後の脳血管攣縮、遅発性脳虚血などによって重大な後遺症を残す可能性がある。後遺症の克服のため、遅発性脳虚血の原因の一つである脳微小循環障害の治療を目的とした研究を行い、シロスタゾールおよびポリフェノールにて改善の兆しが認められた。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (10 results)

All 2020 2019 2018 2017

All Journal Article (5 results) (of which Peer Reviewed: 4 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Effects of apple polyphenols on oxidative stress and cerebral vasospasm after subarachnoid hemorrhage in a rabbit double hemorrhage model2020

    • Author(s)
      Naraoka Masato、Li Yuchen、Katagai Takeshi、Ohkuma Hiroki
    • Journal Title

      Brain Hemorrhages

      Volume: 1 Issue: 1 Pages: 54-58

    • DOI

      10.1016/j.hest.2019.12.006

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Role of Intracranial Pressure and Subarachnoid Blood Clots in Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats2019

    • Author(s)
      Naraoka Masato、Fumoto Toshio、Li Yuchen、Katagai Takeshi、Ohkuma Hiroki
    • Journal Title

      World Neurosurgery

      Volume: 129 Pages: e63-e72

    • DOI

      10.1016/j.wneu.2019.05.009

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Role of Oxidative Stress in Microvascular Disturbances after Experimental Subarachnoid Hemorrhage2019

    • Author(s)
      Fumoto, Toshio Naraoka, Masato Katagai, Takeshi Li, Yuchen Shimamura, Norihito Ohkuma, Hiroki
    • Journal Title

      Translational Stroke Research

      Volume: 10 Issue: 6 Pages: 684-694

    • DOI

      10.1007/s12975-018-0685-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Effect of Goreisan on the Prevention of Chronic Subdural Hematoma Recurrence: Multi-Center Randomized Controlled Study2018

    • Author(s)
      Katayama Kosuke、Matsuda Naoya、Kakuta Kiyohide、Naraoka Masato、Takemura Atsuhito、Hasegawa Seiko、Akasaka Kenichi、Shimamura Norihito、Itoh Katsuhiro、Asano Kenichiro、Konno Hiromu、Ohkuma Hiroki
    • Journal Title

      Journal of Neurotrauma

      Volume: 35 Issue: 13 Pages: 1537-1542

    • DOI

      10.1089/neu.2017.5407

    • Related Report
      2018 Research-status Report
  • [Journal Article] Long-acting statin for aneurysmal subarachnoid hemorrhage: A randomized, double-blind, placebo-controlled trial2017

    • Author(s)
      Naraoka Masato、Matsuda Naoya、Shimamura Norihito、Asano Kenichiro、Akasaka Kenichi、Takemura Atsuhito、Hasegawa Seiko、Ohkuma Hiroki
    • Journal Title

      Journal of Cerebral Blood Flow & Metabolism

      Volume: 0 Issue: 7 Pages: 1-9

    • DOI

      10.1177/0271678x17724682

    • NAID

      130007655921

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Evaluation of the microcirculatory dysfunction by Arterial Spin Labeling (ASL) after subarachnoid hemorrhage2019

    • Author(s)
      Masato Naraoka
    • Organizer
      ISAH2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脳血管攣縮予防と予後改善への当施設での取り組み2019

    • Author(s)
      奈良岡征都
    • Organizer
      第35回スパズムシンポジウム
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] くも膜下出血後の遅発性脳虚血と予後に対する脳微小循環時間の影響2018

    • Author(s)
      奈良岡征都、松田尚也、片貝武、嶋村則人、大熊洋揮
    • Organizer
      第34回スパズム・シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] くも膜下出血後Early Brain Injuryに対する酸化ストレス抑制の効果2018

    • Author(s)
      奈良岡征都、麓敏雄、松田尚也、片貝武、嶋村則人、大熊洋揮
    • Organizer
      第34回スパズム・シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] くも膜形成による血腫クリアランスの促進とスパズム予防2017

    • Author(s)
      奈良岡征都、松田尚也、片貝武、嶋村則人、大熊洋揮
    • Organizer
      第33回スパズム・シンポジウム
    • Place of Presentation
      大阪国際会議場(大阪府・大阪市)
    • Year and Date
      2017-03-16
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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