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Development of neuroprotective therapy with selective intra-arterial infusion of cold artificial oxygen carrier

Research Project

Project/Area Number 16K10708
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionHokkaido University

Principal Investigator

Abumiya Takeo  北海道大学, 医学研究院, 客員研究員 (80270726)

Co-Investigator(Kenkyū-buntansha) 小松 晃之  中央大学, 理工学部, 教授 (30298187)
中山 若樹  北海道大学, 医学研究院, 講師 (40421961)
数又 研  北海道大学, 大学病院, 講師 (60634144)
七戸 秀夫  北海道大学, 大学病院, 准教授 (80374479)
寳金 清博  北海道大学, 大学病院, 教授 (90229146)
長内 俊也  北海道大学, 医学研究院, 助教 (90622788)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords脳保護療法 / 人工酸素運搬体 / 冷却灌流 / 脳梗塞 / 虚血再灌流障害 / 虚血再灌流傷害 / 活性酸素 / 脳低温療法
Outline of Final Research Achievements

A combination therapy of regional cold perfusion and HBOC administration was performed with a core-shell structured hemoglobin-albumin cluster “HemoAct” in rat transient middle cerebral artery occlusion model. The combination therapy was evaluated in comparison with a monotherapy of regional cold perfusion or HemoAct administration and an untreated control. In analysis of rats with 2-hour ischemia/24-hour reperfusion, combination therapy tended to be less in rCBF reduction and infarct volume. Durability of therapeutic effects of the combination therapy was confirmed till 7days after the treatment. Furthermore, the combination therapy ameliorated neurological disabilities and hemorrhagic transformation in rats with 4-hour and 5-hour ischemia/24-hour reperfusion. Because the therapeutic effects can be expected until 5 hours of ischemia and reperfusion, this therapy is a promising neuroprotective strategy in treatment of acute ischemic stroke.

Academic Significance and Societal Importance of the Research Achievements

主幹動脈閉塞を伴う急性期重症脳梗塞においては血管内血栓除去治療が積極的に行われている。しかし、再開通が得られても虚血再灌流傷害によって著明な脳浮腫、出血性梗塞を来し、予後不良となるケースは少なくない。このため、虚血再灌流傷害を防ぐための脳保護療法の開発は重要な課題といえる。今回、我々が行った冷却した人工酸素運搬体HemoActの投与は虚血時間5時間後の投与においても脳保護効果を発揮したことより、今後の脳梗塞治療においてtherapeutic time windowを拡大する有効な治療法となる可能性が考えられた。

Report

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

    (8 results)

All 2019 2018 2017 2016

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Novel Hemoglobin-Based Oxygen Carrier Bound With Albumin Shows Neuroprotection With Possible Antioxidant Effects2018

    • Author(s)
      Gekka Masayuki、Abumiya Takeo、Komatsu Teruyuki、Funaki Ryosuke、Kurisu Kota、Shimbo Daisuke、Kawabori Masato、Osanai Toshiya、Nakayama Naoki、Kazumata Ken、Houkin Kiyohiro
    • Journal Title

      Stroke

      Volume: 49 Issue: 8 Pages: 1960-1968

    • DOI

      10.1161/strokeaha.118.021467

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] 脳虚血再灌流傷害急性期微小循環障害に対するヘモグロビン‐アルブミン複合型人工酸素運搬体HemoActの効果の検討2019

    • Author(s)
      [演者] 月花 正幸: [共同演者]鐙谷 武雄, 小松晃之、舟木亮佑、栗栖宏多、新保大輔、伊藤 康裕::, 中山 若樹:, 数又 研:, 寳金 清博:
    • Organizer
      第44回日本脳卒中学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脳虚血再灌流傷害に対するアルブミン結合型人工酸素運搬体HemoActの脳保護効果の作用機序―微小循環・酸素運搬能改善と抗酸化作用―2018

    • Author(s)
      [演者] 鐙谷 武雄: [共同演者] 月花 正幸, 伊藤 康裕:, 川堀 真人:, 長内 俊也:, 中山 若樹:, 数又 研:, 寳金 清博:
    • Organizer
      日本脳神経外科学会 第77回学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 人工酸素運搬体HemoActを用いた脳虚血再灌流障害に対する脳保護療法2017

    • Author(s)
      月花 正幸, 鐙谷 武雄, 小松 晃之, 船木 亮佑, 栗栖 宏太, 中山 若樹, 数又 研, 宝金 清博
    • Organizer
      第42回日本脳卒中学会学術集会
    • 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
  • [Presentation] Neuroprotective Therapy for Ischemia-Reperfusion Injury by Hemoglobin-albumin-cluster (HemoAct)2017

    • Author(s)
      Masayuki Gekka, Takeo Abumiya, Teruyuki Komatsu, Ryousuke Funaki, Kota Kurisu, Naoki Nakayama, Ken Kazumata, Hideo Shichinohe and Kiyohiro Houkin
    • Organizer
      International Stroke Conference 2017
    • Place of Presentation
      George R Brown Convention Center, Houston, USA
    • Year and Date
      2017-02-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新規人工酸素運搬体“HemoAct”を用いた脳虚血再灌流治療の開発2017

    • Author(s)
      月花正幸 鐙谷武雄 小松晃之 船木亮佑 栗栖宏多 中山若樹 数又研 宝金清博
    • Organizer
      日本脳神経外学会第76回学術総会
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 虚血性疾患の治療薬2016

    • Inventor(s)
      中央大学、北海道大学
    • Industrial Property Rights Holder
      中央大学、北海道大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016
    • Related Report
      2017 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] 虚血性疾患の治療薬2016

    • Inventor(s)
      小松晃之
    • Industrial Property Rights Holder
      小松晃之
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-07-06
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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