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Novel ischemic therapy targetting post-free radical molecules

Research Project

Project/Area Number 18K08955
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionKurume University

Principal Investigator

Morioka Motohiro  久留米大学, 医学部, 教授 (20295140)

Co-Investigator(Kenkyū-buntansha) 広畑 優  久留米大学, 医学部, 教授 (40218863)
折戸 公彦  久留米大学, 医学部, 講師 (50597408)
吉富 宗健  久留米大学, 医学部, 助教 (80529462)
青木 孝親  久留米大学, 医学部, 講師 (70330842)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords脳梗塞 / 神経細胞障害 / 活性酸素 / 脳虚血 / フリーラジカル / ヒドロキシノネナール / カルノシンヒドラジド / 神経細胞死 / HSP70 / 海馬 / ichemia / therapy / free radical / hydroxy nonenal
Outline of Final Research Achievements

4-hydroxy-trans-2-nonenal (4-HNE), a highly cytotoxic aldehyde, which is produced by peroxide lipid oxidation, induces neuronal cell death in the ischemic disease. We synthesized a novel 4-HNE scavenger; a carnosine-hydrazide derivative, L-carnosine hydrazide (CNN). We examined the anti-ischemic effect of CNN in various models. This compound completely inhibited 4-HNE induced cell toxicity in cultured neuronal cells. In animal models, CNN protected hippocampal CA1 pyramidal neuronal cell death after transient forebrain ischemia in Mongorian gerbil. Furthremore, in the rat middle cerebral artery occlusion model, CNN reduced the infarction area. Our novel chemical compound of CNN can be used as neuroprotective medication even after ischemic disease onset.

Academic Significance and Societal Importance of the Research Achievements

脳血管の閉塞/狭窄による脳虚血状態は神経細胞障害/神経細胞死をもたらす。今まではこの脳梗塞の障害が始まった後には止めることができる有効な薬剤が存在しなかった。我々は今回の研究で新しくL-カルノシンノネナール(CNN)を合成した。このCNNは実際の脳梗塞の治療において脳梗塞の障害が始まった後に投与しても細胞障害の進行に中心的な役割をしている分子4-HNEをを抑制することができる。このことは脳梗塞が発症してもその後の投与で神経細胞障害を予防でき後遺症を極力軽くすることができると考えられる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (13 results)

All 2021 2020 2019

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (4 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] A novel step‐down infusion method of barbiturate therapy: Its safety and effectiveness for intracranial pressure control2021

    • Author(s)
      Yamakawa Yukako、Morioka Motohiro、Negoto Tetsuya、Orito Kimihiko、Yoshitomi Munetake、Nakamura Yukihiko、Takeshige Nobuyuki、Yamamoto Masafumi、Takeuchi Yasuharu、Oda Kazutaka、Jono Hirofumi、Saito Hideyuki
    • Journal Title

      Pharmacology Research & Perspectives

      Volume: 9 Issue: 2

    • DOI

      10.1002/prp2.719

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of the ghrelin/growth hormone secretagogue receptor axis and its functional role in promoting tumor growth in primary central nervous system lymphomas2020

    • Author(s)
      Muta Hiroko、Sugita Yasuo、Furuta Takuya、Shiimura Yuki、Ohshima Koichi、Nakashima Kazutaka、Sato Kensaku、Morioka Motohiro、Abe Hideyuki、Nozawa Takanori、Fujii Yukihiko、Kakita Akiyoshi
    • Journal Title

      Neuropathology

      Volume: - Issue: 3 Pages: 232-239

    • DOI

      10.1111/neup.12634

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] E8002 Inhibits Peripheral Nerve Adhesion by Enhancing Fibrinolysis of l-Ascorbic Acid in a Rat Sciatic Nerve Model2020

    • Author(s)
      Kikuchi Kiyoshi、Setoyama Kentaro、Takada Seiya、Otsuka Shotaro、Nakanishi Kazuki、Norimatsu Kosuke、Tani Akira、Sakakima Harutoshi、Kawahara Ko-ichi、Hosokawa Kazuya、Kiyama Ryoji、Sumizono Megumi、Tancharoen Salunya、Maruyama Ikuro、Hattori Gohsuke、Morioka Motohiro、Tanaka Eiichiro、Uchikado Hisaaki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 11 Pages: 3972-3972

    • DOI

      10.3390/ijms21113972

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of growth hormone biosynthesis by Cdk5 regulatory subunit associated protein 1-like 1 (CDKAL1) in pituitary adenomas2019

    • Author(s)
      Takesue Y, Wei F-Y, Tomizawa K, Morioka M et al.,
    • Journal Title

      Endocrine Journal

      Volume: 66 Issue: 9 Pages: 807-816

    • DOI

      10.1507/endocrj.EJ18-0536

    • NAID

      130007719407

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of GLUT1 in pseudopalisaded and perivascular tumor cells is an independent prognostic factor for patients with glioblastomas2019

    • Author(s)
      Komaki S, Sugita Y, Furuta T, Morioka M et al.,
    • Journal Title

      Journal of Neuropathology and Experimental Neurology

      Volume: 78 Issue: 5 Pages: 389-397

    • DOI

      10.1093/jnen/nly124

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Malignant progression of an extraventricular neurocytoma arising from2019

    • Author(s)
      Sugita Y, Furuta T, Komaki S, Ohshima K, Sakata K, Morioka M
    • Journal Title

      Neuropathology

      Volume: 39 Issue: 2 Pages: 120-126

    • DOI

      10.1111/neup.12533

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Leptomeningeal carcinomatosis following neoplastic cerebral aneurysm rupture: a case report.2019

    • Author(s)
      Koga M, Aoki T, Negoto T, Makizono T, Sugi K, Fujimori K, Kajiwara S, Komaki S, Yoshitomi M, Sugita Y, Morioka M.
    • Journal Title

      World Neurosurg.

      Volume: pii: S1878-8750(19)30469-3. Pages: 0469-3

    • DOI

      10.1016/j.wneu.2019.02.058

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Leakage sign for acute subdural hematoma in clinical treatment.2019

    • Author(s)
      Yamamoto M, Orito K, Nakamura Y, Takeshige N, Yoshitomi M, Takeuchi Y, Uzu H, Takasu O, Abe T, Tanoue S, Uchiyama Y, Morioka M.
    • Journal Title

      Acta Neurochir (Wien).

      Volume: 161(2) Issue: 2 Pages: 233-238

    • DOI

      10.1007/s00701-018-3755-x

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuroprotective effects of a novel carnosine-hydrazide derivative on hippocampal CA1 damage after transient cerebral ischemia.2019

    • Author(s)
      Noguchi K, Ali TFS, Miyoshi J, Orito K, Negoto T, Biswas T, Taira N, Koga R, Okamoto Y, Fujita M, Otsuka M, Morioka M.
    • Journal Title

      Eur J Med Chem.

      Volume: 163 Pages: 207-214

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 脳出血治療に新たな光を求めて2020

    • Author(s)
      森岡基浩、折戸公彦、竹内靖治
    • Organizer
      第45回日本脳卒中学会総会・第49回日本脳卒中の外科学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Factors correlation with CBF, CVR change after revascularization surgery for patients with moyamoya disease2019

    • Author(s)
      Kawano T, Mukasa A, Morioka M
    • Organizer
      5th European Stroke Organisation Conference  2019.5.22-24(Milan)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Neuroprotective effects of a novel carnosine-hydrazide derivative on hippocampal CA1 damage after transient cerebral ischemia.2019

    • Author(s)
      Morioka M, Noguchi K, Orito K, Fujita M, Ali T, Ohtsuka M
    • Organizer
      BRAIN & BRAIN PET 2019 2019.7.4-7(Yokohama)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Leakage sign for intracerebral hemorrhage in relation to the site of hemorrhage2019

    • Author(s)
      Orito K, Yoshitomi M, Yamamoto M, Takeuchi Y, Hirohata M, Morioka M
    • Organizer
      BRAIN & BRAIN PET 2019 2019.7.4-7(Yokohama)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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