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Investigation on therapeutic potentials of inducing ischemic tolerance against ischemic neuronal damage in the spinal cord

Research Project

Project/Area Number 14370490
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionYamaguchi University

Principal Investigator

SAKABE Takefumi  Yamaguchi Univ., School of Medicine, Professor, 医学部, 教授 (40035225)

Co-Investigator(Kenkyū-buntansha) MATSUMOTO Mishiya  Yamaguchi Univ., School of Medicine, Associate Professor, 医学部, 助教授 (60243664)
FUKUDA Shirou  Yamaguchi Univ., Hospital, Research Associate, 医学附属病院, 助手 (70322245)
NAKAI Akira  Yamaguchi Univ., Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (60252516)
MORIMOTO Yasuhiro  Yamaguchi Univ., Hospital, Assistant Professor, 医学附属病院, 講師 (60325230)
中木村 和彦  山口大学, 医学部, 助教授 (50180261)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2004: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2003: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥7,600,000 (Direct Cost: ¥7,600,000)
KeywordsCentral nervous system / Ischemic tolerance / Hyperbaric oxygen / Genomic response / 中枢神絳 / 虚血 / 耐性誘導 / 高圧酸素 / 耐性関連因子
Research Abstract

Paraplegia is a serious complication caused by spinal cord ischemia during thoracoabdominal aneurysm surgery. Preventive and therapeutic measures are not established. Accumulated data show that central nervous system acquires tolerance against ischemic insult when the neuronal tissues are exposed to non-lethal stress before it is subjected to lethal insult. In the present study we examined the effects of hyperbaric oxygen (HBO) on neuronal survival after ischemia and the mechanism for ischemic tolerance.
We used ischemic model in rats and rabbits. Preconditioning with HBO was performed at 2.5〜3.5 ATA (1h/day for 5days). Sequential changes of gene expression and of translated protein were evaluated using DNA microarray, Western blotting, and RT-PCR. In the rabbit that received preconditioning with a short period of ischemia, HSP-70 was detected in the cytoplasm in the motor neurons in the spinal cord. In rats, genes of glutathione peroxidase and hypoxia inducible factor-1 (HIF-1) were detected in the spinal cord. When the animals were subjected to 8-min forebrain ischemia following HBO treatment, neuronal death in the hippocampal CA1 was markedly curtailed, the amelioration being most prominent at 12 hour after HBO. Cluster analysis of the genomic response demonstrated expressions of p75 neurotrophin receptor (p75NTR) and CCAAT-enhancer binding protein δ(C/EBPδ). These changes were confirmed also with RT-PCR and Western blotting.
The results suggest that the signal transduction related to nerve growth factor receptor and inflammatory/immune response is involved in ischemic tolerance in the central nervous system. Modulation of these related genes may provide new therapeutic strategy against ischemic damage in the central nervous system.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (12 results)

All 2004 2002 Other

All Journal Article (10 results) Publications (2 results)

  • [Journal Article] 徹底分析シリーズ 脳を守るスロラテージー1 虚血耐性誘導の脳・脊髄保護法への応用2004

    • Author(s)
      坂部武史 他
    • Journal Title

      LiSA 11(1)

      Pages: 16-20

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 脳におけるPreconditioningと麻酔2004

    • Author(s)
      坂部武史 他
    • Journal Title

      臨床麻酔 28(9)

      Pages: 1471-1480

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 腹部大動脈瘤手術時の脊髄保護2004

    • Author(s)
      松本美志也 他
    • Journal Title

      麻酔 53(10)

      Pages: 1106-1129

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Application of ischemic tolerance-induction to protection of the brain and spinal cord.2004

    • Author(s)
      Takefumi Sakabe, et al.
    • Journal Title

      LiSA 11(1)

      Pages: 16-20

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Preconditioning in central nervous system and anesthesia2004

    • Author(s)
      Takefumi Sakabe, et al.
    • Journal Title

      Rinshomasui 28(9)

      Pages: 1471-1480

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Spinal cord protection during thoracoabdominal aneurysm surgery.2004

    • Author(s)
      Mishiya Matsumoto, et al.
    • Journal Title

      Masui 53(10)

      Pages: 1106-1129

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 脳におけるPreconditioningと麻酔2004

    • Author(s)
      坂部武史 他
    • Journal Title

      臨床麻酔 28・9

      Pages: 1471-1480

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 腹部大動脈瘤手術時の脊髄保護2004

    • Author(s)
      松本美志也 他
    • Journal Title

      麻酔 53・10

      Pages: 1106-1129

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 脳・脊髄の虚血耐性2002

    • Author(s)
      坂部武史 他
    • Journal Title

      ICUとCCU 26(12)

      Pages: 1007-1017

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Ischemic preconditioning in the brain ans spinal cord.2002

    • Author(s)
      Takefumi Sakabe, et al.
    • Journal Title

      ICU & CCU 26(12)

      Pages: 1007-1017

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] 坂部武史 他: "脳・脊髄の虚血耐性"ICUとCCU. 26巻12号. 1007-1017 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 坂部武史 他: "徹底分析シリーズ 脳を守るスロラテージー1 虚血耐性誘導の脳・脊髄保護法への応用"LiSA. 11巻1号. 16-20 (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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