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New approach to investigate the mechanisms of Ischemic neuronal death and development for the establishment of new way of brain resuscutator

Research Project

Project/Area Number 14571467
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

UCHINO Hiroyuki  Tokyo Medical University, Medicine, Assistant Professor, 医学部, 講師 (60266476)

Co-Investigator(Kenkyū-buntansha) SHIBASAKI Futoshi  Tokyo Metropolitan Institute of Medical Science, Department of Molecular Physiology, Director, 東京都臨床医学総合研究所, 研究員
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsCalcineurin / Cyclophillin D / CsA / CsJ / NCX / MPT / Brain ischemia / DNA chip / Knock out mouse / 脳虚血 / 神経細胞死 / Cyclophilin D / Calcineurin / MPT / CSJ / Ca2+ exchanger / 脳保護
Research Abstract

Brain ischemia leads to severe damage in the form of delayed neuronal cell death. We have been investigated the mechanisms of delayed neuronal cell death in terms of the mechanisms of immunosuppressant, such a cyclosporin A(CsA) and FK506. From our results, Calcineurin and immunophilin signal transduction casca* play an important roles for neuroprotection, Especially, mitochondrial isomerase cyclophillinD paly a pivotal role to regulate the MPT(Mitochondrial Permeability Transition)pore formation, one of the prolylcis/trans isomerase family members.
We also need further analysis to explore more mechanisms.
These results shed light on the clinical application and development of new drugs for the treatment of ischemic damage in the brain as well as in the heart and liver.

Report

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

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Shibasaki F, Hallin U, Uchino H.: "Calcineurin as a multifunctional regulator"J Biochem(Tokyo). 131(1). 1-15 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Uchino H et al.: "Differential neuroprotection by cyclosporin A and FK506 following ischemia corresponds with differing abilities to inhibit calsineurin and the mitochondrial permeability transition"Neurobiol Dis. 10(3). 219-233 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Siesjo BK, Uchino H, Shibasaki F: "Post treatment in transient global and focal ischemia : new pharmacological avenues."Pharmacology of Cerebral Ischemia. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Uchino, N.Ishii, E.Shibasaki: "Calcineurin and cyclophilin D are differential targets of neuroprotection by Immunosuppressant CsA and FK506 in Ischemic brain damage."Acta Neurochir Supl. 86. 105-111 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 内野 博之, 芝崎 太, Bo.k.Siesj, 一色 淳: "虚血性神経細胞死とカルシニューリン/イムノフィリン系の役割と新規脳蘇生法確立への応用"蘇生. 21. 1-8 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 内野 博之, 芝崎 太, 石井 脩夫: "脳を守るストラテジー1「虚血性神経細胞死の分子機序と薬物療法による脳保護の可能性」"Life support and Anesthesia. 11(1). 1-18 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Keep, H.Uchino, E.Elmer: "Immunosuppressants as neuroprotective agents. Imunosppressant Analogs in Neuroprotection."Eds Cesario V.Borlongan Humana Press. 31 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Uchino H, Minamikawa-Tachino R, Kristian T, Perkins G, Narazaki M, Siesjo BK, Shibasaki F.: "Differential neuroprotection by cyclosporin A and FK506 following ischemia corresponds with differing abilities to inhibit calcineurin and the mitochondrial permeability transition."Neurobiol Dis. 10(3). 219-233 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shibasaki F, Hallin U, Uchino H.: "Calcineurin as a multifunctional regulator."J Biochem (Tokyo). 131(1). 1-15 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Siesjo BK, Uchino H, Shibasaki F: "Post treatment in transient global and focal ischemia : new pharmacological avenues."Pharmacology of Cerebral Ischemia. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Uchino, BK Siesjo, F.Shibasaki: "Calcineurin and immunophilin are pivotal target for delayed neuronal cell death on the forebrain ischemia in the rat."Acta Neurochirurgica Supplement Springer Verlag Wien New York. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Keep, H.Uchino, E.Elmer.: "Immunosuppressants as neuroprotective agents. Imunosppressant Analogs in Neuroprotection."Eds Cesario V.Borlongan Humana Press. 3-32 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] "Calcineurin and cyclophilin D are differential targets of neuroprotection by Immunosuppressant CsA and FK506 in Ischemic brain damage."Acta Neurochir Supl. 105-113 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Uchino, N.Ishii, F.Shibasaki: "Calcineurin and Cyclophilin D are differential targets of neuroprotection by Immunosuppressant CsA and FK506 in ischemic brain damage"Acta Neurochir Supl. 86. 105-113 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 内野 博之, 芝崎 太, 石井 脩夫: "脳を守るストラテジー「虚血性神経細胞死の分子機序と薬物療法による脳保護の可能性」"Life support and Anesthesia. 11(1). 1-18 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 内野 博之, 芝崎 太, 石井 脩夫: "虚血性神経細胞死におけるカルシニューリンの役割"臨床検査. 47. 681-689 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 池田 幸穂, 鬼塚 俊郎, 内野 博之: "急性重症脳障害に対する軽度低体温療法の臨床"Life support and Anesthesia. 11(2). 118-124 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shibasaki F, Ulrika Hallin, Hiroyuki Uchino: "Calcineurin as a multifunctional regulator"J. Biochem. 131. 1-15 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 内野博之, 芝崎 太, Bo.K.Siesjo, 一色 淳: "虚血性神経細胞死とカルシニューリン/イムノフィリン系の役割と新規脳蘇生法確立への応用"蘇生. 21. 1-8 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Uchino H et al.: "Differential Neuroprotection by Cyclosporin A and FK506 following ischemia corresponds with differing abilities to inhibit calcineurin and mitochondrial permeability transition"Neurobiol. Dis. 10. 219-233 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 内野博之, 芝崎太, 石井脩夫: "虚血性神経細胞死のメカニズムと脳保護"Lisa. 9. 330-350 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 内野博之, 芝崎太, 石井脩夫: "薬理学的アプローチによる脳保護と21世紀における脳蘇生の展望"Lisa. 9. 352-362 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hiroyuki Uchino et al.: "Pivotal role for Neuroprotection by differential immunosuppressants following rat global ischemia corresponds with differing abilities toinhibit calcineurin and the mitochondrial permeability transition"7th Brain Edema proceeding. (in press).

    • Related Report
      2002 Annual Research Report

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

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