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Mechanism of Neuronal Cell Death following Cerebral Ischemia

Research Project

Project/Area Number 05404049
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Cerebral neurosurgery
Research InstitutionUniversity of Tokyo

Principal Investigator

KIRINO Takaaki  University of Tokyo, Facultiy of Medicine, Department of Nerosurgery, Professor, 医学部(病), 教授 (90126045)

Co-Investigator(Kenkyū-buntansha) MORIKAWA Eiharu  University of Tokyo, Faculty of Medicine, Department of Nerosurgery, Assistant, 医学部(病), 助手 (90251256)
MORIMOTO Tadashi  University of Tokyo, Faculty of Medicine, Department of Nerosurgery, Assistant, 医学部(病), 助手 (20230154)
SASAKI Tomio  University of Tokyo, Faculty of Medicine, Department of Nerosurgery, Associate P, 医学部(病), 助教授 (10134561)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥34,300,000 (Direct Cost: ¥34,300,000)
Fiscal Year 1994: ¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 1993: ¥22,500,000 (Direct Cost: ¥22,500,000)
KeywordsCerebral ischemia / Cell daeth / Hippocampus / Mongolian gerbil / Stress protein / Protein synthesis / Ubiquitin / Synapse / 免疫染色 / cerebral ischemia / neuronal death / stress response / protein synthesis / excitotoxin / presynaptic terminal / ubiqutin
Research Abstract

Neurons in the hippocampal CA1 sector die following brief period of ischemia. The neuronal injury here is almost purely postsynaptic. The long term change in remaining presynaptic terminals was studied by fine structural morphometry. The terminals were chronically maintained for longer than 3 months and gradually decreased in number. The CA1 region fell in atrophy in accordance with disappearance of residual presynaptic terminals. Brief ischemia, which in itself is not lethal to hippocampal neurons, confer tolerance to further ischemia even if the ischemic insult is lethal to neurons in intact condition. In neurons which have acquired ischemic tolerance, a stress protein, hsp70, is strongly expressed. We studied the change in protein synthesis in tolerance-induced neurons by autoradiography. Following ischemia, protein synthesis is severely inhibited in Ca1 and never recovers. On the other hand, in tolerance-induced animals, the recovery of protein synthesis was rapid even if ischemia was of lethal level. The change in mRNA for hsp70 was studied by in situ hybridization method. The message was always expressed in CA1 neurons even if the neurons were going to die. Following tolerance induction, mRNA expression was followed by intense expression of hsp70 protein. Another stress-inducible protein, ubiquitin, was known to disappear in CA1 neurons following ischemia. However, this was not the case when we used another type of anti-ubiquitin antibody which recognize mainly conjugated form of ubiquitin. Immunoblot and immunoprecipitation study revealed that uniqutin does not decrease in total amount but free form of ubiquitin is depleted from the CA1 neurons following ischemia. The role of the disappearance of free ubiquitin in ischemic neuronal death is still unknown.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Ishiguro H: "Expression of the large myelin-associated glycoprotein isoform in rat oligodendrocytes around cerebral infarcts" Mol Chem Neuropathol. 20. 173-179 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 桐野高明: "Presynaptic terminals in hippocampal gliosis following transcient ischemia in the Mongolian gerbil" Prog Brain Res. 96. 261-270 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nakagomi T: "Early recovery of protein synthesis following ischemia in hippocampal neurons with induced torerance in the gerbil" Acta Neuropathol(Berl). 86. 10-15 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kanemitsu H: "Key of induced torerance to ischemia in gerbil hippocampal CA1 is not at transcriptional level of hsp70 gene In situ hybridization of hsp70 mRNA" Neurol Res. 16. 209-212 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 桐野高明: "脳のエネルギー代謝障害と神経細胞死" 神経精神薬理. 15. 35-44 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 桐野高明: "遅発性神経細胞死の臨床的意義" 日本内科学会雑誌. 83. 828-833 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ishiguro H,Inuzuka T,Fujita N,Sato S,Nakano R,Tamura A,Kirino T,Miyatake T: "Expression of the large myelin-associated glycoprotein isoform in rat oligodendrocytes around cerebral infarcts." Mol Chem Neuropathol. 20. 173-179 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kirino T: "Presynaptic terminals in hippocampal gliosis following transient ischemia in the Mongolian gerbil." Prog Brain Res. 96. 261-270 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nakagomi T,Kirino T,Kanemitsu H,Tsujita Y,Tamura A: "Early recovery of protein synthesis following ischemia in hippocampal neurons with induced tolerance in the gerbil." Acta Neuropathol (Berl). 86. 10-5 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kanemitsu H,Kirino T,Nakagomi T,Tsujita Y,Iwamoto T,Tomich JM,Tamura A: "Key of induced tolerance to ischaemia in gerbil hippocampal CA1 is not at transcriptional level of hsp70 gene : In situ hybridization of hsp70 mRNA." Neurol Res. 16. 209-212 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kirino T: "Brain energy metabolism and neuronal cell death" Seishinshinkeiyakuri. 15. 35-44 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kirino T: "Clinical significance of delayd neuronal death" Nihonnaikagakkaizasshi. 83. 828-833 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kanemitsu H: "Key of induced tolerance to ischemia in gerbil hippocampal CAl is not at transcriptional level of hsp70 gene" In situ hybridization of hsp70. 16. 209-212 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 桐野 高明: "脳虚血とグルタミン酸レセプター -虚血性神経細胞死のグルタミン酸・カルシウム仮説-" Dementia. 7. 161-171 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 桐野 高明: "海馬と遅発性神経細胞死" Clinical Neuroscience. 12. 61-65 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 桐野 高明: "脳のエネルギー代謝障害と神経細胞死" 神経精神薬理. 15. 35-44 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 桐野 高明: "遅発性神経細胞死の臨床的意義" 日本内科学会雑誌. 83. 828-833 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 桐野 高明: "脳虚血と神経細胞死" 脳と発達. 26. 130-135 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 桐野 高明: "赤池 紀扶,小暮 久也編「脳機能の解明-分子から病態まで」" 創風社, (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 森川 栄治: "虚血性神経細胞治療の試み-Annual Revieu神経" 中外医学社, (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kirino T: "Presynaptic terminals in hippocampal gliosis following transient ischemia in the Mongolian gerbil." Prog Brain Res. 96. 261-270 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nakagomi T: "Early recovery of protein synthesis following ischemia in hippocampal neurons with induced tolerance in the gerbil." Acta Neuropathol(Berl). 86. 10-15 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 桐野 高明: "脳のエネルギー代謝障害と神経細胞死" 神経精神薬理. 15. 35-44 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 中込 忠好: "遅発性神経細胞壊死Delayed neuronal death" Current Therapy. 11. 141-144 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 桐野 高明: "遅発性神経細胞死" 総合臨床. 42. 3342-3326 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 桐野 高明: "脳虚血とグルタミン酸レセプター-虚血性神経細胞死のグルタミン酸・カルシウム仮説-" Dementia. 7. 161-171 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 桐野 高明: "神経科学レビュー7(分担) (PP83-104)" 医学書院, 139 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 桐野 高明: "Annual Review神経(分担) (PP119-131)" 中外医学社, 414 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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