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The role of arachidonic acid cascade in the development of delayed neuronal death

Research Project

Project/Area Number 01570802
Research Category

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

Allocation TypeSingle-year Grants
Research Field Cerebral neurosurgery
Research InstitutionTeikyo University School of Medicine (1991)
The University of Tokyo (1989-1990)

Principal Investigator

NAKAGOMI Tadayoshi  Teikyo Univ., Neurosurgery, Assistant Prof., 医学部, 講師 (90198052)

Co-Investigator(Kenkyū-buntansha) SASAKI Tomio  Tokyo Univ., Neurosurgery, Assis. Prof., 医学部, 講師 (10134561)
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1991: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1990: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1989: ¥800,000 (Direct Cost: ¥800,000)
Keywordscyclooxygenase / lipoxygenase / indomethacin / delayed neronal death / hippocampus / gerbil / immunohistochemistry / prostaglandin / 脳虚血
Research Abstract

The role of arachdonic acid cascade in the develppent of delayed neuronal death following forebrain ischemia was investigated in the gerbils. First, immunohistochemical localization of prostaglandin(PG)F_<2alpha> synthesized during the recirculation phase following ischemia was studied. Frozen sebtions containing hippocampi were incubated with rabbit anti-PGF_<2alpha> serum and stained by the avidin-biotin-peroxidase complex method. In the control animals having sham operation, blood vessels were faintly stained with anti-PGF_<2alpha> serum. Less or no stain was found in neurons and glial cells. After recirculation, the experimental animals demonstrated marked positive staining for PGF_<2alpha> in blood vessels, neurons, especially hippocampal pyramidal neurons, and glial cells. Next, we examined the possibility that indomethain, a cyclooxygenase inhibiro, prevents ischemic delayed neuronal death in the gerbil hippocampus. Forebrain ischemia for 5 min was prduced by bilateral carotid occlusion. Animals received intraperitoneal injection of indomethacin(1, 2, 5 and 10mg/kg)30 min before ischemic insult. They were perfusion-fixed 7 days afere ischemic insult, and the neuronal density in the CA_1 sector was counted. Indomethacin at each dose significantly prevented delaye neuronal death in the hippocampal CA_1 sector. Effects of cyclooxygenase inhibior other than indomethacin and lipoxygenase inhibior delayed neuronal death were also examined in the same gerbil model. Piroxycam(10mg/kg)and Flurbiprofen(10mg/kg)ameliorated significantly delayed neuronal death. However, lipoxygenase inhibiotrs, AA801 and BW755C, did not ameliorated delayed neuronal death. Above results strongly suggest that cylooxygenase products may involved in the development of delayed neuronal death following forebrain ischemia in the ferels.

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] 佐々木 富男,中込 忠好,桐野 高明,田村 晃,野口 信,斉藤 勇,高倉 公朋: "インドメタシンによる海馬CA_1遅発性神経壊死の抑制" 医学のあゆみ. 145. 189-190 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 中込 忠好,佐々木 富男,小川 寿幸,野口 信,斉藤 勇,高倉 公朋: "前脳虚血、再開通後に増加するprostaglandin F_2の局在" 医学のあゆみ. 146. 533-534 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 佐々木 富男,小川 寿幸,中込 忠好,Kassell NF,高倉 公朋: "脳虚血とプロスタグランディン産生" 現代医療. 20. 125-130 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sasaki T,Nakagomi T,Kirino T,Tamura A,Noguchi M,Saito I,Takakura K: "Indomethacin ameliorates ischemic neuronal damage in the gerbil hippocampal CA1 sector." Stroke. 19. 1399-1403 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Nakagomi T,Sasaki T,Kirino T,Noguchi M,Saito I,Takakura K: "Effect of cyclooxygenase and lipoxygenase inhibitors on delayed neuronal death in the gerbil hippocampus." Stroke. 20. 925-929 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Nakagomi T,Sasaki T,Ogawa H,Noguchi M,Saito I,Takakura K: "Immunohistochemical localization of prostaglandin F2α in reperfused gerbil brain." Neurol Med Chir. 30. 223-228 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sasaki T, Nakagomi T, Kirino T, Tamura A, Noguchi M, Saito I, Takakura K :"Indomethacin ameliorates ischemic neuronal damage in the gerbil hippocampal CA_1 sector." Stroke. 19. 1399-1403 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Nakagomi T, Sasaki T, Kirino T, Tamura A, Noguchi M, Saito I, Takakura K :"Effect of cyclooxygenase and lipoxygenase inhibitors on delayed neuronal death in the gerbil hippocampus." Storke. 20. 925-929 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ogawa H, Kassell NF, Sasaki T, Nakagomi T, Hongo K, Tsukahara T :"Rapid increase of prostaglandin F_2-alpha inneurons after subarachnoid hemorrhage in rats : an immunohistochemical study." Acta Neuropatho. 178. 621-628 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sasaki T, Nakagomi T, Noguchi M, Saito I, Takakura K, Shimizu T, Sawada M :"Topography of prostaglandin synthesis in ischemic brain. In : Medical Biochemical and Chemical Aspects of Free Radicals." Elsevier Science Publishers. 1081-1087 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Nakagomi T, Sasaki T, Ogawa H, Noguchi M, Saito I, Takakura K :"Immunohistochemical localization of prostaglandin F_2alpha in reperfused gerbil brain." Neurol Med Chir. 30. 223-228 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T.Nakagami et al.: "Effect of cyclooxygenase and lipoxygenase inhibitors on delayed neuronal death in the gerbil hippocampus" stroke. 20. 925-929 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] 佐々木富男,中込忠好,桐野高明,田村晃,野口信,斉藤勇,高倉公明: "インドメタシンによる海馬CA_1遅発性神経壊死の抑止" 医学のあゆみ. 145. 189-190 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] 中込忠好,佐々木富男,小川寿幸,野口信,斉藤勇,高倉公明: "前脳虚血、再開通後に増加するprostaglandin F_2αの局在" 医学のあゆみ. 146. 533-534 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] 佐々木富男,小川寿幸,中込忠好,Kassell NF,高倉公明: "脳虚血とプロスタグランディン産生" 現代医療. 20. 125-130 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] Sasaki T,Nakagomi T,Kirino T,Tamura A,Noguchi M,Saito I,Takakura K: "Indomethacin ameliorates ischemic neuronal damage in the gerbil hippocampal CA,sector" Storoke. 19. 1399-1403 (1988)

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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