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The mechanisms of ischemic neuronal death and its treatment.

Research Project

Project/Area Number 05305006
Research Category

Grant-in-Aid for Co-operative Research (A)

Allocation TypeSingle-year Grants
Research Field 広領域
Research InstitutionEhime University School of Medicine

Principal Investigator

KATAOKA Kiyoshi  Ehime University School of Medicine, Department of Physiology, Professor, 医学部, 教授 (20025589)

Co-Investigator(Kenkyū-buntansha) YONEDA Yukio  Setsunan University, Department of Pharmacology, Associate Professor, 薬学部, 助教授 (50094454)
FUJISHIMA Masatoshi  Kyusyu University School of Medicine, Department of Internal Medicine, Professor, 医学部, 教授 (80038760)
HAYAKAWA Toru  Osaka University School of Medicine, Department of Neurosurgery, Professor, 医学部, 教授 (20135700)
TAMURA Akira  Teikyo University School of Medicine, Department of Neurosurgery, Professor, 医学部, 教授 (80111532)
KIRINO Takaaki  Tokyo University School of Medicine, Department of Neurosurgery, Professor, 医学部, 教授 (90126045)
岡田 安弘  神戸大学, 医学部, 教授 (40073069)
桐野 高明  東京大学, 医学部, 教授 (10161605)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1995: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1994: ¥3,000,000 (Direct Cost: ¥3,000,000)
KeywordsIschemic neuronal death / Excitotoxicity / Remote effects / Resistance to ischemia / Mild hypothermia / Glial cells / Red cell deformability / Transcription factor / 脳虚血 / グルタミン酸受容体 / FK506 / プログラム死 / スライス培養 / 加齢 / AP-1 / 虚血ストレス / クルシウム / ユビキチン / 海馬スライス / 虚血性ニューロン死 / グルタミン酸放出 / カルシウム / 低脳温 / 蛋白質代謝 / 遠隔領域障害
Research Abstract

Following the early process in ischemic neurons, a glutamate surge and a subsequent calcium mobilization, proceed further complicated intracellular cascade reactions, being tangled with environmental changes including glial responses, which eventually lead to irreversible neuronal damage. The present project intended to posturate these patho-physiological entity on different aspects and by different methods. Examples of means to protect ischmic neurons against damage were also demonstrated.
As experimental models, primary culture systems of cells and also of slices were newly developed along with forebrain or regional ischemic models (Hayakawa and others). As the very early phase of ischemia, glutamate release and calcium mobilization, and suppressive effects of mild hypothermia thereto were demonstrated (Kataoka and others). Mechanisms of intracellular calcium dischage were studied by newly synthesized inositol polyphosphoric acids ; and dantrolene derivatives were studied on their neu … More roprotective activities (Ozaki and others). As the cascade reactions, an ischemia-induced enhancement of the binding activity of a transcription factor, AP1, was posturated with a speculation of its relation to neuronal survival (Yoneda and others). Dysfunction of protein metabolism and special synthetic response to ischemia were studid by the use of heat shock protein or ubiquitin (Kirino and others). Apoptotic mechanisms were proposed to be involved in ischemic damage through the studies of related genes and analysis of phospholipids (Tamura and others). Specific resistance to ischemia and the importance of glucose were demonstrated in neurons of new born animals (Okada and others). On the other hand, regional cerebral blood flow were found lowered in neurons of aged animals along with elevated stress responses (Fujishima and others). A device for analysis of red cell deformability was newly developed and an enhancement of the deformability was shown in red cells from spontaneously hypertensive rats (Uyesaka and others). Less

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [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(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kanemitsu H.,et al.: "Key of induced tolerance to ischaemia in gerbil hippocampal CA1 is no 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
      1995 Final Research Report Summary
  • [Publications] Mitani A.,et al.: "Origin of Ischemia-induced glutamate efflux in the CA1 field of the gerbil hippocampus : An in vivo brain microdialysis study." J.Neurochem.63. 2152-2164 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tsuji K.,et al.: "Rapid decrease in ATP content without recovery phase during glutamate-induced cell death in cultured spinal neurons." Brain Res.662. 289-292 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Okada M., et al.: "Long term spatial cognitive impairment following middle cerebral artery occlusion in rats." J.Gereb.Blood Flow Metab.15. 505-512 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nabetani,M.,et al.: "Neural activity and the levels of high energy phosphates during deprivation of oxygen and/or glucose in hippocampal slices of immature and adult rats." Int.J.Devl.Neuroscince. 13. 3-12 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 桐野高明: "脳と発達" 診断と治療社, (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 中村洋一: "神経精神薬理" 星和書店, (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 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
      1995 Final Research Report Summary
  • [Publications] Kanemitsu H., et al.: "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
      1995 Final Research Report Summary
  • [Publications] Mitani A., et al.: "Origin of Ischeima-induced glutamate efflux in the CA1 field of the gerbil hippocampus : An in vivo brain microdialysis study." J.Neurochem.63. 2152-2164 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tsuji K., et al.: "Rapid decrease in ATP content without recovery phase during glutamate-induced cell death in cultured spinal neurons." Brain Res.662. 289-292 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Okada M., et al.: "Long-term spatial cognitive impairment following middle cerebral artery occlusion in rats." J.Cereb.Blood Flow Metab. 15. 505-512 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nabetani, M., et al.: "Neural activity and the levels of high energy phosphates during deprivation of oxygen and/or glucose in hippocampal slices of immature and adult rats." Int.J.Devl.Neuroscience. 13. 3-12 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Nabetani,et al: "Neural activity and the levels of high energy phosphates during deprivation of oxygen and/or glucose in hippocampal slices." Int.J.Devl.Neuroscience. 13. 3-12 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] M.Okada,et al: "Long-term spatial cognitive impairment following middle cerebral artery occl usi on in rats." J.Cereb.Blood Flow Metab.15. 505-512 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T.Ide,et al: "An immunosuppressant,FK506,protects hippocampal neurons from forebrain ischemia in the Mongolian gerbil." Neurosci.Lett.(in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] H.Ooboshi,et al: "Ischemia-induced release of amino acids in the hippocampus of aged hypertensive rats." J.Cereb.Blood Flow Metab.15. 227-234 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] A.Mitani,et al: "In vitro Ischemia-induced intracellular Ca^<2+> elevation in cerebellar slices." Acta Neuropathol.89. 2-7 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T.Ogata,et al: "A possible mechanism for the hypoxia-hypoglycemia induced release of excitatory amino acids from cultured hippocampal slice" Neurochem.Res.20. 737-743 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 桐野 高明: "脳と発達" 診断と治療社, 130-135 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 久保田 勝: "BRAIN and NERVE" 医学書院, 756-761 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] A.Mitani,et al.: "Changes in intracellular Ca2+ and energy levels during in vitro ischemia in the gerbil hippocampal slice." J.Neurochem.62. 626-634 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Kanemitsu,et al.: "Key of induced tolerance to ischaemia in gerbil hippocampal CA1 is not at transcriptional level of hsp70 gene." Neurol Res.16. 209-212 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Sakaguchi,et al.: "Expression of basic fibroblast growth factor receptor messenger RNA in the periinfarcted brain tissue." Restorotive Neurology and Neuroscience. 7. 29-36 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Yao,et al.: "Cerebral blood flow and ischemia-induced neurotransmitter release in the striatum of aged spontaneously hypertensive rats." Stroke. 24. 577-580 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Ogita,et al.: "Selective potentiation of DNA binding activities of both activator protein 1 and cyclic AMP response element binding protein." J.Neurochem.63. 525-534 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Nakamura,et al.: "Rheologic and pathophysiologic significance of red cell passage through parrow pores." Blood Cells. 20. 151-165 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kataoka K,et al.: "Binding of〔^3H〕MK-801,NMDA-displaceable〔^3H〕glutamate,〔^3H〕glycine,〔^3H〕spermidine,〔^3H〕kainate and〔^3H〕AMPA to regionally discrete brain membranes." Neurochem.Int.22. 37-43 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mitani A,et al.: "Origin of intracellular Ca^<2+> elevation induced by in vitro ischemia-like condition in hippocampal slices." Brain Res.601. 103-110 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nakamura Y,et al.: "Glial plasmalemmal vesicles:A subcellular fraction from rat hippocampal homogenate distinct from synaptosomes." Glia. 9. 48-56 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Zhang L,et al.: "Dantrolene protects against ischemic,delayed neuronal death in gerbil brain." Neurosci.Lett.158. 105-108 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ogata T,et al.: "Steroid hormones protect spinal cord neurons from glutamate toxicity." Neuroscience. 55. 445-449 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mitani A,et al.: "Changes in intracellular Ca^<2+> and energy levels during in vitro vitro ischemia in the gerbil hippocampal slice." J.Neurochem.(in press). (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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