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Protective effects of moderate hypothermia onneuronal death.

Research Project

Project/Area Number 03557007
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Neurophysiology and muscle physiology
Research InstitutionEhime University

Principal Investigator

KATAOKA Kiyoshi  Ehime Univ. Dept. Physiol. Pro. Sch. of Med., 医学部, 教授 (20025589)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Yoichi  Ehime Univ. Dept. Physiol. Pro. Sch. of Med.Instructor, 医学部, 助手 (90180413)
MITANI Akira  Ehime Univ. Dept. Physiol. Pro. Sch. of Med.Associate Pro., 医学部, 助教授 (50200043)
Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsischemic neuronal death / moderate hypothermia / culture / glutamate / calcium / MK-801 / blood-viscosity / neuronal protection / スナネズミ / 海馬 / 脳温 / マイクロダイアリシス / 遅発性ニュ-ロン死 / ニュ-ロン保護作用
Research Abstract

In the first report of the present research project, we described that a slight lowering of the cerebral temperature caused a striking neuroprotection against ischemic damage. Since materials employed are of in vivo system or in vitro slices, rather functionally integrated ones, we attempted in this fiscal year (1) to use more simplified system, primary culture. Then we analyzed (2) the mode of action of MK-801, a chemical which has a nature to lower cerebral temperature and examined (3) the effect of the slight temperature lowering on blood viscosity, a problem which may be raised in clinical application of this procedure. Results obtained are as follow.
(1)The primary culture experiments. When rat spinal neurons in culture were exposed to 200muM glutamate for 15min, and activity of liberated lactic dehydrogenase was analyzed to measure neuronal damage, there was practically no difference, between at 33゚C and 37゚C, in the extent of the death. It is deducible that effect of the lowering … More temperature can be observed in more integrated system in the term of their functions.
(2)Mode of action of MK-801. MK-801, a non-selective antagonist of NMDA-type glutamate receptor subtype, apparently shows a marked neuroprotection by its temperature lowering action. In order to clarify this process, we attempted to follow cerebral temperature using a remote monitoring system that we developed newly. We found from these experiments that MK-801 does lose the set point of the cerebral temperature to allow the experimental animal to follow room temperature, a condition very mimic to poikilothermia.
(3)Effect of temperature on blood viscosity of the dog. Under deep anesthesia and with a carotid-bypass, hypothermic dog was prepared. Blood samples from jugular vein were subjected to viscosity measurement using a cone-plate viscosimeter. At 21 sec shear rate, blood with Hematocrit 40 showed several % increase in the CP value (viscosity) by lowering blood temperature by 4゚C, a finding which is very akin to human blood. Less

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] K.KATAOKA: "Binding of [^3H]MK-801,NMDA-displaceable[^3H]glutamate,[^3H]glycine,[^3H]spermidine,[^3H]kainate and [^3H]AMPA to regionally discrete brain membranes of the gerbil." Neurochem.Internat.22. 37-43 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] A.MITANI: "Origin of intracellular Ca^<2+> elevation induced by in vitro ischemia-like condition in hippocampal slices." Brain Res.601. 103-110 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] A.MITANI: "Selective vulnerability of hippocampal CAl neurons cannot be explained in terms of an increase in glutamate concentration during ischemia in the gerbil." Neuroscience. 48. 307-313 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y.ANDOU: "Re-evaluation of ischemia-induced neuronal damage in hippocampal regions in the normothermic gerbil." Acta Neuropathol.85. 10-14 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] A.MITANI: "Acidic fibroblast growth factor delays in vitro ischemia-induced intracellular calcium elevation in gerbil hippocampal slices." Neurochem.Internat.21. 337-341 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.OGATA: "Release of excitatory amino acids from cultured hippocampal astrocytes induced by a hypoxic-hypoglycemic stimulation." J.Neurochem.58. 1957-1959 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.KATAOKA: "New Horizons in Aging and Science." University of Tokyo Press, 510 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.KATAOKA: "The Role of Neurotransmitters in Brain Injury." Plenum Press, 378 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.Kataoka: "Binding of [^3H]MK-801, NMDA-displaceable [^3H]glutamate, [^3H]glycine, [^3H]spermidine, [^3H]kainate, and [^3H]AMPA to regionally discrete brain membranes of the gerbil." Neurochem. Internat.22. 37-43 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] A.Mitani: "Origin of intracellular Ca^<2+ elevation> induced by in vitro ischemia-like condition in hippocampal slices." Brain Res.601. 103-110 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] A.Mitani: "Selective vulnerability of hippocampal GAl neurons cannot be explained in terms of an increase in glutamate concentration during ischemia in the gerbil." Neuroscience. 48. 307-313 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y.Andou: "Re-evaluation of ischemia-induced neuronal damage in hippocampal regions in the normothermic gerbil." Acta Neuropathol.85. 10-14 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Ogata: "Release of excitatory amino acids from cultured hippocampal astrocytes induced by a hypoxic-hypoglycemic stimulation." J.Neurochem.58. 1957-1959 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] A.Mitani: "Acidic fibroblast growth factor delays in vitro ischemia-induced intracellular calcium elevation in gerbil hippocampal slices." Neurochem.Internat.21. 337-341 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.Kataoka: "Role of glutamate and calcium in early stage of ischemic delayed neuronal damage." New Horizons in Aging and Science.University of Tokyo Press (510). 439-440 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.Kataoka: "Topographical dissociation of calcium accumulation following hypoxic-hypoglycemic glutamate release." The Role of Neurotransmitters in Brain Injury.Plenum Press (378). 57-61 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.Kataoka: "Binding of 〔^3H〕MK-801,NMDA-displaceable 〔^3H〕glutamate,〔^3H〕glycine,〔^3H〕spermidine,〔^3H〕kainate and 〔^3H〕AMPA to regionally discrete brain membranes of the gerbil." Neurochem.Internat.22. 37-43 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] A.Mitani: "Origin of intracellular Ca^<2+> elevation induced by in vitro ischemia-like condition in hippocampal slices." Brain Res.601. 103-110 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] A.Mitani: "Selective vulnerability of hippocampal CA1 neurons cannot be explained in terms of an increase in glutamate concentration during ischemia in the gerbil." Neuroscience. 48. 307-313 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.Andou: "Re-evaluation of ischemia-induced neuronal damage in hippocampal regions in the normothermic gerbil." Acta Neuropathol.85. 10-14 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] A.Mitani: "Acidic fibroblast growth factor delays in vitro ischemia-induced intracellular calcium elevation in gerbil hippocampal slices." Neurochem.Internat.21. 337-341 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Ogata: "Release of excitatory amino acids from cultured hippocampal astrocytes induced by a hypoxic-hypoglycemic stimulation." J.Neurochem.58. 1957-1959 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Kataoka: "New Horizons in Aging and Science." University of Tokyo Press., 510 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Kataoka: "The Role of Neurotransmitters in Brain Injury." Plenum Press, 378 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Akira Mitani: "Temperature dependence of hypoxia-induced calcium accumulation in gerbil hippocampal slices." Brain Res.562. 159-163 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Akira Mitani: "Visualization of hypoxia-induced glutamate release in gerbil hippocampal slice." Neurosci.Lett.122. 167-170 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Akira Mitani: "Transient forebrain ischemia of three-mi nute duration consistenly induces severe neuronal damage in field CA1 of the hippocampus in the normothermic gerbil." Neurosci.Lett.131. 171-174 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hitoshi Imon: "Delayed neuronal death is induced without postischemic hyperexcitability:continuous multiple-unit recording from ischemic CA1 neurons." J.Cereb.Blood Flow Metab.11. 819-823 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Akira Mitani: "Selective vulnerability of hippocampal CA1 neurons cannot be explained in terms of an increase in glutamate concentration during ischemia in the gerbil:brain microdialysis study." Neuroscience. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tadanori Ogata: "Release of excitatory amino acids from cultured hippocampal astrocytes induced by a hypoxia-hypoglycemic stimulation." J.Neurochem.in press. (1992)

    • Related Report
      1991 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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