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2001 Fiscal Year Final Research Report Summary

Effect of mild hypothermia and hyperthermia on excitatory amino acid-induced brain damage

Research Project

Project/Area Number 10671305
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionYamaguchi University

Principal Investigator

FUJISAWA Hirosuke  Yamaguchi University, Hospital, Department of Neurosurgery, Lecturer, 医学部・附属病院, 講師 (50238565)

Co-Investigator(Kenkyū-buntansha) MAEKAWA Tsuyoshi  Yamaguchi University, School of Medicine, Department of Critical Care Medicine, Professor, 医学部, 教授 (60034972)
Project Period (FY) 1998 – 2001
Keywordsexcitatory amino acids / glutamate / hypothermia / hyperthermia / microdialysis / histology / nitric oxide / autoradiography
Research Abstract

Excessive glutamate is lethal to neurons, and the concept of glutamate excitotoxicity has become widely accepted. The purpose of this study was to examine the effects of mild hypothermia and hyperthermia on glutamate excitotoxicity. Glutamate-induced cortical lesions were produced in hypothermic (32℃), normothermic (37℃) and hyperthermic (40℃) rats by perfusion of a 0.5 M glutamate solution via a microdialysis probe. 1) The volume of the lesion 7 days after glutamate perfusion was quantified histologically by image analysis of the lesion. The volume of damage was reduced by mild hypothermia and enlarged by mild hyperthermia. 2) Histological changes in normo- and hypothermic animals were studied using monoclonal antibodies against GFAP (for astrocytes) and ED1 (for macrophages) 0, 1, 3 and 5 days after glutamate perfusion. TUNEL staining was used for evaluation of apoptosis. Mild hypothermia delays macrophage proliferation and apoptosis. 3) In order to examine the effects of mild hypothermia on glutamate-induced NO synthesis, the NO end-products which was observed under the normothermic condition. Both of two No synthase inhibitors (L-NAME, 7-NI) also inhibited the glutamate-induced NO synthesis. 4) We also examined the effect of temperature on the diffusion of exogenously delivered material in the extracellular space using autoradiography of the perfused glutamate solution containing ^<14>C-labeled sucrose. The volume of ^<14>C diffusion also increased as brain temperature increased. These results provide evidence that small variations of brain temperature modify glutamate exicitotoxicity, and that hypothermic neuroprotection is exerted by inhibition of the glutamate-induced NO synthesis. The results also suggest that the change in glutamate diffusion in the extracellular space is one mechanism by which mild hypothermia and hyperthermia exert their protective and harmful effects respectively.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Fujisawa H, et al.: "Glutamate neurotoxicity and hypothermia"Journal of Neurotrauma. 15. 10-10 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suehiro E, et al.: "Brain temperature modifies glutamate neurotoxicity in vivo"Journal of Neurotrauma. 16. 285-297 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujisawa H, et al.: "Effects of mild hypothermia on the cortical release of excitatory amino acids and nitric oxide synthesis following hypoxia"Journal of Neurotrauma. 16. 1083-1093 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujisawa H, et al.: "Cerebral blood flow and nitric oxide synthesis -Study using a rat model of transient forebrain ischemia-"Neurotrauma Research. 11. 43-45 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 藤澤博亮ほか: "In vivo brain microdialysisによる脳内一酸化窒素代謝産物測定の有用性と問題点"集中治療. 12. 107-108 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujisawa H, et al.: "Effects of mild hypothermia on glutamate neurotoxicity in vivo : a histological perspective"Neurotrauma Research. 12. 14-19 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujisawa H, et al.: "International Conference on Recent Advances in Neurotraumatology"Chiu W-T, ed. Monduzzi Editore, Bologna. 6 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujisawa H, et al: "Glutamate neurotoxicity and hypothermia"Journal of Neurotrauma. 15. 10 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suehiro E, et al: "Brain temperature modifies glutamate neurotoxicity in vivo"Journal of Neurotrauma. 16. 285-297 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujisawa H, et al: "Effects of mild hypothermia on the cortical release of excitatory amino acids and nitric oxide synthesis following hypoxia"Journal of Neurotrauma. 16. 1083-1093 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujisawa H, et al: "Cerebral blood flow and nitric oxide synthesis -Study using a rat model of transient forebrain ischemia-"Neurotrauma Research. 11. 43-45 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujisawa H, et al: "Measurement of nitric oxide end-products using in vivo brain microdialysis : Its usefulness and problems"Intensive & Critical Care Medicine. 12. 107-108 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujisawa H, et al: "Effects of mild hypothermia on glutamate neurotoxicity in vivo : a histological perspective"Neurotrauma Research. 12. 14-19 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujisawa H, et al: "Sequential changes in excitatory amino acids and nitric oxide synthesis following cerebral hypoxia and effects of mild hypothermia., International Conference on Recent Advances in Neurotraumatology. Chiu W-T, ed. Monduzzi Editore"Bologna. 157-162 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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