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2002 Fiscal Year Final Research Report Summary

Brain protection from the neuronal death induced by spreading depression

Research Project

Project/Area Number 13671612
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionKyorin University

Principal Investigator

IIJIMA Takehiko  Kyorin University, School of Medicine, Associate Professor, 医学部, 助教授 (10193129)

Co-Investigator(Kenkyū-buntansha) MISHIMA Tatsuya  Kyorin University, School of Medicine, Assistant, 医学部, 助手 (40317095)
Project Period (FY) 2001 – 2002
KeywordsCerebral ischemia / Mitochondria / Menbrane potential / Glutathione / Reactive nitrogen species / reperfusion injury / spreading depression / microdialysis
Research Abstract

We have accomplished two projects supported by this grant. First, we examined radical formation and radical scavenging during reperfusion period after ischemia. Second, we examined mitochondrial membrane potential during reoxygenation after oxygen-glucose deprivation. The first project suggested physiological protective mechanism of neuron from toxic effect of free radical during early reperfusion phase. Therefore, we moved to mitochondrial mechanism involved in active neuronal suicide, apoptosis because active neuronal death executed by neuron itself seems to be a main cause of neuronal damage after ischemia.
1. The role of glutathione during reperfusion
A timed profile of glutathione oxidation and reactive nitrogen species during reperfusion after cerebral ischemia in rat was obtained. GSH and GSSG increased and reached a peak; 3408 ^^+__-1710% (mean ^^+__- SE) at 25 min of reperfusion (P<0.0001); and 329 ^^+__- 104% at 50 min of reperfusion (p=0.06), respectively. NO_2 levels did not significantly change. These data suggest that GSH releases during early phase of reperfusion and its rapid oxidation contributes to prevent increase in reactive nitrogen species.
2. Involvement of mitochondrial mechanism for ischemic neuronal death
A primary hippocampal culture seeded in a 35mm fenestrated dish for fluorescence microscopy was mounted in a sealed chamber for an anaerobic incubation (oxygen-glucose deprivation (OGD)). During OGD, MMP decreased to 0.72 ^^+__- 0.03 (normalized JC-1 fluorescence), then increased to the hyperpolarized level 1.99 ^^+__- 0.12 during 60min reoxygenation after 30 min OGD. After 90 min OGD and reoxygenation, MMP was reduced and never recovered. The intracellular ATP content was 8.1 ^^+__- 6.6% and 3.2 ^^+__- 1.9% after 30 mm OGD and 30 min reoxygenation following 30 min OGD, respectively. This observation suggests the inhibition of electron reentry into an inner membrane during reoxygenation and the disturbance of F_0F_1-ATP synthase.

  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Iijima T, MishimaT, Tohyama M, Akagawa K, Iwao Y: "Mitochondrial membrane potential and intracellular ATP content after transient experimental ischemia in the cultured hippocampal neuron"Neurochemistry International. 43(3). 263-269 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iijima T, Sakamoto H, Okada C, Iwao Y: "Relationship between oxidation of glutathione and reactive nitrogen species during the early-reperfusion phase of cerebral ischemia"Neurochemistry Research. 27(6). 497-500 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 飯島毅彦, 三嶋竜弥, 赤川公朗, 比嘉正祐, 巌康秀: "培養細胞におけるミトコンドリア膜電位の虚血時の変化-プロポフォールの影響-"Pharmacoanesthesiology. 13(2). 112-115 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 飯島毅彦, 三嶋竜弥, 赤川公朗, 巌康秀: "培養細胞におけるミトコンドリア膜電位の虚血時の変化"脳循環代謝. 13(3). 156-157 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iijima T., Sakamoto H., Okada C., and Iwao Y.: "Relationship between oxidation of glutathione and reactive nitrogen species during the early-reperfusion phase of cerebral ischemia"Neurochem Res. 27(6). 497-500 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iijima T., Mishima T., Tohyama M., Akagawa K., Iwao Y.: "Mitochondrial membrane potential and intracellular ATP content after transient experimental ischemia in the cultured hippocampal neuron"Neurochem Int. 43(3). 263-269 (2003)

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

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Published: 2004-04-14  

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