| Project/Area Number |
04304042
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
麻酔学
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| Research Institution | Niigata University |
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Principal Investigator |
SHIMOJI Koki Niigata University School of Medicine Professor, 医学部, 教授 (30040158)
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| Co-Investigator(Kenkyū-buntansha) |
HIGASHI Hideho Kurume University School of Medicine Professor, 医学部, 教授 (10098907)
SATOH Masamichi Kyoto University Faculty of Pharmacy Professor, 薬学部, 教授 (80025709)
KUMANISHI Toshiro Niigata University Brain Research Institute Professor, 脳研究所, 教授 (40018601)
ASANO Takao Saitama Medical School Medical Center Professor, 総合医療センター, 教授 (70090496)
AKAIKE Norio Kyushu University School of Medicine Professor, 医学部, 教授 (30040182)
崎村 建司 新潟大学, 脳研究所, 助教授 (40162325)
佐武 明 新潟大学, 脳研究所, 教授 (70018589)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 1994: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1993: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1992: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | Brain ischemia / Intracellular calcium / Long term potentiation / Calcium channel / NMDA receptor / Calcium binding protein / cDNA subtraction / Nitric oxide / NMDAレセプタ / NO / アラキドン酸代謝系 / 海馬スライス / 脳損傷 / 海馬 |
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| Research Abstract |
(1)Increase in [Ca^<2+>] _i in response to oxygen-glucose deprivation was inhibited in mechanically injured hippocampal slices in comparison with non-injured slices 1-3 days after the injury. The fact suggests that intrinsic anti-ischemic activity may be induced in the vicinity of the injury. (2)Irreversible neuronal changes may be produced at 1-1.5 minfollowing a rapid depolarization of membrane potential induced by oxygen-glucose deprivation. Both Ca^<2+>-influx through NMDA receptor channels and Ca^<2+>release from intracellular site may associate the irreversible neuronal changes. (3) Mild acidosis inhibited both of increases in [Ca^<2+>] _i and membrane depolarization of hippocampal neurons in response to oxygen-glucose deprivation. (4)Active changes in [Ca^<2+>] _i in glial cells indicate important roles of glia for induction of LTP and ischemic changes in neurons.(5)LTP in hippocampal mossy fiber-CA3 synaps was suggested to be induced presynaptically. (6)Voltage-gated calcium channels contributing to release of chemical transmitters in hippocampus are assigned to be P-and L-type high threshold calcium channels but not to N-type calcium channels. (7)The molecular structure of subtypes composing the NMDA receptors was determined. Different distributions of each subtype may relate to vulnerability of neurons to ischemic damage. (8)Calcium binding proteins associating with neurotransmitter release from presynaptic membrane were determined. These proteins may associate with receptor-mediated intracellular signal transductions. (9)To assess unknown gene family induced by ischemia, new and high-sensitive cDNA subtraction method "directional tag PCR subtraction" was developed. (10)Nitric oxide synthase inhibitor reduced the infarction area. Inhibitors of the arachidonic acid metabolism inhibited the irreversible neuronal depolarization in hippocampal slices.
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