| Project/Area Number |
04557123
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
SASA Masashi Professor, Hiroshima University School of Medicine, 医学部, 教授 (20025654)
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| Co-Investigator(Kenkyū-buntansha) |
SERIKAWA Tadao Professor, Faculty of Medicine, Kyoto University, 医学部, 教授 (30025655)
MATSUBAYASHI Hiroaki Research Associate, Hiroshima University School of Medicine, 医学部, 助手 (60165850)
山田 淳三 京都大学, 医学部, 教授 (90025651)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1993: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1992: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | Tremor rat / Absence-like seizure / Spontaneously epileptic rat(SER) / Antiepileptics / Hippocampal pyramidal cell / Ca^<2+> channel / TRH |
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| Research Abstract |
Studies were performed to establish production and maintenance of newly found tremor rat (tm/tm) that showed absence-like seizures and the pharmacological usefulness of this animal.
(1) The possible focus that shows spikes and wave complex in EEG was found in left hippocampal CA3 field in the young tremor rat, and then the spike and wave complex developed to bilateral corteces and right hippocampal CA3 area with aging.
(2) The profile of the conventional antiepileptic drugs on the absence-like seizures was similar to that on human absence seizures, as in spontaneously epileptic rat (SER) : The seizure was inhibited by ethosuximide, trimethadione, valproate and phenobarbital, but not by phenytoin.
(3) In hippocampal slice preparation, long-lasting depolarization shift accompanying repetitive firing was induced by a single stimulation of the mossy fiber in CA3 pyramidal cells. The response was inhibited by Ca^<2+> antagonist, nicardipine, suggesting that there is an enhancement of Ca^<2+> current in hippocampal CA3 pyramidal cells probably due to Ca^<2+> channel abnormality.
(4) Ca^<2+> current sensitive to nicardipine was obtained using acutely dissociated hippocampal cells.
These results imply that tremor rat is useful for evaluation of the acute and chronic effects of antiepileptics and study on the mechanism underlying the absence-like seizures.
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