1988 Fiscal Year Final Research Report Summary
Development of epileptic model animals and evaluating methods for antiepileptic drugs and its application.
| Project/Area Number |
62300010
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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 |
広領域
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| Research Institution | Kyoto University |
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Principal Investigator |
TAKAORI Shuji Kyoto University, Faculty of Medicine, Professor, 医学部, 教授 (10025538)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Akitane Okayama University, Medical School, Professor, 医学部, 教授 (20028434)
FUKUDA Takeo Kagoshima University, Faculty of Medicine, Professor, 医学部, 教授 (70038694)
KIMISHIMA Kenjiro Tottori University School of Medicine, Professor, 医学部, 教授 (70031945)
FUKUDA Hideomi University of Tokyo, Faculty of Pharmaceutical Sciences, Professor, 薬学, 教授 (50080172)
YAMADA Junzo Kyoto University, Faculty of Medicine, Professor, 医学部, 教授 (90025651)
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| Project Period (FY) |
1987 – 1988
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| Keywords | epilepsy / antiepileptic drugs / model animal / spontaneously epileptic rat (SER) kindling / E1 mouse / phenobarbital / フェノバルビタール / バルプロ酸 |
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| Research Abstract |
Genetical background, neuropthaological and biochmical changes and pharmacological usefulness were examined in the spontaneously epileptic rat (SER) which is an epileptic model animal showing both tonic convulsion and absence-like seizures and compared with those of other genetically defined or artificially induced epilepsy model animals in cooperation with investigators. In addition, the methods for evaluation of antiepileptic drugs were studied using varieties of epilepsy model aninals. Takaori found that continual intake of phenobarbital inhibited tonic convulsion but not absence-like seizures in SER, corresponding the effects of the drug on human epilepsy. Then, acnormality of brain catecholamine level was detected in the SER and zitter rat, compared with Kyoto-Wistar and tremor rats. Yamada established the position of 38 labeled genes in SER and found that absence-like seizure was semi-dominantly induced by tm gene. Tateishi found that there were diffuse vacuole formation in extra
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cellular space and hypomyelination in SER central nervous system but nerve cells were intact. In El mouse, another epileptic model, Suzuki found that seizure discharges originated in parietal cortex propagated into hippocampus, and then clarified the significance of GABA in inducing seizures in this animal since GAD activity was decreased in cerebral cortex and increased in hippocaupus. Sato demonstrated that kindling phenomenon was in rat was useful in evaluating antiepileptic drugs, and provided the principle of the evaluation by raising progabide as examples. Usefulness of pentylentetrazol-induced kinkling in evaluating drugs for absence epilepsy was demonstrated by Kimijima. Takeo Fukuda showed that myoclonus induced by vatramine and a ratio of tonic extension to tonic flection in electroconvulsive seizure are useful in evaluating the drugs for myoclonus and tonic-clonic convulsion epilepsies, respectively. Evaluation of antiepileptic drugs was found by Hideomi Fukuda to be done according to the effects on post-tetanic potentiation in amygdala-pyriform slice preparation but not on spinal post-tetanic potentiation. Mori found that glutamate antagonists (AP5, CPP etc.) did not always inhibit the seizure in El mouse but GABA related drugs were effective in inhibiting the seizure, while CPP induced the epileptic seizure in normal rat. Less
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