2002 Fiscal Year Final Research Report Summary
Characteristics of flurothyl-induced seizures and the evaluation of the model of development of epilepsy
| Project/Area Number |
13672388
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Ehime University (2002)
Okayama University (2001) |
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Principal Investigator |
ARAKI Hiroaki Ehime University Hospital, Professor, 医学部附属病院, 教授 (50294450)
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| Co-Investigator(Kenkyū-buntansha) |
GOMITA Yutaka Okayama University Hospital, Professor, 医学部附属病院, 教授 (00088709)
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| Project Period (FY) |
2001 – 2002
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| Keywords | flurothyl / kindling / MK-801 / Mongolian gerbils / Electroencephalogram / antiepileptic drugs |
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| Research Abstract |
1) In the flurothyl kindling model, eight flurothyl-induced generalized clonic seizures, dubbed forebrain seizures, and a subsequent 28-days stimulation-free interval changed the seizure phenotype of mice from purely forebrain seizure to seizures of a more complex phenotype. The generalized-onset, forebrain seizure progresses rapidly to a seizure with tonic manifestations, dubbed brain-stem seizures, when re-challenged with flurothyl.
2) When valproate, zonisamide and phenytoin were administered to mice daily for 8 d prior to the flurothyl trial changes in the seizure phenotype from clonic to tonic seizure were significantly inhibited by valproate and zonisamide, but not by phenytoin.
3) In the acute effect of MK-801 in naive and flurothyl-kindled mice, there were no changes on the latencies of clonic seizures. However, MK-801 dose-dependently inhibited both latencies and the incidence of tonic seizures in mice and suppressed the grade of seizure severity in flurothyl-kindled mice. In addition, repeated administration of MK-801 did not have any effect on the latencies of clonic seizure. However, seizure severity was significantly exacerbated when mice were re-exposed to flurothyl without MK-801 1 week after the last administration.
4) Mongolian gerbils demonstrated tonic extension immediately after within 1 min after the appearance of clonic convulsion. Very high amplitude spike waves appeared in the cortex, hippocampus and amygdala concurrent with the appearance of clonic convulsion.
5) The epilepsy pattern was not changed in 6-OHDA- and DSP-4-administered mice. This finding is completely different with electrical kindling model.
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