[A novel epilepsy animal model (NER)].
A mutant showing convulsive seizures spontaneously in a CJ: Wistar colony was named the Noda epileptic rat (NER). The NER exhibits tonic-clonic convulsion without any external stimuli once every 30 h. However, we succeeded in inducing similar convulsive seizures by applying priming sound stimuli (95 dB, 8 kHz, 30 sec) from 3 weeks of age in all 24 NER examined. When the effects of clinically available antiepileptics were tested on the seizures of such primed NER, the most potent agents were carbamazepine, diazepam, valproate, phenobarbital and trimethadione, while phenytoin and zonisamide showed lower potency. Furthermore, ethosuximide was not effective in inhibiting the seizures. In hippocampal slices of NER with convulsive seizures, repetitive firing accompanied by long-lasting depolarization was observed when a single stimulation was delivered to the mossy fibers in the CA3 pyramidal cell. This depolarization shift was completely blocked with a Ca2+ antagonist (nicardipine 10 nM). The long-lasting hyperpolarization that followed the repetitive firing was also observed with mossy fiber stimulation in the hippocampal CA3 pyramidal cells of the NER. These findings suggest that Ca2+ channel abnormality of the hippocampal CA3 pyramidal cells may be involved in the convulsive seizures.
Sasa
M
M
Department of Pharmacology, Hiroshima University School of Medicine, Japan.
Hanaya
R
R
Iida
K
K
Akimitsu
T
T
Kurisu
K
K
Noda
A
A
Serikawa
T
T
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy; D006624:Hippocampus / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains
D000927:Anticonvulsants