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ID 52802
FullText URL
Author
Hayashi, Keiichiro
Ueshima, Satoshi
Mashimo, Tomoji
Sendo, Toshiaki Kaken ID researchmap
Serikawa, Tadao
Ohmori, Iori
Abstract
Purpose: Mutations in the SCN1A gene, which encodes the alpha 1 subunit of voltage-gated sodium channels, cause generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI). N1417H-Scn1a mutant rats are considered to be an animal model of human FS+ or GEFS+. To assess the pharmacologic validity of this model, we compared the efficacies of eight different antiepileptic drugs (AEDs) for the treatment of hyperthermia-induced seizures using N1417H-Scn1a mutant rats. Methods: AEDs used in this study included valproate, carbamazepine (CBZ), phenobarbital, gabapentin, acetazolamide, diazepam (DZP), topiramate, and potassium bromide (KBr). The effects of these AEDs were evaluated using the hot water model, which is a model of experimental FS. Five-week-old rats were pretreated with each AED and immersed in water at 45 degrees C to induce hyperthermia-induced seizures. The seizure manifestations and video-electroencephalographic recordings were evaluated. Furthermore, the effects of each AED on motor coordination and balance were assessed using the balance-beam test. Key Findings: KBr significantly reduced seizure durations, and its anticonvulsant effects were comparable to those of DZP. On the other hand, CBZ decreased the seizure threshold. In addition, DZP and not KBr showed significant impairment in motor coordination and balance. Significance: DZP and KBr showed potent inhibitory effects against hyperthermia-induced seizures in the Scn1a mutant rats, whereas CBZ exhibited adverse effects. These responses to hyperthermia-induced seizures were similar to those in patients with GEFS+ and SMEI. N1417H-Scn1a mutant rats may, therefore, be useful for testing the efficacy of new AEDs against FS in GEFS+ and SMEI patients.
Keywords
Febrile seizure
Animal models
Scn1a gene
Generalized epilepsy with febrile seizures plus
Severe myoclonic epilepsy of infancy
Published Date
2011-05
Publication Title
Epilepsia
Volume
volume52
Issue
issue5
Start Page
1010
End Page
1017
ISSN
0013-9580
Content Type
Journal Article
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/52526
language
英語
File Version
author
Refereed
True
DOI
Web of Science KeyUT