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ID 52802
フルテキストURL
著者
Hayashi, Keiichiro Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Physiol
Ueshima, Satoshi Okayama Univ Hosp, Dept Pharm
Ouchida, Mamoru Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Genet 科研費研究者番号
Mashimo, Tomoji Kyoto Univ, Grad Sch Med, Inst Lab Anim
Nishiki, Teiichi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Physiol 科研費研究者番号
Sendo, Toshiaki Okayama Univ Hosp, Dept Pharm
Serikawa, Tadao Kyoto Univ, Grad Sch Med, Inst Lab Anim
Matsui, Hideki Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Physiol
Ohmori, Iori Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Physiol
抄録
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.
キーワード
Febrile seizure
Animal models
Scn1a gene
Generalized epilepsy with febrile seizures plus
Severe myoclonic epilepsy of infancy
発行日
2011-05
出版物タイトル
Epilepsia
52巻
5号
開始ページ
1010
終了ページ
1017
ISSN
0013-9580
資料タイプ
学術雑誌論文
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/52526
言語
English
論文のバージョン
author
査読
有り
DOI
Web of Sience KeyUT