Therapy for hyperthermia-induced seizures in Scn1a mutant rats

Keiichiro Hayashi, Satoshi Ueshima, Mamoru Ouchida, Tomoji Mashimo, Teiichi Nishiki, Toshiaki Sendo, Tadao Serikawa, Hideki Matsui, Iori Ohmori

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15 Citations (Scopus)

Abstract

Mutations in the SCN1A gene, which encodes the α1 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°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.

Original languageEnglish
Pages (from-to)1010-1017
Number of pages8
JournalEpilepsia
Volume52
Issue number5
DOIs
Publication statusPublished - May 2011

Keywords

  • Animal models
  • Febrile seizure
  • Generalized epilepsy with febrile seizures plus
  • Scn1a gene
  • Severe myoclonic epilepsy of infancy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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  • Cite this

    Hayashi, K., Ueshima, S., Ouchida, M., Mashimo, T., Nishiki, T., Sendo, T., Serikawa, T., Matsui, H., & Ohmori, I. (2011). Therapy for hyperthermia-induced seizures in Scn1a mutant rats. Epilepsia, 52(5), 1010-1017. https://doi.org/10.1111/j.1528-1167.2011.03046.x