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Therapy for hyperthermia‐induced seizures in Scn1a mutant rats
Author(s) -
Hayashi Keiichiro,
Ueshima Satoshi,
Ouchida Mamoru,
Mashimo Tomoji,
Nishiki Teiichi,
Sendo Toshiaki,
Serikawa Tadao,
Matsui Hideki,
Ohmori Iori
Publication year - 2011
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2011.03046.x
Subject(s) - carbamazepine , epilepsy , anesthesia , anticonvulsant , hyperthermia , medicine , diazepam , pharmacology , phenobarbital , motor coordination , topiramate , psychiatry
Summary Purpose: 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‐ Scn1 a mutant rats may, therefore, be useful for testing the efficacy of new AEDs against FS in GEFS+ and SMEI patients.