Therapy for hyperthermia-induced seizures in Scn1a mutant rats. 2011

Keiichiro Hayashi, and Satoshi Ueshima, and Mamoru Ouchida, and Tomoji Mashimo, and Teiichi Nishiki, and Toshiaki Sendo, and Tadao Serikawa, and Hideki Matsui, and Iori Ohmori
Department of Physiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.

OBJECTIVE 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. RESULTS 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. CONCLUSIONS 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.

UI MeSH Term Description Entries
D008297 Male Males
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D009419 Nerve Tissue Proteins Proteins, Nerve Tissue,Tissue Proteins, Nerve
D011922 Rats, Mutant Strains Rats bearing mutant genes which are phenotypically expressed in the animals. Mutant Strains Rat,Mutant Strains Rats,Rat, Mutant Strains,Strains Rat, Mutant,Strains Rats, Mutant
D001965 Bromides Salts of hydrobromic acid, HBr, with the bromine atom in the 1- oxidation state. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Bromide
D003294 Seizures, Febrile Seizures that occur during a febrile episode. It is a common condition, affecting 2-5% of children aged 3 months to five years. An autosomal dominant pattern of inheritance has been identified in some families. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy (i.e., a nonfebrile seizure disorder) following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy. (From Menkes, Textbook of Child Neurology, 5th ed, p784) Convulsions, Febrile,Febrile Seizures,Pyrexial Seizure,Febrile Convulsion Seizure,Febrile Fit,Fever Convulsion,Fever Seizure,Pyrexial Convulsion,Seizure, Febrile, Complex,Seizure, Febrile, Simple,Convulsion, Febrile,Convulsion, Fever,Convulsion, Pyrexial,Convulsions, Fever,Convulsions, Pyrexial,Febrile Convulsion,Febrile Convulsion Seizures,Febrile Convulsions,Febrile Fits,Febrile Seizure,Fever Convulsions,Fever Seizures,Fit, Febrile,Fits, Febrile,Pyrexial Convulsions,Pyrexial Seizures,Seizure, Febrile,Seizure, Febrile Convulsion,Seizure, Fever,Seizure, Pyrexial,Seizures, Febrile Convulsion,Seizures, Fever,Seizures, Pyrexial
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004569 Electroencephalography Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. EEG,Electroencephalogram,Electroencephalograms
D004829 Epilepsy, Generalized Recurrent conditions characterized by epileptic seizures which arise diffusely and simultaneously from both hemispheres of the brain. Classification is generally based upon motor manifestations of the seizure (e.g., convulsive, nonconvulsive, akinetic, atonic, etc.) or etiology (e.g., idiopathic, cryptogenic, and symptomatic). (From Mayo Clin Proc, 1996 Apr;71(4):405-14) Convulsive Generalized Seizure Disorder,Epilepsy, Tonic,Generalized Nonconvulsive Seizure Disorder,Seizure Disorder, Generalized,Convulsive Seizure Disorder, Generalized,Epilepsy, Akinetic,Epilepsy, Atonic,Generalized Convulsive Epilepsy,Generalized Nonconvulsive Epilepsy,Generalized Onset Seizure Disorder,Generalized Seizure Disorder, Convulsive,Generalized Seizure Disorder, Nonconvulsive,Nonconvulsive Generalized Seizure Disorder,Nonconvulsive Seizure Disorder, Generalized,Seizure Disorder, Convulsive, Generalized,Seizure Disorder, Generalized Nonconvulsive,Seizure Disorder, Generalized Onset,Seizure Disorder, Generalized, Convulsive,Seizure Disorder, Nonconvulsive Generalized,Symptomatic Generalized Epilepsy,Akinetic Epilepsies,Akinetic Epilepsy,Atonic Epilepsies,Atonic Epilepsy,Convulsive Epilepsies, Generalized,Convulsive Epilepsy, Generalized,Epilepsies, Akinetic,Epilepsies, Atonic,Epilepsies, Generalized,Epilepsies, Generalized Convulsive,Epilepsies, Tonic,Epilepsy, Generalized Convulsive,Epilepsy, Generalized Nonconvulsive,Epilepsy, Symptomatic Generalized,Generalized Convulsive Epilepsies,Generalized Epilepsies,Generalized Epilepsy,Generalized Epilepsy, Symptomatic,Generalized Seizure Disorder,Generalized Seizure Disorders,Nonconvulsive Epilepsy, Generalized,Seizure Disorders, Generalized,Tonic Epilepsies,Tonic Epilepsy
D004831 Epilepsies, Myoclonic A clinically diverse group of epilepsy syndromes characterized either by myoclonic seizures or by myoclonus in association with other seizure types. Myoclonic epilepsy syndromes are divided into three subtypes based on etiology: familial, cryptogenic, and symptomatic. Idiopathic Myoclonic Epilepsy,Myoclonic Absence Epilepsy,Myoclonic Encephalopathy,Myoclonic Epilepsy,Symptomatic Myoclonic Epilepsy,Benign Infantile Myoclonic Epilepsy,Cryptogenic Myoclonic Epilepsy,Doose Syndrome,Dravet Syndrome,Early Childhood Epilepsy, Myoclonic,Early Childhood, Myoclonic Epilepsy,Encephalopathy, Myoclonic,Epilepsy, Early Childhood, Myoclonic,Epilepsy, Myoclonic, Early Childhood,Epilepsy, Myoclonic, Infantile,Epilepsy, Myoclonic, Infantile, Benign,Epilepsy, Myoclonic, Infantile, Severe,Epilepsy, Myoclonus,Infantile Severe Myoclonic Epilepsy,Myoclonic Astatic Epilepsy,Myoclonic Epilepsy, Benign Infantile,Myoclonic Epilepsy, Early Childhood,Myoclonic Epilepsy, Infantile,Myoclonic Epilepsy, Infantile, Benign,Myoclonic Epilepsy, Infantile, Severe,Myoclonic Epilepsy, Severe Infantile,Myoclonic Epilepsy, Severe, Of Infancy,Myoclonic Seizure Disorder,Severe Infantile Myoclonic Epilepsy,Severe Myoclonic Epilepsy Of Infancy,Severe Myoclonic Epilepsy, Infantile,Astatic Epilepsies, Myoclonic,Astatic Epilepsy, Myoclonic,Cryptogenic Myoclonic Epilepsies,Dravet Syndromes,Encephalopathies, Myoclonic,Epilepsies, Cryptogenic Myoclonic,Epilepsies, Idiopathic Myoclonic,Epilepsies, Infantile Myoclonic,Epilepsies, Myoclonic Absence,Epilepsies, Myoclonic Astatic,Epilepsies, Symptomatic Myoclonic,Epilepsy, Cryptogenic Myoclonic,Epilepsy, Idiopathic Myoclonic,Epilepsy, Infantile Myoclonic,Epilepsy, Myoclonic,Epilepsy, Myoclonic Absence,Epilepsy, Myoclonic Astatic,Epilepsy, Symptomatic Myoclonic,Idiopathic Myoclonic Epilepsies,Infantile Myoclonic Epilepsies,Infantile Myoclonic Epilepsy,Myoclonic Absence Epilepsies,Myoclonic Astatic Epilepsies,Myoclonic Encephalopathies,Myoclonic Epilepsies,Myoclonic Epilepsies, Cryptogenic,Myoclonic Epilepsies, Idiopathic,Myoclonic Epilepsies, Infantile,Myoclonic Epilepsies, Symptomatic,Myoclonic Epilepsy, Cryptogenic,Myoclonic Epilepsy, Idiopathic,Myoclonic Epilepsy, Symptomatic,Myoclonic Seizure Disorders,Myoclonus Epilepsies,Myoclonus Epilepsy,Seizure Disorder, Myoclonic,Seizure Disorders, Myoclonic,Symptomatic Myoclonic Epilepsies

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