West syndrome model: seek and you will find.
West syndrome is an age-specific epileptic syndrome with onset in infancy. It comprises infantile spasms (usually flexion convulsions), EEG pattern of hypsarrhythmia and mental retardation. Current therapy involves ACTH, corticosteroids, valproic acid, pyridoxine and vigabatrine. The treatment is difficult and more effective antiepileptic drugs are required. Unfortunately, there is no animal model of West syndrome that would accurately depict the situation found in humans. N-methyl-D-asparate (NMDA)-induced seizures in infant rats have certain features of the West syndrome model. These seizures are age-specific (they occur before 25 days of age), include hyperflection (emprosthotonus), their EEG is not specific and they somewhat respond to treatment with the benzodiazepine clonazepam. In 12 and 18 day old rats, we tested the effects of hydrocortisone, pyridoxine and sodium valproate against the seizures induced by 15 and 45 mg/kg of NMDA i.p., respectively. There were weak effects of sodium valproate against the NMDA-induced emprosthotonus. In contrast, high doses of pyridoxine were proconvulsant and hydrocortisone worsened the damage of nerve cells induced by NMDA. The data show that NMDA-induced seizures although similar to West syndrome are extremely resistant to therapy and may not be a good model of the West syndrome. However, the search for an adequate model that would allow for determination of possible mechanisms and testing of putative antiepileptic drugs will continue.
Kábová
R
R
Department of Pathological Physiology, Third Faculty of Medicine, Charles University Prague, Czech Republic.
Veresová
S
S
Velísek
L
L
D000818:Animals; D004195:Disease Models, Animal; D004569:Electroencephalography; D018691:Excitatory Amino Acid Antagonists; D006801:Humans; D007223:Infant; D016202:N-Methylaspartate; D051381:Rats; D013036:Spasms, Infantile / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology
D018691:Excitatory Amino Acid Antagonists; D016202:N-Methylaspartate