Age-specific N-methyl-D-aspartate-induced seizures: Perspectives for the West syndrome model

Purpose: With intraperitoneal N-methyl-D-aspartate (NMDA; 15-200 mg/kg) adm inistration, we attempted to develop an animal model of age-specific West s yndrome to serve for testing of putative anticonvulsant drugs and to determ ine the mechanisms of this disorder. Methods: Experiments were performed in 12-, 18-, and 60-day-old (adult) rat s. The effects of systemic pretreatment with hydrocortisone (5-25 mg/kg), p yridoxine (20-250 mg/kg), and sodium valproate (VPA; 200 and 400 mg/kg) aga inst the NMDA-induced automatisms, emprosthotonic (hyperflexion), and cloni c-tonic seizures were determined. NMDA-induced EEG changes and alterations of the performance in horizontal bar, rotorod, open field, and elevated plu s-maze tests were recorded. Results: In young rats, hydrocortisone had proconvulsant effects. High dose s of pyridoxine induced epileptiform activity independent of and distinct f rom that induced by NMDA, Only VPA had moderate effects against the NMDA-in duced syndrome. EEG consisted of periods of suppression mixed with ictal ac tivity of serrated waves and high-voltage chaotic EEG activity. In adult ra ts, EEG alterations involved spike and spike-and-wave activity. NMDA also d eteriorated performance of young rats in the open field, rotorod, and eleva ted plus maze tests. Conclusions: NMDA syndrome in rats fulfills some, but not all, criteria of the West syndrome model, such as occurrence of flexion seizures, nonspecifi c diffuse EEG changes, refractoriness to antiepileptic therapy (but a respo nse to VPA), as well as long-term alteration of behavioral Casks. However, NMDA-induced seizures represent an acute model without the occurrence of sp ontaneous seizures, whereas in the clinical situation, both the seizures an d neurologic deterioration are chronic. Further, in the West syndrome and t he NMDA seizure model, there is an incongruent response to therapy with ant iepileptic drugs.