Age-specific N-methyl-D-aspartate-induced seizures: perspectives for the West syndrome model
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Behavior, Animal drug effects MeSH
- Electroencephalography drug effects statistics & numerical data MeSH
- Hydrocortisone pharmacology therapeutic use MeSH
- Spasms, Infantile chemically induced diagnosis prevention & control MeSH
- Rats MeSH
- Valproic Acid pharmacology therapeutic use MeSH
- Humans MeSH
- Disease Models, Animal * MeSH
- N-Methylaspartate * pharmacology MeSH
- Pyridoxine pharmacology therapeutic use MeSH
- Age Factors MeSH
- Seizures chemically induced diagnosis prevention & control MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Hydrocortisone MeSH
- Valproic Acid MeSH
- N-Methylaspartate * MeSH
- Pyridoxine MeSH
PURPOSE: With intraperitoneal N-methyl-D-aspartate (NMDA; 15-200 mg/kg) administration, we attempted to develop an animal model of age-specific West syndrome to serve for testing of putative anticonvulsant drugs and to determine the mechanisms of this disorder. METHODS: Experiments were performed in 12-, 18-, and 60-day-old (adult) rats. The effects of systemic pretreatment with hydrocortisone (5-25 mg/kg), pyridoxine (20-250 mg/kg), and sodium valproate (VPA; 200 and 400 mg/kg) against the NMDA-induced automatisms, emprosthotonic (hyperflexion), and clonic-tonic seizures were determined. NMDA-induced EEG changes and alterations of the performance in horizontal bar, rotorod, open field, and elevated plus-maze tests were recorded. RESULTS: In young rats, hydrocortisone had proconvulsant effects. High doses of pyridoxine induced epileptiform activity independent of and distinct from that induced by NMDA. Only VPA had moderate effects against the NMDA-induced syndrome. EEG consisted of periods of suppression mixed with ictal activity of serrated waves and high-voltage chaotic EEG activity. In adult rats, EEG alterations involved spike and spike-and-wave activity. NMDA also deteriorated performance of young rats in the open field, rotorod, and elevated 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, nonspecific diffuse EEG changes, refractoriness to antiepileptic therapy (but a response to VPA), as well as long-term alteration of behavioral tasks. However, NMDA-induced seizures represent an acute model without the occurrence of spontaneous seizures, whereas in the clinical situation, both the seizures and neurologic deterioration are chronic. Further, in the West syndrome and the NMDA seizure model, there is an incongruent response to therapy with antiepileptic drugs.
References provided by Crossref.org
