Current affiliations of Drs. Kabovi and PometlovB: Department of Normal, Clinical and Pathological Physiology, Third Faculty of Medicine, Charles University, Praha, Czech Republic.
Age-Specific N-Methyl-D-Aspartate—Induced Seizures: Perspectives for the West Syndrome Model
Version of Record online: 2 AUG 2005
Volume 40, Issue 10, pages 1357–1369, October 1999
How to Cite
Kábová, R., Liptáková, S., Šlamberová, R., Pometlová, M. and Velíšek, L. (1999), Age-Specific N-Methyl-D-Aspartate—Induced Seizures: Perspectives for the West Syndrome Model. Epilepsia, 40: 1357–1369. doi: 10.1111/j.1528-1157.1999.tb02006.x
Present affiliation of Drs. Liptáková and Velíšek: Departments of Neurology; of Dr. Slamberová: Psychiatry; and of Dr. Velíšek: Neuroscience, Albert Einstein College of Medicine, Bronx, New York, U.S.A.
- Issue online: 2 AUG 2005
- Version of Record online: 2 AUG 2005
- Accepted April 6, 1999.
- West syndrome;
Summary: 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.