GABA Regulates Stem Cell Proliferation before Nervous System Formation

2008 Epilepsy Currents  
A New Animal Model of Infantile Spasms with Unprovoked Persistent Seizures. Lee CL, Frost JD Jr, Swann JW, Hrachovy RA. Epilepsia 2008;49(2):298-307. PURPOSE: Infantile spasms is one of the most severe epileptic syndromes of infancy and early childhood. Progress toward understanding the pathophysiology of this disorder and the development of effective therapies has been hindered by the lack of a relevant animal model. We report here the creation of such a model. METHODS: The sodium channel
more » ... er, tetrodotoxin (TTX), was chronically infused into the developing neocortex or hippocampus of infant rats by way of an osmotic minipump starting on postnatal day 10-12. RESULTS: After a minimum of 10 days of infusion, approximately one-third of these rats began to display very brief (1-2 s) spasms, which consisted of symmetric or asymmetric flexion or extension of the trunk and sometimes involvement of one or both forelimbs. The typical ictal EEG pattern associated with the behavioral spasms consisted of an initial generalized, high amplitude, slow wave followed by an electrodecrement with superimposed fast activity. The interictal EEG revealed multifocal spikes and sharp waves, and in most animals that had spasms a hypsarrhythmic pattern was seen, at least intermittently, during NREM sleep. Like in humans, the spasms in the rat often occurred in clusters especially during sleep-wake transitions. Comparison of the ictal and interictal EEGs recorded in this model and those from humans with infantile spasms revealed that the patterns and the frequency components of both the ictal events and hypsarrhythmia were very similar. DISCUSSION: The TTX model of infantile spasms should be of value in furthering an understanding of the pathophysiology of this seizure disorder.
doi:10.1111/j.1535-7511.2008.00270.x pmid:18852839 pmcid:PMC2566617 fatcat:bhtdypuqurfi3e7s7lvgutf3cm