Abstracts

Rationale: Despite the clinical observation that in infants and children seizures are more likely to begin in the neocortex than hippocampus, there have been no systematic studies of the long-term consequences of early life seizures on neocortical excitability. The purpose of the present study was to examine the effect of flurothyl-induced seizures during the neonatal period on neocortical excitability of the mature brain. Methods: Young and adult Sprague-Dawley rats were used throughout the study. The flurothyl model of neonatal seizures was used. Rats were exposed to convulsant doses of flurothyl 6 times per day for 10 days beginning at postnatal day (P) 1. Extracellular field potentials were recorded by glass electrodes from sagittal brain slices simultaneously from layer 2 and layer 3/4 of somatosensory cortex in both P20-25 and adult (>P120) rats. Seizure-like activity (SLA) was evoked by application of different concentrations of inhibitory synaptic transmission antagonists bicuculline and gabazine. Results: Seizures susceptibility of somatosensory cortex slices was assessed from young and adult rats with a prior history of neonatal seizures along with age-matched controls. We analyzed delay of seizures-like activity (SLA) onset along with frequency, duration and amplitude of SLA. We found a significant increase in probability of SLA induction by bicuculline and gabazine in both young and adult flurothyl rats compared to controls. SLA induced by bicuculline and gabazine were significantly delayed in slices from control rats vs. flurothyl rats. In addition, we found a significant increase in frequency and duration of SLA evoked by application 1 mkM gabazine in flurothyl rats compared to controls. The amplitude of SLA was not significantly different in the two studied groups.Conclusions: Our results indicate that neonatal seizures result in persistent alterations in neocortical excitability as evidenced by an enhancement susceptibility to seizure-like activity with GABAA blockers when compared to control animals. Our study suggests that neonatal seizures permanently alter the balance of excitation and inhibition in the neocortex. (Supported by NIH Grant numbers: NS41595 and NS44296, and NATO Science Programme)