Abstracts

RATIONALE: We sought to investigate mechanisms underlying seizure spread and termination by examining evoked responses during seizures in naturally epileptic gerbils. METHODS: Gerbils (n=18) were implanted with 25 ?m diameter wire in the dentate gyrus and a screw over the ipsilateral neocortex. A stimulating electrode activated the perforant path with paired-pulses (0.2 Hz, 15 ms interval). Evoked responses were obtained during seizures triggered by novel environment exposure. Population spike amplitude and amplitude ratio (2nd/1st spike) were analyzed. RESULTS: Behaviorally seizures range from brief immobility to severe generalized convulsions. In adults 23 seizures were recorded, 87% with generalized convulsions. For an average of 20 s after EEG seizure onset, population spike amplitude increases, multiple spikes are evoked, spontaneous spikes appear, and amplitude ratio increases indicating reduced paired-pulse inhibition. Flatline responses follow for 29 ? 3 s (mean ? sem). EEG seizure activity terminates 13 ? 2 s after flatline period onset. Spike amplitude recovers over the next 60 s to 60-80% of baseline value, and amplitude ratio decreases correspondingly. The switch from immobility to resumption of normal behavior is abrupt and coincident with an increase in spike amplitude from 77 to 101% of baseline. In juvenile gerbils 40 seizures were recorded, 43% consisted of brief immobility without severe generalized convulsions. Electrophysiologically seizures and evoked responses in juveniles are similar to adults but less severe. Differences include an increase in spike amplitude to 1.53 times baseline within 5 s before EEG seizure onset and lack of a flatline period and multiple evoked spikes during the seizure. CONCLUSIONS: These findings suggest: 1 Seizures are more severe in adults vs juveniles, possibly due to recurrent seizures or gradual expression of the inherited pathogenesis. 2 Seizure-induced immobility correlates with depressed responsiveness to afferent stimulation. 3 EEG seizure activity persists after the tissue fails to respond to stimulation, raising questions about the seizure mechanism. Supported by Burroughs Wellcome Fund.