The effects of responsive and scheduled subicular high frequency stimulation in the intra-hippocampal kainic acid seizure model

BACKGROUND Responsive stimulation is a promising and newly emerging treatment for refractory temporal lobe epilepsy in which current is delivered to target areas following seizure occurrence. OBJECTIVE We compared responsive and scheduled subicular high frequency stimulation (HFS) with a sham control group on acute seizures and seizure sensitivity two weeks later. We also investigated the role of status epilepticus (SE) on efficacy of both types of stimulation. METHOD Adult Wistar rats received kainic acid (KA) injections intrahippocampally until they reached Stage V (Racine scale) on Day 1. Responsive, scheduled or sham HFS (125 Hz, 100 μs) was delivered in three groups while EEG was recorded. All rats received KA injections again on Day 15 to measure the excitability of animals to KA, again with EEG monitoring. RESULTS All rats reached Stage V and 60% reached SE on Day 1. Focal seizures were suppressed in both stimulated groups (the scheduled group was slightly more effective) on both days in only non-SE rats. Similar stimulation effects were found on generalized seizures but mainly on Day 15. CONCLUSION Both types of subicular HFS suppressed focal and generalized seizures, albeit differently. Scheduled stimulation seemed a bit more effective, and the amount of stimulation might be a factor that influences the differences between the stimulated groups. Beneficial effects of HFS were restricted to non-SE rats and HFS did not suppress or even worsen seizures in SE rats.

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