Abstracts

Rationale: Kainic-acid-induced status epilepticus is a popular animal model of temporal lobe epilepsy (TLE). Previous electrographic recordings of seizures induced by intraperitoneal kainic acid (KA) injections have focused on hippocampal monitoring for detection of early ictal activity. This study was undertaken to verify that both acute and spontaneous recurrent seizures in the systemic KA model have hippocampal and extrahippocampal onsets. Methods: Eight male Sprague Dawley rats with depth electrodes were continuously recorded during intraperitoneal injections of KA at a dose of 5mg/Kg every hour until status epilepticus (SE) was induced (ranging 3-7 hours). Another group of 4 rats were monitored chronically up to 2 weeks after emergence of spontaneous recurrent seizures. All acutely monitored rats (n=8) had at least one of their four depth electrodes in the CA3 region of the hippocampus, and 7 rats had an electrode in the contralateral hippocampus. The other electrodes were implanted in bilateral claustra (n=3); bilateral piriform cortices (n=2); bilateral corpus callosum (n=1); bilateral orbital cortices (n=1); and the contralateral deep cerebral white matter, ipsilateral orbital cortex, and contralateral frontal cortex (n=1). The 4 chronically monitored rats had electrodes in bilateral hippocampi and anterior piriform cortices. Seizures recorded with video-EEG were visually analyzed. Results: We recorded 58 seizures from 8 rats during KA injections. The seizure onset zone was extrahippocampal in 7 (12%), diffuse in 29 (50%), and hippocampal in 22 (38%). Of the 14 spontaneous seizures recorded from the 4 rats in the chronic study, none were solely extra-hippocampal, 8 (57%) were diffuse, and 6 (43%) were of hippocampal onset. Earliest ictal activity during acute seizures localized to the claustrum in 2 out of 11 seizures recorded from animals with claustral electrodes, 2 out of 8 seizures recorded from the forceps minor of the corpus callosum, 2 out of 4 from the orbital cortex, 1 out of 5 from the frontal cortex, and 22 out of 58 from the hippocampus. Earliest ictal activity during spontaneous recurrent seizures localized to the piriform cortex together with the hippocampus, and solely in the hippocampus. All seizures with extra-hippocampal onset propagated to the hippocampus with latencies ranging from four seconds to 50 seconds with an average of 14 seconds (n=7). No distinctive semiological manifestations correlated with the onset zones. Conclusions: KA-induced status epilepticus via systemic injections results in multifocal epileptogenesis. Although all seizures eventually involved the hippocampus, preceding and simultaneous ictal activity was detected in multiple locations suggesting that the model can produce multifocal and extra-temporal lobe seizures both during its acute and spontaneous phases. These findings are important to consider when using the KA model, among other purposes, to screen for new therapies, study pharmacoresistance, or investigate comorbidities of epilepsy. Funding: This study was made possible by the startup funds from the George Washington University for MZK.