Acute and spontaneous seizure onset zones in the intraperitoneal kainic acid model

- Kainate-induced seizures can have hippocampal, extrahippocampal, or diffuse onset.
- Differing onset patterns do not correlate with any semiological differences.
- More spontaneously recurring seizures had diffuse onsets than acute seizures.
- All seizures in the kainate model eventually involve the hippocampi.

ObjectiveHippocampal monitoring is often used in the intraperitoneal kainic acid (KA) seizure model for detection and quantification of early ictal activity. Here, we investigated extra-hippocampal seizure onset zones (SOZs) in this model.MethodsEight male Sprague Dawley rats implanted with depth electrodes were continuously recorded during intraperitoneal KA injections until status epilepticus (SE) was induced. Another group of four rats was monitored chronically up to two weeks after emergence of spontaneous recurrent seizures. All rats had hippocampal electrodes. Other sampled brain regions included, among others, the claustrum, piriform cortex, and orbital cortex. Seizures recorded with video-EEG were visually analyzed.ResultsIn the 58 seizures recorded during KA injections, the SOZ was extrahippocampal in 7 (12%), diffuse in 29 (50%), and hippocampal in 22 (38%). Of the 14 spontaneous seizures recorded, none were solely extrahippocampal, 10 (71%) were diffuse, and 4 (29%) were of hippocampal onset. All extra-hippocampal seizures propagated to the hippocampus within 4 to 50 s (mean = 14, n = 7). No distinctive semiological manifestations correlated with the SOZs.SignificanceWe conclude that seizures can have multifocal SOZs in the KA model. This finding is important to consider when using this model, among other purposes, to screen for new therapies, study pharmacoresistance, or investigate comorbidities of epilepsy.