TitleImmediate Epileptogenesis after Kainate-Induced Status Epilepticus in C57BL/6J Mice: Evidence from Long Term Continuous Video-EEG Telemetry.
Publication TypeJournal Article
Year of Publication2015
AuthorsPuttachary, S, Sharma, S, Tse, K, Beamer, E, Sexton, A, Crutison, J, Thippeswamy, T
JournalPLoS One
Date Published2015
KeywordsAnimals, Anticonvulsants, Diazepam, Disease Models, Animal, Dose-Response Relationship, Drug, Electroencephalography, Injections, Intraperitoneal, Kainic Acid, Male, Mice, Inbred C57BL, Monitoring, Physiologic, Severity of Illness Index, Status Epilepticus, Telemetry, Time Factors, Video Recording

The C57BL/6J mouse as a model of seizure/epilepsy is challenging due to high mortality and huge variability in response to kainate. We have recently demonstrated that repeated administration of a low dose of kainate by intraperitoneal route can induce severe status epilepticus (SE) with 94% survival rate. In the present study, based on continuous video-EEG recording for 4-18 weeks from epidurally implanted electrodes on the cortex, we demonstrate that this method also induces immediate epileptogenesis (<1-5 days post-SE). This finding was based on identification of two types of spontaneous recurrent seizures; behavioral convulsive seizures (CS) and electrographic nonconvulsive seizures (NCS). The identification of the spontaneous CS, stage 3-5 types, was based on the behaviors (video) that were associated with the EEG characteristics (stage 3-5 epileptiform spikes), the power spectrum, and the activity counts. The electrographic NCS identification was based on the stage 1-2 epileptiform spike clusters on the EEG and their associated power spectrum. Severe SE induced immediate epileptogenesis in all the mice. The maximum numbers of spontaneous CS were observed during the first 4-6 weeks of the SE and they decreased thereafter. Mild SE also induced immediate epileptogenesis in some mice but the CS were less frequent. In both the severe and the mild SE groups, the spontaneous electrographic NCS persisted throughout the 18 weeks observation period, and therefore this could serve as a chronic model for complex seizures. However, unlike rat kainate models, the C57BL/6J mouse kainate model is a unique regressive CS model of epilepsy. Further studies are required to understand the mechanism of recovery from spontaneous CS in this model, which could reveal novel therapeutic targets for epilepsy.

Alternate JournalPLoS ONE
PubMed ID26161754
PubMed Central IDPMC4498886
Grant List / / Biotechnology and Biological Sciences Research Council / United Kingdom