Clustering of Spontaneous Recurrent Seizures in a Mouse Model of Extended Hippocampal Kindling

Abstract

Acute repetitive seizures or seizure clusters are common in epileptic patients. Seizure clusters are associated with a high risk of developing status epilepticus and increased morbidity and mortality. Seizure clusters are also recognizable in spontaneous recurrent seizures (SRS) that occur in animal models of epilepsy. The electrical kindling of a limbic structure is a commonly used model of temporal lobe epilepsy. Although classic kindling over the course of a few weeks does not generally induce SRS, extended kindling over the course of a few months can induce SRS in several animal species. SRS in kindled cats often occur in clusters, but the existence of seizure clusters in rodent models of extended kindling remains to be demonstrated. We explored the existence of seizure clusters in mice following extended hippocampal kindling. Adult male mice (C57BL/6) experienced twice daily hippocampal stimulations and underwent continuous 24-hour electroencephalogram (EEG)-video monitoring after ≥80 stimulations. SRS events were recognized by EEG discharges and associated motor seizures. Seizure clusters, defined as ≥4 seizures per cluster and intra-cluster inter-seizure intervals ≤ 120 min, were observed in 19 of the 20 kindled mice. Individual mice showed variable seizure clusters in terms of cluster incidence and circadian-like expression patterns. For clusters consisting of 4–7 seizures and intra-seizure intervals ≤ 20 min, no consistent changes in inter-seizure intervals, EEG discharge duration, or motor seizure severity scores were observed approaching cluster termination. These results suggested that seizure clustering represents a prominent feature of SRS in hippocampal kindled mice. We speculate that, despite experimental limitations and confounding factors, systemic homeostatic mechanisms that have yet to be explored may play an important role in governing the occurrence and termination of seizure clusters.

Convulsive behaviors of spontaneous recurrent seizures in a mouse model of extended hippocampal kindling

“…Our lab has established a protocol of extended hippocampal kindling in mice. Previous works of our lab examined responses of SRS to some of the clinically used antiepileptic drugs (Song et al, 2018), clustering expression of SRS (Liu and Zhang, 2021), spatial memory impairment (Liu et al, 2019), and regional expression and waveforms of spontaneous EEG discharges in the mouse model of extended hippocampal kindling. The aim of the present study was to continue characterize SRS in kindled mice, with a particular focus on motor seizure severity and seizurepreceding behaviors.…”