CHARACTERISING FACE VALIDITY OF SLEEP-DISTURBANCE IN THE INTRAHIPPOCAMPAL KAINIC ACID MODEL OF TEMPORAL LOBE EPILEPSY

Temporal Lobe Epilepsy (TLE) is commonly associated with cognitive and psychiatric comorbidities, and over 60% of patients report disrupted sleep. Although human studies suggest a bidirectional relationship between sleep and epilepsy, mechanistic insights are limited by anti-seizure medications and clinical constraints. Here, we assess the face validity of the intrahippocampal kainic acid (KA) mouse model by characterising sleep–wake patterns and the circadian timing of seizures and epileptiform activity across epileptogenesis.
We employed long-term, continuous telemetric electrocorticography for 40 days in KA-injected and control mice. This longitudinal approach captured the progression from status epilepticus (within 30 minutes of KA injection up to 24 hours) through the emergence of spontaneous recurrent seizures (within 2–5 days post injection), which increased over time, and then plateaued. Sleep macro- and microstructure were analysed using automated scoring and compared between groups. In addition, using multisite local field potential (LFP), the circadian rhythm of epileptiform activity in 48 hours of continuous recording was captured.
One week post-SE, epileptic animals displayed significant alterations in sleep structure, characterised by increased wakefulness during the light phase and a higher percentage of REM sleep during the light and dark phase. Notably, seizures occurred significantly more frequently at the beginning of the light phase, reflecting circadian modulation of seizure occurrence. A similar trend can be observed in high power discarges (HPDs) in the LFP recordings.
Compared to observations in patients with TLE, our findings demonstrate that the intrahippocampal KA model effectively replicates the sleep disturbances and circadian seizure distributions.
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