SEX DEPENDENT CHARACTERISATION OF THE SYSTEMIC KAINIC ACID MODEL OF TEMPORAL LOBE EPILEPSY IN MICE

Epilepsy is one of the most prevalent neurological disorders and is characterised by spontaneous recurrent seizures arising from disrupted excitation–inhibition balance. Temporal lobe epilepsy (TLE), the most common drug-resistant form, often develops after brain insults that initiate sustained molecular reprogramming, neuroinflammation, neuronal loss, and synaptic reorganisation. Although biological sex influences seizure susceptibility and disease progression, sex-specific phenotyping remains limited in preclinical epilepsy research.
Long non-coding RNAs (lncRNAs) regulate transcription, chromatin architecture, and neuronal excitability. Several lncRNAs are dysregulated following status epilepticus, including the imprinted lncRNA H19, but their relationship to sex-dependent epilepsy phenotypes remains unclear.
Here, we characterised the systemic kainic acid (KA) model of TLE in male and female mice at acute (1-week) and chronic (4-week) post-SE timepoints. Following systemic KA administration, acute seizure severity was scored, and animals were monitored longitudinally. Behavioural assessments were performed to evaluate anxiety-like and memory-related outcomes, and histopathological analyses quantified seizure-associated brain pathology. At both timepoints, hippocampal tissue was collected by hemisecting the brain, with one hemisphere processed for histopathology and the other snap-frozen for RNA extraction and qPCR analysis of lncRNAs, including H19 and IGF2.
Systemic KA induced sex-dependent differences in seizure severity, behavioural impairments, and neuropathological features. These findings reveal divergent male and female responses within this widely used TLE model and provide a framework for integrating molecular, behavioural, and histological endpoints. This work underscores the importance of incorporating sex as a biological variable in experimental epilepsy research.