Amygdala Kindling Resistance in Rats with Genetic Absence Epilepsy: Role of Sex Differences

Epilepsy is a chronic neurological disorder characterized by spontaneous and recurrent seizures.It remains a significant global health issue, affecting approximately 50 million people worldwide. 1Understanding the mechanisms underlying epilepsy development and progression, known as epileptogenesis, is critical for developing more effective treatments. 2 One widely used experimental model to study epileptogenesis and seizure dynamics is the kindling model. 3In this model, repeated sub-treshold electrical stimulation of a specific brain region, often the amygdala, leads to the gradual development of seizures.Over time, this results in the generation of permanent changes in brain excitability, ultimately causing spontaneous seizures. 4,5The Racine scale, which ranges from stage 1 (mild facial clonus) to stage 5 (generalized tonic-clonic seizures), is commonly employed to classify seizure severity in kindling studies. 6The kindling model has been extensively studied in various rodent strains, each offering distinct insights into seizure susceptibility, progression, and resistance. 7Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is a well-established animal model for absence epilepsy, characterized by spontaneous spike-and-wave discharges (SWDs) seen on the electroencephalogram (EEG), which are also observed in human absence epilepsy. 8GAERS have traditionally been considered resistant to convulsive seizures, 5,9,10 making them an interesting model to study epileptogenesis. 11n contrast, Wistar rats, commonly used as a control group, are susceptible to kindling, which produces convulsive seizures. 7,12,13The