Hippocampal AIM2 inflammasome regulate seizure and cognitive impairment in mice with temporal lobe epilepsy

Epilepsy is a chronic neurological disorder characterized by spontaneous recurrent seizures. Approximately 30% of patients are resistant to current antiepileptic drugs, highlighting the need for further investigation into the underlying mechanisms of epilepsy. Studies have shown significant neuroinflammatory responses in specific brain regions of human epilepsy foci and in animal models. AIM2 (Absent in Melanoma 2) is an important neuroinflammatory factor involved in regulating brain function, but its precise role in epilepsy remains unclear. This study aimed to explore the role of AIM2 in hippocampal seizure development and cognitive impairment in temporal lobe epilepsy (TLE) models. In the TLE model induced by kainic acid (KA), the level of AIM2 in the hippocampus was increased. Subsequently, adenovirus (AAV)-mediated AIM2 knockdown was injected into the bilateral hippocampus of the TLE models. The results showed that knocking down AIM2 reduced the frequency and duration of epileptic seizures, downregulated the expression of the AIM2 inflammasome, Caspase-1, and IL-1β, alleviated the inflammatory response, and improved cognitive function. This study demonstrated that the AIM2 inflammasome plays a crucial role in regulating seizures and cognitive impairments in TLE, providing a potential new target for therapeutic strategies in the clinical management of epilepsy. • First study to identify the critical role of AIM2 inflammasome in KA-induced TLE models. • Inhibition of AIM2 reduces seizure frequency and improves cognitive function. • AIM2 modulates neuroinflammation through the Caspase-1/IL-1β signaling pathway. • AIM2 inhibition shows potential as a new therapeutic target for epilepsy treatment. • Future studies should explore AIM2 inhibition using small molecules or RNA-based therapies.