Decoding Epileptic Seizures: Exploring In Vitro Approaches to Unravel Pathophysiology and Propel Future Therapeutic Breakthroughs

Epilepsy is a chronic neurological disorder associated with various symptoms, contingent upon the specific brain region involved. Unpredictable seizures characterize epilepsy, significantly influencing the quality of the patient’s life. Globally, epilepsy affects 1% of the population, with 30% of individuals developing drug resistant epilepsy despite anti-epileptic pharmacological treatment. While several anticonvulsant drugs alleviate epilepsy symptoms, there is currently no effective medication to cure this neurological disorder. Therefore, overcoming the challenges of predicting and controlling drug-resistant seizures requires further knowledge of the pathophysiology of epilepsy at the molecular and cellular levels. In this review, we delve into in vitro experiments that prove valuable in elucidating the mechanisms of drug-resistant epilepsy, as well as in the development and testing of novel therapeutic approaches prior to extensive animal-based trials. Specifically, our focus is on the utility of multi-electrode array (MEA) recording as an in vitro technique for evaluating aberrant electrical activity within neural networks. Real-time MEA recording from neuronal cultures facilitates monitoring of neurotoxicity, dose response, and the efficacy of newly-designed drugs. Additionally, when coupled with emerging techniques such as optogenetics, MEA enables the creation of closed-loop systems for seizure prediction and modulation. These integrated systems contribute to both prospective therapy and the study of intracellular pathways in drug-resistant seizures, shedding light on their impact on neuronal network activity.