Experimental models of epilepsy: A comprehensive review of mechanisms, translational relevance, and future directions

Epilepsy is a chronic neurological disorder characterized by recurrent seizures, affecting millions worldwide. Experimental models play a crucial role in understanding the pathophysiology of seizures and in developing novel antiepileptic therapies. This review summarizes the major experimental models of epilepsy, including chemically induced, electrically induced, and genetic approaches. The strengths, limitations, and translational relevance of each model are discussed with particular emphasis on their applicability to human epilepsy subtypes, such as generalized tonic-clonic and temporal lobe epilepsy. Advances in neuroimaging, omics technologies, and artificial intelligence-based analytics are highlighted for their potential to enhance model accuracy and predictive validity. Ethical considerations, including the principles of replacement, reduction, and refinement, are also emphasized. By integrating classical models with emerging technologies, this review provides a comprehensive framework to guide future research aimed at improving therapeutic strategies and bridging the gap between pre-clinical and clinical epilepsy research.