Experimental epilepsy models for mechanistic investigation and translational research
Epilepsy is not merely a chronic neurological disorder characterized by recurrent, spontaneous seizures at the clinical level; rather, it represents a complex pathophysiological condition involving profound structural, functional, and molecular reorganization within neuronal networks. The marked heterogeneity of epilepsy arises from the multilayered interplay of genetic susceptibility, acquired brain insults such as trauma, ischemia, or infection, developmental abnormalities, and environmental factors. This multifactorial etiology poses substantial challenges for clinical management and limits the effectiveness of current therapeutic approaches, which are largely restricted to symptomatic seizure suppression. Experimental epilepsy models constitute indispensable tools for addressing these unmet clinical and scientific needs. Chemical, electrical, genetic, and acquired models enable systematic investigation of epilepsy across multiple biological scales, ranging from alterations in neuronal excitability and synaptic plasticity to neuroinflammatory processes and network-level synchronization disturbances. Beyond providing mechanistic insight, these models serve as essential platforms for preclinical evaluation of novel pharmacological agents and neuromodulation-based therapeutic strategies. The review encompasses a broad experimental spectrum, including chemoconvulsant models such as pentylenetetrazol, pilocarpine, and kainic acid; electrical stimulation paradigms; genetic and developmental models; and acquired epilepsy models. In addition, in vitro and ex vivo systems, outcome measures, and model optimization strategies for drug screening and therapeutic development are discussed. By highlighting the limitations of single-model approaches and emphasizing complementary experimental strategies, this review aims to advance a comprehensive understanding of epilepsy pathophysiology and support the development of more effective, mechanism-based therapies.