Kindling Models of Epileptogenesis for Developing Disease‐Modifying Drugs for Epilepsy

Abstract

Kindling models are widely used animal models to study the pathobiology of epilepsy and epileptogenesis. These models exhibit distinctive features whereby sub‐threshold stimuli instigate the initial induction of brief focal seizures. Over time, the severity and duration of these seizures progressively increase, leading to a fully epileptic state, which is marked by consistent development of generalized tonic‐clonic seizures. Kindling involves focal stimulation via implanted depth electrodes or repeated administration of chemoconvulsants such as pentylenetetrazol. Comparative analysis of preclinical and clinical findings has confirmed a high predictive validity of fully kindled animals for testing novel antiseizure medications. Thus, kindling models remain an essential component of anticonvulsant drug development programs. This article provides a comprehensive guide to working protocols, testing of therapeutic drugs, outcome parameters, troubleshooting, and data analysis for various electrical and chemical kindling epileptogenesis models for new therapeutic development and optimization. The use of pharmacological agents or genetically modified mice in kindling experiments is valuable, offering insights into the impact of a specific target on various aspects of seizures, including thresholds, initiation, spread, termination, and the generation of a hyperexcitable network. These kindling epileptogenesis paradigms are helpful in identifying mechanisms and disease‐modifying interventions for epilepsy. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC.Basic Protocol 1: Hippocampal kindlingBasic Protocol 2: Amygdala kindlingBasic Protocol 3: Rapid hippocampal kindlingBasic Protocol 4: Chemical kindling