Kindling Models of Epileptogenesis for Developing Disease-Modifying Drugs for Epilepsy.

Publisher: John Wiley & Sons Country of Publication: United States NLM ID: 101773894 Publication Model: Print Cited Medium: Internet ISSN: 2691-1299 (Electronic) Linking ISSN: 26911299 NLM ISO Abbreviation: Curr Protoc Subsets: MEDLINE

Original Publication: Hoboken, NJ : John Wiley & Sons, [2021]-

Kindling, Neurologic*/drug effects ; Epilepsy*/drug therapy ; Epilepsy*/physiopathology ; Epilepsy*/chemically induced ; Disease Models, Animal* ; Anticonvulsants*/pharmacology ; Anticonvulsants*/therapeutic use; Animals ; Mice ; Drug Development/methods ; Pentylenetetrazole/pharmacology

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 kindling Basic Protocol 2: Amygdala kindling Basic Protocol 3: Rapid hippocampal kindling Basic Protocol 4: Chemical kindling.
(© 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC.)

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U01 NS117209 United States NS NINDS NIH HHS; U01 NS117278 United States NS NINDS NIH HHS

Keywords: amygdala kindling; antiseizure medications; chemical kindling; epileptogenesis; hippocampal kindling; pentylenetetrazol; rapid hippocampal kindling

0 (Anticonvulsants)
WM5Z385K7T (Pentylenetetrazole)

Date Created: 20241022 Date Completed: 20241022 Latest Revision: 20241025

20241025

PMC11498896

10.1002/cpz1.70020

39436626