Epilepsy and seizures

Authors:

Katie Lidster

John G. Jefferys

Ingmar Blümcke

Vincenzo Crunelli

Paul Flecknell

Bruno G. Frenguelli

William P. Gray

Rafal Kaminski

Asla Pitkänen

Ian Ragan

Mala Shah

Michele Simonato

Andrew Trevelyan

Holger Volk

Matthew Walker

Neil Yates

Mark J. Prescott

Publication:

Journal of Neuroscience Methods 260, 2-25

Publish Date:

15 September 2016

Background

Rodent models are widely used in epilepsy and seizure research to understand pathophysiology, identify biomarkers, and develop new treatments for epilepsy and its associated conditions. Therefore, this field of research presents an important area for applying the 3Rs (Replacement, Reduction, Refinement).

Summary

This comprehensive report offers information and recommendations to alleviate pain, suffering, and distress in rodent models of epilepsy and seizures, thereby enhancing animal welfare and the quality of studies. It provides practical advice on model selection, induction procedures, in vivo recordings, perioperative care, welfare assessment, humane endpoints, social housing, environmental enrichment, and best practices for reporting and data sharing. Additionally, the report addresses specific welfare considerations for certain models and highlights areas needing further research.

Key Actions

Choose the most appropriate model taking into account the type of epilepsy being modelled and the specific scientific question, as well as the need to minimise animal numbers and their suffering.
Refine the procedure, including induction, in vivo recordings, and perioperative care, and tailor these to the scientific objectives, while minimising harms and mortality.
Implement appropriate welfare assessments and adjust them to the specific model used.
Tailor humane endpoints for each experiment, taking into consideration the current legal framework, scientific, justifiable and unpredictable endpoints, and the results of welfare assessments.

Read the full Epilepsy and seizures report

Download report

Further questions

First, choose an appropriate strain for seizure susceptibility and responses to antiepileptic drugs. Age is also crucial because brain function alters throughout development, affecting sensitivity to chemoconvulsants, seizure latency and intensity, mortality and pharmacological responses. Select the right breeder, as there can be variations between suppliers regarding anxiety, seizure susceptibility, epileptogenesis and even mortality rates. Also, consider sex due to differences in epilepsy susceptibility, the influence of sex hormones on seizures, and sex differences in brain pathways and drug responses. Both sexes should be used unless one sex is needed for specific study objectives.
The main animal welfare knowledge gaps in epilepsy studies include (but are not limited to):
- A deeper understanding of animals' subjective experiences during, between, and after seizures
- The need for technological advancements in electrophysiological devices, including improved biocompatibility, reliability, miniaturisation, and battery life for long-term telemetry
- Increased knowledge about how anaesthetic agents and common analgesics interact with seizure susceptibility and intensity
- Improved understanding of the generalisability and relevance of seizure scoring systems across different animal models and age groups

Authors

Katie Lidster - National Centre for Replacement, Refinement and Reduction of Animals in Research

John G. Jefferys - University of Oxford

Ingmar Blümcke - University of Erlangen

Vincenzo Crunelli - Cardiff University

Paul Flecknell - Newcastle University

Bruno G. Frenguelli - University of Warwick

William P. Gray - Cardiff University

Rafal Kaminski - UCB Pharma

Asla Pitkänen - University of Eastern Finland

Ian Ragan - NC3Rs Board

Mala Shah - University College London

Michele Simonato - University of Ferrara

Andrew Trevelyan - Newcastle University

Holger Volk - The Royal Veterinary College

Matthew Walker - University College London

Neil Yates - University of Nottingham

Mark J. Prescott - National Centre for Replacement, Refinement and Reduction of Animals in Research