Abstracts

Rationale: Animal models of epilepsy and seizures are used to understand the mechanisms underlying epileptogenesis in the different forms of epilepsy, develop therapies, and better treat comorbidities and drug resistant epilepsy. Their use in epilepsy research, however, is associated with considerable welfare cost to the animals involved. Such models represent an important area for application of the 3Rs (replacement, reduction and refinement of animal use); with the potential for refinement of seizure induction, maintenance and monitoring of animals to minimize any pain or distress and improve scientific outcomes.Methods: An expert working group to review the current use of rodent models of epilepsy and identify opportunities for refinement was convened by the NC3Rs, a scientific organisation established by the UK government (www.nc3rs.org.uk/epilepsy). The working group comprised neuroscientists, neurologists, epileptologists, neurosurgeons and veterinarians from academia and the pharmaceutical industry with experience covering a range of epilepsy research areas. It surveyed the international epilepsy community to identify which mammalian models are used in epilepsy research and to define best practice. In addition to the survey, a systematic review of the scientific literature was carried out to identify supporting evidence. The survey, literature review and expert opinion and practical experience of the members of the working group were used to define recommendations.Results: The working group has provided researchers, veterinarians and animal care staff with the tools to refine the use of rodent models of epilepsy and seizures. Recommendations include induction procedures, in vivo recordings, perioperative care, welfare assessment, humane endpoints, social housing, environmental enrichment and reporting of studies and data sharing. In addition, some model-specific adverse effects and refinements were identified for commonly used models. Areas where increased knowledge and technological development would facilitate refinement and best practice were identified and highlighted as priorities for further research.Conclusions: Opportunities for refinement of the use of rodent models of epilepsy and seizures were identified; implementation of the recommendations could help to improve the quality of animal studies in epilepsy research and maximize the use of animals.