Animal models of epilepsy represent an important area for application of the 3Rs. An expert working group led by the NC3Rs identified opportunities for refining rodent models of epilepsy and seizures. The findings of the working group are available in a report published in Journal of Neuroscience Methods in 2015, which provides practical recommendations for researchers, veterinarians and animal care staff.
A large diversity of acute and chronic mammalian models, mostly involving mice and rats, are used to research clinical epilepsies. Some of the procedures used to induce, maintain and monitor seizures can be distressing for the animals and in the UK are classified as causing moderate or severe suffering.
The working group surveyed the international epilepsy research community to identify which mammalian models are used, their limitations, and how adverse effects are minimised. The survey results, in combination with a review of the scientific literature and the expert opinion and practical experience of the group members, were used to define opportunities for refinement of mammalian models of epilepsy. The full report provides further information and practical approaches in the following areas:
Choice of animal model
Induction procedures
In vivo recordings
Perioperative care
Welfare assessment
Humane endpoints
Social housing
Environmental enrichment
Reporting and data sharing.
Implementation of the recommendations could help to improve the quality of animal studies in epilepsy research and maximise the use of the animals.
Our initiative complements the Translational Research Task Force led by the International League Against Epilepsy (ILAE) and American Epilepsy Society (AES) to optimise and accelerate preclinical epilepsy therapy discovery. Both ILAE and AES assisted with data collection.
Research funding
Areas for further research to facilitate refinement and best practice in the use of animal models of epilepsy and seizures were highlighted in the report. We have invested over £1 million in research to develop non-animal models of epilepsy, including the use of social amoebae, and to refine existing rodent models.
Working group membership
Members
Institution
Dr Ian Ragan (Chair)
NC3Rs Board
Professor Ingmar Blümcke
University Hospital Erlangen
Professor Vincenzo Crunelli
Cardiff University
Professor Paul Flecknell
Newcastle University
Professor Bruno Frenguelli
University of Warwick
Professor Liam Gray
Cardiff University
Professor John Jefferys
University of Oxford
Dr Rafal Kaminski
UCB Pharma
Dr Katie Lidster
NC3Rs
Professor Asla Pitkänen
University of Eastern Finland
Dr Mark Prescott
NC3Rs
Dr Mala Shah
University College London
Professor Michele Simonato
University of Ferrara
Dr Andrew Trevelyan
Newcastle University
Dr Holger Volk
Royal Veterinary College
Professor Matthew Walker
University College London
Mr Neil Yates
University of Nottingham
Publications
Lidster K, Jefferys JG, Blümcke I et al. (2015). Opportunities for improving animal welfare in rodent models of epilepsy and seizures. Journal of Neuroscience Methods 260: 2-25. doi: 10.1016/j.jneumeth.2015.09.007
Jeffreys JG (2017) Good welfare practices in modelling seizures and epilepsy. In: Models of Sezures and Epilepsy, 2nd. edition (Pitkänen A. Buckmasyter PS, Galanopoulou AS, Moshé SL, Eds.), pp. 39-46. https://doi.org/10.1016/B978-0-12-804066-9.00004-3
Jefferys JGR & Prescott MJ (2022) Refinement of rodent models of seizures and epilepsy. In: Engel J Jr., Moshe SL (Eds.) Epilepsy: A Comprehensive Textbook, 3rd Edn. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. (in press)