Rodent models of epilepsy
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.
Read a summary of the recommendations: Opportunities for improving animal welfare in rodent models of epilepsy and seizures.
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.
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
|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|
- 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)
- Poster presented at American Epilepsy Society, December 2015 and FENS Forum of Neurosceince, July 2016: Opportunities for improving animal welfare in rodent models of epilepsy and seizures (PDF, 4 MB)
- Opportunities for improving animal welfare in rodent models of epilepsy and seizure (PDF, 490 KB). Published: December 2015