Rodent models of epilepsy

We have convened an expert working group to review current use of rodent models of epilepsy and identify opportunities for refinement. This work was instigated at the request of academics from the epilepsy research community.

Antiepileptic drugs are poorly effective in a third of the population and the search for new drugs is a primary goal in epilepsy research. The discovery of new antiepileptic drugs relies on the use of animal models of seizures or epilepsy.

A large diversity of acute and chronic mammalian models, mostly involving mice and rats, are used to research clinical epilepsies. Acute models are evoked by chemical stimulation (e.g. pilocarpine, tetanus toxin) or electrical stimulation (e.g. maximal electroshock seizure) triggering epileptic activity in the normal brain. Chronic models are evoked by an epileptogenic alteration either by genetic modification or insult (e.g. status epilepticus) leading to spontaneous seizures associated with pathogenic functional and structural changes in the brain. Some of these procedures can be distressing for the animal and in the UK are classified as causing moderate or severe suffering. There is the potential for refinement of seizure induction and maintenance of animals.

The working group has surveyed the international epilepsy research community to identify which mammalian models are used and to define best practice. In combination with a review of the scientific literature, the results of the survey will help to define opportunities for refinement and reduction in mammalian models of epilepsy.

Our initiative complements that of the International League Against Epilepsy and American Epilepsy Society to optimise and accelerate preclinical epilepsy therapy discovery, and both ILAE and AES have assisted with data collection.

Research funding

We have invested around £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

 

Opportunities for improving animal welfare in rodent models of epilepsy and seizure (PDF, 490 KB) 
Published: December 2015

 

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