Epilepsy

Authors:

Tamara Modebadze

Nicola H. Morgan

Isabelle A. A. Pérès

Rebecca D. Hadid

Naoki Amada

Charlotte Hill

Claire Williams

Ian M. Stanford

Christopher M. Morris

Roland S G. Jones

Benjamin J. Whalley

Gavin L. Woodhall

Publication:

PLoS ONE 11(2), e0147265 doi:10.1371/journal.pone.0147265

Publish Date:

24 February 2016

Background

For decades, animal models have been used to study epilepsy. The procedures in these models often lead to high mortality, which presents clear concerns for animal welfare. The implementation of the 3Rs (Replacement, Refinement, Reduction) aims not only to decrease animal usage and suffering but also to enhance the scientific validity of the models, for instance, by better mirroring the natural progression of a disease.

Summary

Animal models for acquired epilepsies are used to understand how the disorder is acquired, develops, and becomes established. Generally, after a systemic or local injury, susceptible brain areas undergo changes that eventually lead to spontaneous, recurring seizures. Many existing models employ a period of severe seizure activity, known as status epilepticus, which can result in significant mortality or extensive brain damage. In this paper, the authors propose a model that reduces mortality to 1% whilst retaining the features and development of spontaneous seizures.

Key Actions

Consider using models with reduced mortality.
Implement refinements to minimise global neuronal damage.
Control acute seizure severity and duration (e.g. administering xylazine during the acute seizure phase).
Implement non-invasive behavioural monitoring systems, such as the post-seizure behavioural battery.

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Further questions

RISE is an optimised chronic epilepsy model, using rats, that has reduced the mortality rate to ~1% (from typical rates of 40-80%), while still retaining high epileptogenicity and the development of spontaneous seizures. It reduces the severity of acute seizures, prevents convulsive elements, and ensures rapid termination of the acute seizure phase. This reduces stressful effects and complications.
The RISE model is said to be readily repeatable across sites and therefore, easy to adopt. It has been used to develop a new treatment, Epidyolex (Epidiolex outside Europe), which significantly reduces seizures and is used to treat epilepsy patients with resistant syndromes.

Authors

Tamara Modebadze - Aston University

Nicola H. Morgan - Aston University

Isabelle A. A. Pérès - University of Reading

Rebecca D. Hadid - University of Reading

Naoki Amada - University of Reading

Charlotte Hill - University of Reading

Claire Williams - University of Reading

Ian M. Stanford - Aston University

Christopher M. Morris - Newcastle University

Roland S. G. Jones - University of Bath

Benjamin J. Whalley - University of Reading

Gavin L. Woodhall - Aston University