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A Low Mortality, High Morbidity Reduced Intensity Status Epilepticus (RISE) Model of Epilepsy and Epileptogenesis in the Rat

Lookup NU author(s): Dr Tamara Modebadze, Dr Christopher Morris

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Animal models of acquired epilepsies aim to provide researchers with tools for use in understanding the processes underlying the acquisition, development and establishment of the disorder. Typically, following a systemic or local insult, vulnerable brain regions undergo a process leading to the development, over time, of spontaneous recurrent seizures. Many such models make use of a period of intense seizure activity or status epilepticus, and this may be associated with high mortality and/or global damage to large areas of the brain. These undesirable elements have driven improvements in the design of chronic epilepsy models, for example the lithium-pilocarpine epileptogenesis model. Here, we present an optimised model of chronic epilepsy that reduces mortality to 1% whilst retaining features of high epileptogenicity and development of spontaneous seizures. Using local field potential recordings from hippocampus in vitro as a probe, we show that the model does not result in significant loss of neuronal network function in area CA3 and, instead, subtle alterations in network dynamics appear during a process of epileptogenesis, which eventually leads to a chronic seizure state. The model's features of very low mortality and high morbidity in the absence of global neuronal damage offer the chance to explore the processes underlying epileptogenesis in detail, in a population of animals not defined by their resistance to seizures, whilst acknowledging and being driven by the 3Rs (Replacement, Refinement and Reduction of animal use in scientific procedures) principles.


Publication metadata

Author(s): Modebadze T, Morgan NH, Peres IAA, Hadid RD, Amada N, Hill C, Williams C, Stanford IM, Morris CM, Jones RSG, Whalley BJ, Woodhall GL

Publication type: Article

Publication status: Published

Journal: PLoS ONE

Year: 2016

Volume: 11

Issue: 2

Online publication date: 24/02/2016

Acceptance date: 02/01/2016

Date deposited: 12/05/2016

ISSN (electronic): 1932-6203

Publisher: Public Library of Science

URL: http://dx.doi.org/10.1371/journal.pone.0147265

DOI: 10.1371/journal.pone.0147265


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