A low mortality, high morbidity Reduced Intensity Status Epilepticus (RISE) model of epilepsy and epileptogenesis in the rat

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 DOI: https://doi.org/10.1371/journal.pone.0147265
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences > Clinical and Systems Neuroscience
College of Health & Life Sciences
College of Health & Life Sciences > Aston Institute of Health & Neurodevelopment (AIHN)
Additional Information: © 2016 Modebadze et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Uncontrolled Keywords: Animals,Behavior, Animal,Disease Models, Animal,Disease Progression,Humans,Male,Morbidity,Rats,Rats, Wistar,Recurrence,Status Epilepticus,Agricultural and Biological Sciences(all),Biochemistry, Genetics and Molecular Biology(all),Medicine(all)
Publication ISSN: 1932-6203
Last Modified: 16 May 2024 07:10
Date Deposited: 10 Mar 2016 09:35
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://journals ... al.pone.0147265 (Publisher URL)
PURE Output Type: Article
Published Date: 2016-02-24
Accepted Date: 2016-02-02
Submitted Date: 2014-01-13
Authors: Modebadze, Tamara
Morgan, Nicola H.
Pérès, Isabelle A.A.
Hadid, Rebecca D.
Amada, Naoki
Hill, Charlotte
Williams, Claire
Stanford, Ian M. (ORCID Profile 0000-0002-5677-8538)
Morris, Christopher M.
Jones, Roland S.G.
Whalley, Benjamin J.
Woodhall, Gavin L. (ORCID Profile 0000-0003-1281-9008)

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