A low mortality, high morbidity reduced intensity status epilepticus (RISE) model of epilepsy and epileptogenesis in the rat

Modebadze, T., Morgan, N. H., Peres, I. A. A., Hadid, R. D., Amada, N., Hill, C., Williams, C. ORCID: https://orcid.org/0000-0003-4452-671X, Stanford, I. M., Morris, C. M., Jones, R. S. G., Whalley, B. J. and Woodhall, G. L. (2016) A low mortality, high morbidity reduced intensity status epilepticus (RISE) model of epilepsy and epileptogenesis in the rat. PLoS ONE, 11 (2). e0147265. ISSN 1932-6203 doi: 10.1371/journal.pone.0147265

Abstract/Summary

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.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/57423
Identification Number/DOI	10.1371/journal.pone.0147265
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
Publisher	Public Library of Science
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