title: 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.
authors.affiliation: Aston Brain Centre, Aston University, School of Life and Health Sciences, Birmingham, United Kingdom.
authors.forename: Tamara
authors.initials: T
authors.lastname: Modebadze
authors.affiliation: Aston Brain Centre, Aston University, School of Life and Health Sciences, Birmingham, United Kingdom.
authors.forename: Nicola H
authors.initials: NH
authors.lastname: Morgan
authors.affiliation: School of Pharmacy, Hopkins Life Sciences Building, University of Reading, Whiteknights, Reading, Berkshire, United Kingdom.
authors.forename: Isabelle A A
authors.initials: IA
authors.lastname: Pérès
authors.affiliation: School of Pharmacy, Hopkins Life Sciences Building, University of Reading, Whiteknights, Reading, Berkshire, United Kingdom.
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Hadid
authors.affiliation: School of Pharmacy, Hopkins Life Sciences Building, University of Reading, Whiteknights, Reading, Berkshire, United Kingdom.
authors.forename: Naoki
authors.initials: N
authors.lastname: Amada
authors.affiliation: School of Pharmacy, Hopkins Life Sciences Building, University of Reading, Whiteknights, Reading, Berkshire, United Kingdom.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Hill
authors.affiliation: School of Pharmacy, Hopkins Life Sciences Building, University of Reading, Whiteknights, Reading, Berkshire, United Kingdom.
authors.forename: Claire
authors.initials: C
authors.lastname: Williams
authors.affiliation: Aston Brain Centre, Aston University, School of Life and Health Sciences, Birmingham, United Kingdom.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Stanford
authors.affiliation: Medical Toxicology Centre, Newcastle University, Wolfson Building, Claremont Place, Newcastle upon Tyne, United Kingdom.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Morris
authors.affiliation: Department of Pharmacology, University of Bath, Claverton Down, Bath, United Kingdom.
authors.forename: Roland S G
authors.initials: RS
authors.lastname: Jones
authors.affiliation: School of Pharmacy, Hopkins Life Sciences Building, University of Reading, Whiteknights, Reading, Berkshire, United Kingdom.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Whalley
authors.affiliation: Aston Brain Centre, Aston University, School of Life and Health Sciences, Birmingham, United Kingdom.
authors.forename: Gavin L
authors.initials: GL
authors.lastname: Woodhall
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D008297:Male; D009017:Morbidity; D051381:Rats; D017208:Rats, Wistar; D012008:Recurrence; D013226:Status Epilepticus / Q000453:epidemiology* / Q000401:mortality / Q000473:pathology