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

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

Research output: Contribution to journalArticle

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.
LanguageEnglish
Article numbere0147265
Number of pages19
JournalPLoS ONE
Volume11
Issue number2
DOIs
Publication statusPublished - 24 Feb 2016

Fingerprint

epilepsy
Status Epilepticus
morbidity
seizures
Rats
Epilepsy
Seizures
Morbidity
Mortality
rats
Animals
animal use replacement
animal use refinement
animal use reduction
Pilocarpine
Brain
pilocarpine
brain
Lithium
lithium

Bibliographical note

© 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.

Keywords

  • Animals
  • Behavior, Animal
  • Disease Models, Animal
  • Disease Progression
  • Humans
  • Male
  • Morbidity
  • Rats
  • Rats, Wistar
  • Recurrence
  • Status Epilepticus

Cite this

Modebadze, Tamara ; Morgan, Nicola H. ; Pérès, Isabelle A.A. ; Hadid, Rebecca D. ; Amada, Naoki ; Hill, Charlotte ; Williams, Claire ; Stanford, Ian M. ; Morris, Christopher M. ; Jones, Roland S.G. ; Whalley, Benjamin J. ; Woodhall, Gavin L. / A low mortality, high morbidity Reduced Intensity Status Epilepticus (RISE) model of epilepsy and epileptogenesis in the rat. In: PLoS ONE. 2016 ; Vol. 11, No. 2.
@article{4d73881a277f48bba101a5487ffce57e,
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.",
keywords = "Animals, Behavior, Animal, Disease Models, Animal, Disease Progression, Humans, Male, Morbidity, Rats, Rats, Wistar, Recurrence, Status Epilepticus",
author = "Tamara Modebadze and Morgan, {Nicola H.} and P{\'e}r{\`e}s, {Isabelle A.A.} and Hadid, {Rebecca D.} and Naoki Amada and Charlotte Hill and Claire Williams and Stanford, {Ian M.} and Morris, {Christopher M.} and Jones, {Roland S.G.} and Whalley, {Benjamin J.} and Woodhall, {Gavin L.}",
note = "{\circledC} 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.",
year = "2016",
month = "2",
day = "24",
doi = "10.1371/journal.pone.0147265",
language = "English",
volume = "11",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

A low mortality, high morbidity Reduced Intensity Status Epilepticus (RISE) model of epilepsy and epileptogenesis in the rat. / Modebadze, Tamara; Morgan, Nicola H.; Pérès, Isabelle A.A.; Hadid, Rebecca D.; Amada, Naoki; Hill, Charlotte; Williams, Claire; Stanford, Ian M.; Morris, Christopher M.; Jones, Roland S.G.; Whalley, Benjamin J.; Woodhall, Gavin L.

In: PLoS ONE, Vol. 11, No. 2, e0147265, 24.02.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A low mortality, high morbidity Reduced Intensity Status Epilepticus (RISE) model of epilepsy and epileptogenesis in the rat

AU - Modebadze, Tamara

AU - Morgan, Nicola H.

AU - Pérès, Isabelle A.A.

AU - Hadid, Rebecca D.

AU - Amada, Naoki

AU - Hill, Charlotte

AU - Williams, Claire

AU - Stanford, Ian M.

AU - Morris, Christopher M.

AU - Jones, Roland S.G.

AU - Whalley, Benjamin J.

AU - Woodhall, Gavin L.

N1 - © 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.

PY - 2016/2/24

Y1 - 2016/2/24

N2 - 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.

AB - 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.

KW - Animals

KW - Behavior, Animal

KW - Disease Models, Animal

KW - Disease Progression

KW - Humans

KW - Male

KW - Morbidity

KW - Rats

KW - Rats, Wistar

KW - Recurrence

KW - Status Epilepticus

UR - http://www.scopus.com/inward/record.url?scp=84962576987&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0147265

DO - 10.1371/journal.pone.0147265

M3 - Article

VL - 11

JO - PLoS ONE

T2 - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 2

M1 - e0147265

ER -