Optimised induction of on-demand focal hippocampal and neocortical seizures by electrical stimulation
File(s)Accepted Manuscript_Hannan_14-08-20.pdf (1.29 MB)
Accepted version
Author(s)
Type
Journal Article
Abstract
BACKGROUND: Epilepsy is a common neurological disorder affecting over 60 million people globally, approximately a third of whom are refractory to pharmacotherapy. Surgical resection of the epileptogenic zone is frequently unsuitable or ineffective, particularly for individuals with focal neocortical or mesial temporal lobe epilepsy. Therefore, there is a need to develop animal models for elucidating the mechanisms of focal epilepsies and evaluating novel treatment strategies. NEW METHOD: We present two adapted in vivo seizure models, the neocortical and hippocampal epileptic afterdischarge models, that enable stereotyped seizures to be induced on demand by electrical stimulation in anaesthetised, neurologically intact rats. The stimulation parameters and anaesthetic were optimised to generate electrographically reproducible, self-sustaining seizures with a well-defined focal origin. RESULTS: Neocortical or hippocampal seizures were consistently generated under fentanyl-isoflurane anaesthesia by stimulating the sensorimotor cortex or perforant path, respectively, with 100 Hz trains of biphasic square-wave pulses. The induced seizures were suppressed by propofol, an established antiseizure anaesthetic, thus validating the clinical responsiveness of the developed models. COMPARISON WITH EXISTING METHODS: The high degree of reproducibility in seizure presentation, predictable seizure induction and ability to operate in anaesthetised animals renders these models overall less laborious and more cost-effective than most conventionally used seizure models. CONCLUSIONS: The proposed models provide an efficient method for the high-throughput screening of novel antiseizure therapies, including closed-loop stimulation paradigms, and are well-suited to in vivo investigations that require tight regulation of seizure timing under anaesthetised conditions, particularly neuroimaging studies aimed at understanding the development of epileptogenic networks.
Date Issued
2020-12-01
Date Acceptance
2020-08-12
Citation
Journal of Neuroscience Methods, 2020, 346, pp.108911-108911
ISSN
0165-0270
Publisher
Elsevier
Start Page
108911
End Page
108911
Journal / Book Title
Journal of Neuroscience Methods
Volume
346
Copyright Statement
© 2020 Elsevier B.V. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/32805315
PII: S0165-0270(20)30334-4
Grant Number
RDB04
Subjects
anaesthetic
animal model
electrical stimulation
epilepsy
hippocampus
neocortex
rat
seizure
Publication Status
Published
Coverage Spatial
Netherlands
Article Number
ARTN 108911
Date Publish Online
2020-08-14