Postictal behavioural impairments are due to a severe prolonged hypoperfusion/hypoxia event that is COX-2 dependent
- University of Calgary, Canada
Abstract
Seizures are often followed by sensory, cognitive or motor impairments during the postictal phase that show striking similarity to transient hypoxic/ischemic attacks. Here we show that seizures result in a severe hypoxic attack confined to the postictal period. We measured brain oxygenation in localized areas from freely-moving rodents and discovered a severe hypoxic event (pO2<10mmHg) after the termination of seizures. This event lasted over an hour, is mediated by hypoperfusion, generalizes to people with epilepsy, and is attenuated by inhibiting cyclooxygenase-2 or L-type calcium channels. Using inhibitors of these targets we separated the seizure from the resulting severe hypoxia and show that structure specific postictal memory and behavioral impairments are the consequence of this severe hypoperfusion/hypoxic event. Thus, epilepsy is much more than a disease hallmarked by seizures, since the occurrence of postictal hypoperfusion/hypoxia results in a separate set of neurological consequences that are currently not being treated and are preventable.
Article and author information
Author details
Gordon Campbell Teskey
Funding
Canadian Institutes of Health Research (MOP-130495)
- Gordon Campbell Teskey
Natural Sciences and Engineering Research Council of Canada (RGPIN/03819-2014)
- Gordon Campbell Teskey
Canadian Institutes of Health Research (MOP-136839)
- Paolo Federico
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jan-Marino Ramirez, Seattle Children's Research Institute and University of Washington, United States
Ethics
Animal experimentation: Rodents were handled and maintained according to the Canadian Council for Animal Care guidelines. These procedures were approved by the Life and Environmental Sciences Animal Care and Health Sciences Animal Care Committees at the University of Calgary (AC11-0073).
Human subjects: Human experimentation was approved by the University of Calgary's Conjoint Health Research Ethics Board (REB13-0571). All patients (or guardians of patients) provided written informed consent.
Version history
- Received: July 4, 2016
- Accepted: November 21, 2016
- Accepted Manuscript published: November 22, 2016 (version 1)
- Version of Record published: December 13, 2016 (version 2)
Copyright
© 2016, Farrell et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Postictal behavioural impairments are due to a severe prolonged hypoperfusion/hypoxia event that is COX-2 dependent
eLife 5:e19352.
https://doi.org/10.7554/eLife.19352
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