title: Postictal behavioural impairments are due to a severe prolonged hypoperfusion/hypoxia event that is COX-2 dependent.
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< 10 mmHg) 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.
authors.affiliation: Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Farrell
authors.affiliation: Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: Ismael
authors.initials: I
authors.lastname: Gaxiola-Valdez
authors.affiliation: Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: Marshal D
authors.initials: MD
authors.lastname: Wolff
authors.affiliation: Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: Laurence S
authors.initials: LS
authors.lastname: David
authors.affiliation: Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.|Department of Physiology, Catholic University of Health and Allied Sciences, Mwanza, Tanzania.
authors.forename: Haruna I
authors.initials: HI
authors.lastname: Dika
authors.affiliation: Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: Bryce L
authors.initials: BL
authors.lastname: Geeraert
authors.affiliation: Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: X
authors.initials: X
authors.lastname: Rachel Wang
authors.affiliation: Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: Shaily
authors.initials: S
authors.lastname: Singh
authors.affiliation: Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Spanswick
authors.affiliation: Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: Jeff F
authors.initials: JF
authors.lastname: Dunn
authors.affiliation: Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Antle
authors.affiliation: Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: Paolo
authors.initials: P
authors.lastname: Federico
authors.affiliation: Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: G Campbell
authors.initials: GC
authors.lastname: Teskey
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000503:physiopathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D000860:Hypoxia / Q000473:pathology*; D020318:Rats, Long-Evans; D012640:Seizures / Q000150:complications*
chemical_list: D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat
keywords: behavioural dysfunction; epilepsy; human; hypoperfusion; hypoxia; mouse; neuroscience; rat; seizures