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.

Keywords

behavioural dysfunction, epilepsy, human, hypoperfusion, hypoxia, mouse, neuroscience, rat, seizures

Citation

Farrell JS1, Gaxiola-Valdez I1, Wolff MD1, David LS1, Dika HI1,2, Geeraert BL1, Rachel Wang X1, Singh S1, Spanswick SC1, Dunn JF1, Antle MC1, Federico P1, Teskey GC1. (2016). Postictal behavioural impairments are due to a severe prolonged hypoperfusion/hypoxia event that is COX-2 dependent. eLife 2016;5:e19352

URI

http://hdl.handle.net/1880/51855

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