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Antiepileptic drugs prevent seizures in hyperbaric oxygen: A novel model of epileptiform activity.

Abstract：

:Breathing oxygen at sufficiently elevated pressures can trigger epileptiform seizures. Therefore, we tested the hypothesis that pre-treatment with FDA-approved antiepileptic drugs could prevent seizure onset in hyperoxia at 5 atmospheres absolute. We selected drugs from two putative functional categories, Na+-channel antagonists and GABA enhancers, each administered intraperitoneally at four doses in separate groups of C57BL/6 mice. The drugs varied in efficacy at the doses used. Of the five tested Na+-channel antagonists, carbamazepine and lamotrigine more than tripled seizure latency compared to values seen in vehicle controls. Primidone, zonisamide and oxcarbazepine were less effective. Of the four GABA reuptake inhibitors, tiagabine and vigabatrin also increased seizure latency by more than three times control values; valproic acid was less effective, and the GABA synthesis promoter gabapentin was intermediate in effectiveness. We infer that Na+-channel function and GABA neurotransmission may be critical targets in the pathophysiology of CNS O2 toxicity. Because these essential components of neuronal excitation and inhibition are also implicated in the pathogenesis of other seizure disorders, including generalized epilepsy, we propose that, at some level, common pathways are involved in these pathologies, although the initiating insults differ. Furthermore, hyperoxic exposures are not known to cause the spontaneously-recurring seizures that characterize true clinical epilepsy. Nonetheless, experimental studies of hyperbaric oxygen toxicity could provide new insights into molecular mechanisms of seizure disorders of various etiologies. In addition, the neuropathology of hyperbaric oxygen is particularly relevant to the hypothesis held by some investigators that oxidative stress is an etiological factor in clinical epilepsies.

journal_name

Brain Res

journal_title

Brain research

authors

Demchenko IT,Zhilyaev SY,Moskvin AN,Krivchenko AI,Piantadosi CA,Allen BW

doi

10.1016/j.brainres.2016.12.032

subject

Has Abstract

pub_date

2017-02-15 00:00:00

pages

347-354

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(16)30861-7

journal_volume

1657

pub_type

杂志文章

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Antiepileptic drugs prevent seizures in hyperbaric oxygen: A novel model of epileptiform activity.