Блокада транспортеров гамма-аминомасляной кислоты в синапсах головного мозга предохраняет от развития судорог при дыхании кислородом под давлением

Abstract

Hyperbaric oxygen (HBO2) causes inhibition of gamma-aminobutyric acid (GABA) synthesis in the brain, which leads to a decrease in GABAergic neurotransmission and the development of convulsive syndrome like epileptic seizures. We tested the hypothesis that inhibition of GABA transporters can compensate a decrease in GABA synthesis, enhance GABAergic transmission, and prevent against oxygen seizures. HBO2-induced seizures were analyzed in awake rats pretreated with GABA transporter inhibitors (NO-711, nipecotic acid) by intracerebroventricular injection and exposed to oxygen at 5 ATA (absolute atmospheres). In a separate group of rats, GABA was measured in the striatum using intracerebral microdialysis coupled with liquid chromatography. Inhibition of neuronal and glial GABA transporters increased extracerebral GABA content in the brain and protected against HBO2-induced seizures. A more effective anti-convulsive effect was observed after the treatment with a non-selective inhibitor of GABA transporters. The data obtained indicate that blocking the functions of neuronal and glial GABA transporters increases the level of extracellular GABA in the brain and prevent the development of convulsive syndrome in HBO2. The anti-convulsive effects of the GABA transporter inhibition in HBO2 are apparently due to the enhancement of GABA-mediated synaptic and extrasynaptic neurotransmissions. Inhibition of GABA transporters may be a promising approach for the development of effective methods to prevent oxygen seizures.