The Role of GABA Receptors in Seizure Development When Breathing Hyperbaric Oxygen

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The use of hyperbaric oxygen (HBO2) in medicine and in underwater diving is associated with the risk of its toxic (convulsant) effect on the central nervous system, the pathophysiological mechanisms of which have not been sufficiently studied. A common hypothesis about the mechanism of HBO2-induced convulsions is the idea that extreme hyperoxia suppresses GABAergic function with subsequent increase in CNS excitation, leading to convulsions. The deficit of GABAergic function in HBO2 is due to a decrease in the synthesis of the mediator, while the involvement of other components of inhibitory neurotransmission, in particular, GABA receptors, remains unclear. The aim of this work was to study the involvement of GABA receptors in the development of hyperbaric oxygen convulsions. In the course of the work, motor convulsions in HBO2 were assessed in rats that were injected with GABA receptor agonists: muscimol or baclofen into the lateral ventricle of the brain before hyperoxic exposure. The affinity of GABA receptors to these drugs was also assessed against the background of an increased level of cerebral GABA caused by intraventricular administration of nipecotic acid. New data from the studies are: (a) activation of GABA-A receptors with muscimol delayed the onset of seizures in HBO2, (b) the GABA-B receptor agonist baclofen weakened the development of hyperbaric oxygen seizures, but its anticonvulsant effect was reliably lower than that of muscimol, (c) the anticonvulsant efficacy of muscimol and baclofen was preserved with an increase in extracellular GABA caused by inhibition of GABA transporters with nipecotic acid. The affinity of GABA-A and GABA-B receptors to the inhibitory neurotransmitter did not change under conditions of hyperbaric hyperoxia.

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Sobre autores

O. Alekseeva

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Autor responsável pela correspondência
Email: osa72@inbox.ru
Rússia, St. Petersburg

T. Platonova

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Email: osa72@inbox.ru
Rússia, St. Petersburg

I. Demchenko

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Email: osa72@inbox.ru
Rússia, St. Petersburg

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2. Fig. 1. Time of onset of generalized seizures in rats under oxygen pressure of 5 ATA after the introduction of artificial cerebrospinal fluid (CSF), muscimol (MCM) and baclofen (BLF) into the cerebral ventricle.

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3. Fig. 2. Latent period of seizure onset in rats under 5 ATA oxygen pressure after intracerebral ventricular administration of artificial cerebrospinal fluid (CSF), baclofen (BLF), and muscimol (MCM). * – p < 0.05, compared with CSF; # – p < 0.01, compared with CSF and BLF.

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4. Fig. 3. Latent period of seizure onset in rats under oxygen pressure of 5 ATA after separate and combined intraventricular administration of baclofen (BLF), muscimol (MCM) and nipecotic acid (NPA). * – p < 0.01, compared with BLF; # – p < 0.05 compared with MCM and NPA.

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5. Fig. 4. Dynamics of GABA level in the striatum of rats breathing oxygen at a pressure of 5 ATA after the introduction of artificial cerebrospinal fluid (CSF), muscimol (MCM) or nipecotic acid (NPA) into the cerebral ventricle. Dotted line: GABA level in the striatum of the control group of animals (breathing atmospheric air); * – p < 0.05 in relation to the control level.

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