Inhibition of GABA-Transaminase and GABA-Transporters in the Brain by Vigabatrin and Tiagabine Prevents Seizure Development in Rats Breathing Hyperbaric Oxygen.

Hyperbaric oxygen (HBO2) inhibits the GABAergic function in the brain, leading to the development of convulsive reactions in the form of paroxysmal discharges on the EEG, as well as movement disorders, in a manner similar to a generalized epileptic seizure. We hypothesize that HBO2-induced deficiency of GABAergic neurotransmission due to suppression of GABA synthesis, can be overcome by blocking GABA clearance from the synaptic cleft and slowing down its enzymatic degradation. The present study aimed to explore the development of seizures in rats at 5 ATA of oxygen pressure after tiagabine-mediated blockade of GABA transporters and vigabatrin-mediated inhibition of GABA-transaminase. The data obtained in this study are as follows: (1) both vigabatrin-mediated inhibition of GABA transaminase and tiagabine-mediated inhibition of GABA transporters prevented the development of seizures in rats at 5 ATA of oxygen pressure; (2) HBO2-induced oxygen seizures arose with a decrease in the brain GABA concentration by 30–40% vs. the basal level; (3) vigabatrin-mediated inhibition of GABA transaminase prevented a decrease in the rat striatum GABA level at 5 ATA of oxygen pressure. Thus, a slowdown in synaptic GABA clearance or attenuation of enzymatic GABA degradation can compensate an HBO2-induced reduction in GABA synthesis, as well as raise the GABA concentration to a level sufficient for the restoration of GABAergic function, preventing thereby the development of convulsive syndrome. [ABSTRACT FROM AUTHOR]