GABAergic Mechanisms of Brain Tolerance to Hypoxia in Lower Vertebrates

Hypoxic/ischemic brain injuries are a major medical challenge.One of the approaches to the development of therapeutic interventionsis elucidating the neuronal survival pathways in O-2 deficiency-tolerantvertebrates, which could suggest the ways to mitigate a hypoxia-induced catastrophein individual nerve cells under conditions of oxygen starvation.Metabolic depression is considered a universal survival strategyfor hypoxia-tolerant animals; however, the ins and outs of the mechanismthat imposes limitations on brain metabolism when PO2 decreasesare still unknown. Under oxygen starvation, an increase in the extracellularconcentration of inhibitory neurotransmitters can be one of thesignificant links in the apparatus for electrical activity suppression,which makes it possible to reduce energy consumption. GABA (gamma-aminobutyricacid) serves as a universal inhibitory neurotransmitter in the CNSof higher and lower vertebrates, whose functioning is attributedto metabolic suppression and leveling of energy failure consequences. GABAis found in various vertebrate taxa. This review addresses the strategiesof GABA involvement in the mechanisms that ensure brain toleranceto oxygen starvation in members of various taxonomic groups of lowervertebrates (cyclostomes, cartilaginous and bony fish, amphibians,reptiles) distinguished by a most prominent ability to survive underacute and chronic hypoxia-anoxia.