GABAergic Mechanisms of the Brain Tolerance to Hypoxia in Lower Vertebrates

Abstract

Hypoxic/ischemic brain injuries a major medical challenge. One of the approaches to the development of therapeutic interventions is to establish the pathways of survival for neurons in tolerant to O2 deficiency vertebrates, which could suggest the ways to mitigate hypoxic catastrophe for separate cells under oxygen starvation. Metabolic depression is considered to be a universal strategy for the survival of hypoxia tolerant animals; however, the details of the mechanism of brain metabolism limitation with a decrease in PO2 have not hitherto been established. Under oxygen starvation, an increase in the extracellular concentration of inhibitory neurotransmitters can be one of the significant links in the apparatus for suppression of electrical activity, which makes it possible to reduce energy demand. GABA (γ-aminobutyric acid) serves as a universal inhibitory neurotransmitter in the CNS of higher and lower vertebrates, the functioning of which is associated with the metabolism suppression and leveling the consequences of an energy failure. GABA is found in various taxonomic groups of vertebrates. This review considers strategies for GABA involvement in the mechanisms of ensuring a brain tolerance to oxygen starvation in representatives of various taxonomic groups of lower vertebrates (cyclostomes, cartilaginous and bony fish, amphibians, reptiles), which are distinguished by a most pronounced ability to survive under acute and chronic hypoxia/anoxia.