Hypoxic Preconditioning: The Multiplicity of Central Neurotransmitter Mechanisms and Method of Predicting Its Efficiency

Abstract

In rats, a single moderate hypobaric hypoxia (HBH) increased the resistance to severe hypoxia (SHBH). The HBH efficiency and neurotransmitter mechanisms of its preconditioning action were investigated by biochemical and pharmacological methods. It will be substantiated in the chapter: (1) HBH preconditioning has its own mechanisms that do not depend on an innate resistance to SHBH and prior hypoxic experience of rats; (2) the same preconditioning effect can be achieved by diverse neuronal pathways and synaptic plasticity means; (3) cholinergic and, presumably, serotoninergic, GABAergic and/or glutamatergic systems of the caudal brainstem, cortex and some other brain structures are involved in HBH realisation; (4) the rate of sensorimotor gating estimated in the model of acoustic startle pre-pulse inhibition (PPI) predicts the efficiency of hypoxic preconditioning and (5) the cholinergic system, including α7 nicotinic receptors, is involved in the mechanisms of HBH-PPI-dependent preconditioning effects.

Opposite Pathways of Cholinergic Mechanisms of Hypoxic Preconditioning in the Hippocampus: Participation of Nicotinic α7 Receptors and Their Association with the Baseline Level of Startle Prepulse Inhibition

“…The hypoxic models were used as before [ 20 , 45 ]. Varying severities of hypoxia were created in the pressure chambers.…”

“…It is known that nAChRs are involved in hypoxic or ischaemic preconditioning in the brain and other organs, and it was most convincingly demonstrated for the α7 and α4β2nAChRs [ 40 , 41 , 42 , 43 , 44 ]. In our experiments, PNU (but not RJR2403), and more pronouncedly its solvent dimethyl sulfoxide (DMSO, 2–3%), showed a PPI-associated effect on the efficiency of HBH, the direction of which changed to the opposite at the border when PPI = 36–40% [ 20 , 45 ]. At the concentrations used, DMSO showed anticholinesterase activity [ 46 ] and PNU (26 and 260 nmol/kg) exerted a desensitizing effect on α7 nAChRs [ 47 , 48 , 49 ].…”

“…However, studies of this kind on the models of hypoxic preconditioning in the caudal brainstem are rare and seem to be non-existent for the forebrain structures. In particular, cholinergic participation is detected in the majority of the functional sites of cardiorespiratory networks (see review in [ 20 ]). However, there were no data on the participation of cholinergic system in the cardiorespiratory networks under hypoxic preconditioning.…”

“…In our previous studies, we found that the cholinergic synaptic pool of the caudal brainstem and cortex was involved in hypoxic preconditioning. However, the functional meaning of the identified reactions for the mechanisms of adaptation was not clear in the intact (not undergone to severe hypoxia) rat group [ 20 , 26 ]. At the same time, we revealed a high rat-to-rat variability of HBH efficiency in resistance to severe hypoxia over a time span from 4 to 27 min [ 34 ].…”

“…It is known that the pronounced maximum concentration and high mRNA expression of nAChRs of this subtype are in the hippocampus [ 47 , 50 , 51 ]. At the same time, in the above biochemical experiments, the cholinergic synaptic pool of the hippocampus did not show any reaction to HBH [ 20 , 26 ].…”