The Acoustic Sensorimotor Gating Predicts the Efficiency of Hypoxic Preconditioning. Participation of the Cholinergic System in This Phenomenon

Elena I Zakharova,Mikhail Yu Monakov,Zinaida I Storozheva,Andrew T Proshin,Alexander M Dudchenko

doi:10.4236/jbise.2018.111002

Abstract

Moderate one-off hypobaric hypoxia (HBH) provokes preconditioning and prolongs the resistance (T, the time before apnoea) to severe hypobaric hypoxia (SHBH). Hypoxic preconditioning has therapeutic potential; however, the efficiency of hypoxic preconditioning varies greatly and the methods for its preliminary evaluation are absent in both animals and humans. This rodent study evaluates the dependence of SHBH resistance, initiated by HBH, on the rate of sensorimotor gating estimated in the model of the acoustic startle prepulse inhibition (PPI). A stable negative correlation was found between PPI and T. Low doses of the α7 nicotinic receptor agonist, PNU-282987 (PNU), and more pronouncedly dimethyl sulfoxide (DMSO) (a PNU solvent), inverted the correlation between PPI and T from negative to positive. The DMSO and PNU effects were reversed at PPIs of 0.36 - 0.40 (36% - 40%). DMSO increased T values by 52.2% ± 9.7% in the region of lower HBH efficiency (PPI ≥ 0.40) and reduced it by 35.2% ± 9.3% in the region of higher HBH efficiency (PPI < 0.40). PNU reduced both DMSO effects. The involvement of the central cholinergic mechanisms was substantiated in both DMSO and PNU influences on HBH. In conclusion, 1) PPI can be used to predict the efficiency of hypoxic preconditioning and to study its mechanisms, 2) two opposite cholinergic PPI-related mechanisms participate in the preconditioning effects of HBH, 3) the sensitivity of rats to DMSO and PNU diverges when the PPI is 0.36 - 0.40, and 4) DMSO can enhance resistance to severe hypoxia in the region of the lower preconditioning efficiency of HBH at PPI ≥ 0.4.

Highlights

Hypoxic and ischaemic preconditioning, in which hypoxia is the main adaptive factor, mobilise the body’s protection and thereby prevent or reduce the pathogenesis of severe hypoxia or ischaemic stroke in organs and tissues [1,2,3,4]
This study investigates the cholinergic nicotinic mechanisms of hypobaric hypoxia (HBH) preconditioning in rats using pharmacological experiments with the α7 nAChRs selective agonist, PNU-282,987 (PNU), in a solution of dimethyl sulfoxide (DMSO) in the prepulse inhibition (PPI) model
Using the PPI model for preliminary evaluation of the acoustic sensorimotor gating, a PPI-T test was developed to predict the efficiency of HBH preconditioning in animals

Summary

Introduction

In which hypoxia is the main adaptive factor, mobilise the body’s protection and thereby prevent or reduce the pathogenesis of severe hypoxia or ischaemic stroke in organs and tissues [1,2,3,4]. Moderate one-off hypobaric hypoxia (HBH; 11% O2 for 60 min) provokes preconditioning and increases the resistance to severe hypobaric hypoxia (SHBH; 4.5% O2). In other words, it prolongs the time (T) before the onset of apnoea in SHBH conditions [5,6,7]. The problem appears to be the absence of methods for the preliminary evaluation of the efficiency of hypoxic preconditioning. The efficiency of the preconditioning effects of HBH could be based on different mechanisms, and knowledge of these different mechanisms could be significant for both fundamental and practical medicine

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