Untitled

Abstract

Prophylactic transient hypoxia (preconditioning) increased neuron resistance to subsequent induction of severe hypoxia. Published data and results obtained by the authors on the molecular-cellular mechanisms of hypoxic preconditioning are presented. The roles of intracellular signal transduction, genome function, stress proteins, and neuromodulatory peptides in this process are discussed. The roles of glutamatergic as well as calcium and phosphoinositide regulatory systems and neuromodulatory factors as components of "volume" signal transmission are analyzed in hypoxic preconditioning-associated induction of functional tolerance mechanisms against the acute harmful effects of hypoxia on neurons in olfactory slices.

Current insights into the molecular mechanisms of hypoxic pre- and postconditioning using hypobaric hypoxia

“…In vitro models of cerebral hypoxic preconditioning include studies in hippocampal slices (Pérez-Pinzón et al, 1996 ; Bickler and Fahlman, 2009 ) and olfactory cortex (Semenov et al, 2002 ; Samoilov et al, 2003 ), as well as primary neuronal cultures (Arthur et al, 2004 ). It has been demonstrated that preconditioning with a single short (2 min) episode of anoxia in slices of the olfactory cortex or three trials of 1 min anoxia in the hippocampal slicesincreases the resistance of the cells to severe “test” anoxia, preventing depression of the evoked potential amplitudes and calcium overload associated with anoxic injury whereas moderate calcium load is required for induction of tolerance during anoxic preconditioning (Pérez-Pinzón et al, 1999 ; Semenov et al, 2012 ).…”

“…A central place in the studies of hypoxic preconditioning belongs to identification of its molecular mechanisms with special attention being paid both to their unique character and similarity with the mechanisms of ischemic preconditioning. The process of preconditioning can be divided into several phases starting with the phase of initiation of hypoxic tolerance (Samoilov, 1997 ; Samoilov et al, 2003 ) or the immediate phase of adaptation to hypoxia (Lukyanova et al, 2013 ) which covers the first few minutes following the exposure to moderate hypoxia. This acute stage is clearly linked with the launch of several molecular signaling processes.…”

“…This acute stage is clearly linked with the launch of several molecular signaling processes. The important mechanism which significantly contributes to the development of the later phases of brain hypoxic tolerance is obviously associated with the acute changes in neuronal redox state in favor of reduction equivalents that, in turn, can result in modifications of calcium bound to intracellular hydrophobic components (for review see Samoilov et al, 2003 ). Another key process at this stage is a remodeling of the respiratory mitochondrial chain and switching to the mitochondrial complex II, as well as rapid and transient activation of hypoxia-inducible factor HIF-1 (Lukyanova et al, 2009 , 2012 ).…”

“…The second phase of hypoxic preconditioning, the phase of induction of long-term hypoxic tolerance, involves significant alterations of the intracellular signal transduction processes, primarily modest activation of the glutamatergic, calcium, phosphoinositide, cyclic AMP regulatory systems (Semenov et al, 2000 , 2002 ; Samoilov et al, 2003 ) and rapid changes in pro- and antioxidant reactions (Ravati et al, 2000 : Furuichi et al, 2005 ). This is followed by fast protein kinase- and protease-dependent modifications of ion channels, receptors, redox-sensitive proteins, as well as triggering of the third phase—the phase of expression of hypoxic tolerance.…”