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This review is devoted to the phenomenon of intermittent hypoxic training and is aimed at drawing the attention of researchers to the necessity of studying the mechanisms mediating the positive, particularly neuroprotective, effects of hypoxic training at the molecular level. The review briefly describes the historical aspects of studying the beneficial effects of mild hypoxia, as well as the use of hypoxic training in medicine and sports. The physiological mechanisms of hypoxic adaptation, models of hypoxic training and their effectiveness are summarized, giving examples of their beneficial effects in various organs including the brain. The review emphasizes a high, far from being realized at present, potential of hypoxic training in preventive and clinical medicine especially in the area of neurodegeneration and age-related cognitive decline. [ABSTRACT FROM AUTHOR]

Highlights from the article: Impaired oxygen supply (hypoxia) or reduced blood flow (ischemia) to the brain causes significant metabolic changes in neuronal and non-neural cells. The Research Topic "Brain hypoxia and ischemia: new insights into neurodegeneration and neuroprotection" evaluates recent progress in our understanding of the effects of hypoxia and ischemia on the brain at the molecular, morphological, and physiological levels. The authors suggest that alternate breathing or yogic intervention techniques can be considered as important non-invasive measures to protect the brain against hypoxia-associated pathology and discuss its efficacy for treatment of such neurodegenerative disease as AD.

Exposure of organisms to repetitive mild hypoxia results in development of brain hypoxic/ischemic tolerance and cross-tolerance to injurious factors of a psycho-emotional nature. Such preconditioning by mild hypobaric hypoxia functions as a "warning" signal which prepares an organism, and in particular the brain, to subsequent more harmful conditions. The endogenous defense processes which are mobilized by hypoxic preconditioning and result in development of brain tolerance are based on evolutionarily acquired gene-determined mechanisms of adaptation and neuroprotection. They involve an activation of intracellular cascades including kinases, transcription factors and changes in expression of multiple regulatory proteins in susceptible areas of the brain. On the other hand they lead to multilevel modifications of the hypothalamic-pituitary-adrenal endocrine axis regulating various functions in the organism. All these components are engaged sequentially in the initiation, induction and expression of hypoxia-induced tolerance. A special role belongs to the epigenetic regulation of gene expression, in particular of histone acetylation leading to changes in chromatin structure which ensure access of pro-adaptive transcription factors activated by preconditioning to the promoters of target genes. Mechanisms of another, relatively novel, neuroprotective phenomenon termed hypoxic postconditioning (an application of mild hypoxic episodes after severe insults) are still largely unknown but according to recent data they involve apoptosis-related proteins, hypoxia-inducible factor and neurotrophins. The fundamental data accumulated to date and discussed in this review open new avenues for elaboration of the effective therapeutic applications of hypoxic pre- and postconditioning. [ABSTRACT FROM AUTHOR]