Brain hypoxia and ischemia: new insights into neurodegeneration and neuroprotection

Impaired oxygen (hypoxia) or reduced blood flow (ischemia) to the brain is a major cause of morbidity and mortality in humans resulting in cognitive impairment, seizures, and other neurological disabilities. Ischaemic stroke is the third leading cause of death in Western countries, behind only heart disease and cancer. Hypoxia is known to have a significant effect on cellular functions with an immediate response by membrane lipids and enzymes and with long-term changes in gene expression and levels of protein synthesis. Much data has accumulated to suggest that vascular factors and the levels of oxygen supply to the brain are linked with pathogenesis of various neurodegenerative disorders, in particular, of Alzheimer’s disease (AD), and their progression. Brain hypoxia also affects behavioural and cognitive abilities, e.g. learning and memory, of individuals and their neurological status. Hypoxia during the prenatal period or in labour affects significantly brain development and functions in later life and predisposes to various cognitive abnormalities.


Although there are numerous studies of the molecular mechanisms underlying effects of hypoxia and ischemia there are still no pharmacological treatments available to reduce cell death in the ischaemic/hypoxic brain. Endogenously, the central nervous system can withstand cerebral hypoxia or ischemia for a limited amount of time, a phenomenon called primary hypoxic–ischaemic tolerance. With an appropriate time interval and dosage, when a non-injurious hypoxic exposure (known as preconditioning) is performed before a potentially lethal hypoxic–ischaemic stress, tolerance can be increased and cells protected. Furthermore, the hypoxic preconditioning-induced neuronal tolerance appears to be universal and represents increased resistance not only to hypoxic/ischaemic insults but also to other injurious factors including various types of stress. Although little is still known about the mechanisms of hypoxic preconditioning, however, a recent genomic study identified a number of genes which may contribute to hypoxia-induced tolerance.


This Research Topic aims at a multifaceted approach to evaluate recent progress in our understanding of the effects of hypoxia and ischemia on the brain at the molecular, morphological and physiological levels and how preconditioning by intermittent mild hypoxia can protect the brain improving its functioning and reducing pathology.


The research articles and review papers are encouraged from scientists working in the areas of i) brain membrane biochemistry, including lipids and proteins; ii) molecular biology (effect of hypoxia and ischemia on gene expression, role of miRNAs); iii) morphological analysis of brain structure after hypoxia or ischemia; iv) studies of membrane channels and processing of complex membrane proteins such as the amyloid precursor protein; v) changes in expression and functions of matrix metalloproteases, as well as amyloid-degrading enzymes and other proteins involved in amyloid clearance; vi) perivascular status of the brain and functions of the blood brain barrier; vii) role of hypoxia and ischemia in development of cognitive functions and neurological disorders; viii) protective mechanism of hypoxic preconditioning and its possible therapeutic applications

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