Glucocorticoid-Dependent Mechanisms of Brain Tolerance to Hypoxia

Adaptation of organisms to stressors is coordinated by the hypothalamic-pituitary-adrenal axis (HPA), which involves glucocorticoids (GCs) and glucocorticoid receptors (GRs). Although the effects of GCs are well characterized, their impact on brain adaptation to hypoxia/ischemia is still understudied. The brain is not only the most susceptible to hypoxic injury, but also vulnerable to GC-induced damage, which makes studying the mechanisms of brain hypoxic tolerance and resistance to stress-related elevation of GCs of great importance. Cross-talk between the molecular mechanisms activated in neuronal cells by hypoxia and GCs provides a platform for developing the most effective and safe means for prevention and treatment of hypoxia-induced brain damage, including hypoxic pre- and post-conditioning. Taking into account that hypoxia- and GC-induced reprogramming significantly affects the development of organisms during embryogenesis, studies of the effects of prenatal and neonatal hypoxia on health in later life are of particular interest. This mini review discusses the accumulated data on the dynamics of the HPA activation in injurious and non-injurious hypoxia, the role of the brain GRs in these processes, interaction of GCs and hypoxia-inducible factor HIF-1, as well as cross-talk between GC and hypoxic signaling. It also identifies underdeveloped areas and suggests directions for further prospective studies.

Automated summary

The adaptation of organisms to stressors is coordinated by the hypothalamic-pituitary-adrenal axis (HPA), involving glucocorticoids (GCs) and glucocorticoid receptors (GRs). Understanding the impact of GCs on brain adaptation to hypoxia/ischemia remains understudied, despite the vulnerability of the brain to hypoxic injury and GC-induced damage. Cross-talk between molecular mechanisms activated by hypoxia and GCs in neuronal cells presents potential for preventive and therapeutic approaches to hypoxia-induced brain damage.