Intermittent Hypobaric Hypoxic Preconditioning Provides Neuroprotection by Increasing Antioxidant Activity, Erythropoietin Expression and Preventing Apoptosis and Astrogliosis in the Brain of Adult Rats Exposed to Acute Severe Hypoxia

Abstract

Background: Exposure to intermittent hypoxia has been demonstrated to be an efficienttool for hypoxic preconditioning, preventing damage to cells and demonstrating therapeutic benefits.We aimed to evaluate the effects of respiratory intermittent hypobaric hypoxia (IHH) to avoid braininjury caused by exposure to acute severe hypoxia (ASH). Methods: biomarkers of oxidative damage,mitochondrial apoptosis, and transcriptional factors in response to hypoxia were assessed by Westernblot and immunohistochemistry in brain tissue. Four groups of rats were used: (1) normoxic (NOR),(2) exposed to ASH (FiO27% for 6 h), (3) exposed to IHH for 3 h per day over 8 days at 460 mmHg,and (4) ASH preconditioned after IHH. Results: ASH animals underwent increased oxidative-stress-related parameters, an upregulation in apoptotic proteins and had astrocytes with phenotype formscompatible with severe diffuse reactive astrogliosis. These effects were attenuated and even preventedwhen the animals were preconditioned with IHH. These changes paralleled the inhibition of NF-κBexpression and the increase of erythropoietin (EPO) levels in the brain. Conclusions: IHH exertedneuroprotection against ASH-induced oxidative injury by preventing oxidative stress and inhibitingthe apoptotic cascade, which was associated with NF-κB downregulation and EPO upregulation