Mild Hypoxia Postconditioning Induces Hypoxia-Inducible Factor 1 Alpha Expression and Improves the Neurobehavioral Abilities of Rats with Hypoxic-Ischemic Brain Damage

Abstract

Background: While severe hypoxia is known to contribute to neurotoxicity and lead to abnormal behavior, mild hypoxia may have beneficial effects mediated through endogenous adaptive responses. Objectives: The present study aimed to investigate the effects of mild hypoxia postconditioning and long-term neurobehavioral ability rehabilitation after hypoxic-ischemic brain damage (HIBD). Methods: Seven-day-old rats underwent left carotid ligation followed by 2 hours of hypoxia stress. Rats received different protocols of mild hypoxia postconditioning for 5 days and underwent neurobehavioral testing during the last week of the study. Hypoxia-inducible factor 1 alpha (HIF-1a) expression was assessed, and neurobehavioral ability assays were performed. Results: Compared with the HIBD group, rats postconditioning with mild hypoxia showed increased HIF-1a expression, and their brain functions were better in neurobehavioral analyses. The rehabilitation of brain functions may be associated with high HIF-1a expression and better behavioral performance. Conclusions: Our findings indicate that mild hypoxia postconditioning improves neurobehavioral ability, and HIF-1a may be a potential mediator of the observed effects. Our findings suggest that there may be clinical implications for treating infants with HIBD.