Hypoxia Supports LPS-Driven Tolerance and Functional Activation in BV-2 Microglial Cells

BACKGROUND: Prolonged hypoxia contributes to irreversible organ damage, particularly in the brain and heart. While chronic hypoxia is harmful, mild short-term hypoxia can trigger protective mechanisms. This study investigates how such hypoxic conditions affect BV-2 tolerant microglial cells in vitro, focusing on inflammation, metabolism, and functional activity. Although in vitro models provide a controlled setting, our findings may offer insights into microglial behavior in vivo under similar conditions. METHODS: We used various molecular and biochemical techniques to assess the inflammatory state of BV-2 microglia under hypoxia, measuring glycolytic activity (via lactate production), and evaluating migratory and phagocytic capacities in vitro. RESULTS: Hypoxic conditions induced a more tolerant, anti-inflammatory phenotype in BV-2 cells, with decreased pro-inflammatory mediators and reduced glycolytic activity, regulated by the MyD88/NF-κB p65 pathway. Tolerance supports increased migration and phagocytosis, but under hypoxic conditions, these effects were significantly declined compared to normoxic conditions, mediated through the ERK1/2 pathway. CONCLUSIONS: These findings suggest that short-term hypoxia may regulate microglial behavior and restore homeostasis, with implications for neuroinflammatory conditions.