Postnatal Exposure to Brief Hypoxia Alters Brain VEGF Expression and Capillary Density in Adult Mice

Abstract

Perinatal hypoxia leads to changes in cerebral angiogenesis and persistent structural and functional changes in the adult brain. It may also result in greater vulnerability to subsequent challenges. We investigated the effect of postnatal day 2 (P2) hypoxic preconditioning on adult brain capillary density and brain vascular endothelial growth factor (VEGF) expression in mice. P2 mice were exposed to hypoxia (5% O2) in a normobaric chamber for 2 h then returned to normoxia while their littermates remained in normoxia (P2 control). After 2–6 months, they were euthanised and their brains were removed for capillary density determination. Another set of animals (P2 hypoxic mice and P2 controls) were euthanised at 2, 10, 23, and 60 days after birth and brain VEGF expression was assessed by western blot. Adult brain capillary density was significantly increased in the P2 hypoxic mice when compared to the P2 control mice. Additionally, VEGF expression appeared to be elevated in the P2-hypoxia mice when compared to the P2-control mice at all time points, and VEGF levels in P2-hypoxia mice declined with age similarly to P2-control mice. These data demonstrate that transient early-postnatal hypoxic stress leads to an increase in capillary density that persists in the adult, possibly due to increased VEGF expression. These results might be explained by epigenetic factors in the VEGF gene.