287 Hyperoxia Decreases, Injury Caused by Phorbolester Increases Vegf Expression in the Brain of Newborn Rats

Abstract

Objective: Vascular endothelial growth factor (VEGF) expression promotes angiogenesis and neuronal repair. The aim of this study was to investigate VEGF expression in relation to neurodegeneration, either caused by hyperoxia, a frequent problem in the treatment of preterm infants with respiratory dysfunction, or caused by brain injury, an important complication (e. g. In case of intracerebral haemorrhage) in the early neonatal period of immature newborns. Methods: 6 d old Wistar rat pups were either subjected to 80 % oxygen or treated with phorbolester. After 0, 2, 6, 12 and 24 h of exposition animals (n = 5 per group) were sacrificed and the brain cortices were processed for molecular experiments on RNA (quantitative RT-PCR) and protein (Western blot) levels using VEGF specific primers and antibodies. Results: In association with hyperoxia a decrease in VEGF mRNA expression down to about 25 % of the basal level of the control animals (no additional oxygen exposition) was noted. This effect was already evident at 2 h with a minimum of VEGF mRNA expression at 2 h and 6 h (p < 0.01). The protein expression also showed a decrease of VEGF signal associated with hyperoxia. The weakest signal appeared at 12 h (p < 0.01). In the case of phorbolester treatment we have seen an increase of VEGF expression up to about 200 % compared to the controls, with a maximum of mRNA at 6 h (p < 0.01) and a maximum of protein expression at 12 h and 24 h (p < 0.05). Conclusion: Exposure of newborn rats to hyperoxia induces a statistically significant time-dependent decrease, treatment with phorbolester a statistically significant time-dependent increase in VEGF expression in the cortices of the animals. These effects are evident on the transcriptional and translational level.