Abstract
Background:
Hyperoxic reoxygenation following hypoxia increases the expression of inflammatory genes in the neonatal mouse brain. We have therefore compared the temporal profile of 44 a priori selected genes after hypoxia and hyperoxic or normoxic reoxygenation.
Methods:
Postnatal day 7 mice were subjected to 2 h of hypoxia (8% O2) and 30 min reoxygenation with 60% or 21% O2. After 0 to 72 h observation, mRNA and protein were examined in the hippocampus and striatum.
Results:
There were significantly higher gene expression changes in six genes after hyperoxic compared to normoxic reoxygenation. Three genes had a generally higher expression throughout the observation period: the inflammatory genes Hmox1 (mean difference: 0.52, 95% confidence interval (CI): 0.15–1.01) and Tgfb1 (mean difference: 0.099, CI: 0.003–0.194), and the transcription factor Nfkb1 (mean difference: 0.049, CI: 0.011–0.087). The inflammatory genes Cxcl10 and Il1b, and the DNA repair gene Neil3, had a higher gene expression change after hyperoxic reoxygenation at one time point only. Nineteen genes involved in inflammation, transcription regulation, apoptosis, angiogenesis, and glucose transport had significantly different gene expression changes with time in all intervention animals.
Conclusion:
We confirm that hyperoxic reoxygenation induces a stronger inflammatory gene response than reoxygenation with air.
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Acknowledgements
The authors want to express their sincere gratitude to Grethe Dyrhaug and Maren Bakkebø for technical assistance; the staff at Comparative Medicine, Oslo University Hospital; Are Hugo Pripp for statistical assistance; and Anna Frengen, Tonje Sonerud, and the Epigen laboratory at the Department of Clinical Molecular Biology and Laboratory Sciences, Akershus University Hospital, for generously lending us equipment and their assistance in running TaqMan array microfluidic card.
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Rognlien, A., Wollen, E., Atneosen-Åsegg, M. et al. Increased expression of inflammatory genes in the neonatal mouse brain after hyperoxic reoxygenation. Pediatr Res 77, 326–333 (2015). https://doi.org/10.1038/pr.2014.193
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DOI: https://doi.org/10.1038/pr.2014.193
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