Increased expression of inflammatory genes in the neonatal mouse brain after hyperoxic reoxygenation

Pediatr Res. 2015 Feb;77(2):326-33. doi: 10.1038/pr.2014.193. Epub 2014 Nov 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Apoptosis / genetics
  • Corpus Striatum / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation / physiology*
  • Heme Oxygenase-1 / metabolism
  • Hippocampus / metabolism*
  • Hyperoxia / metabolism*
  • Hypoxia / physiopathology*
  • Inflammation / genetics
  • Inflammation / metabolism*
  • Membrane Proteins / metabolism
  • Mice
  • NF-kappa B p50 Subunit / metabolism
  • Oxygen / administration & dosage
  • Oxygen / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Membrane Proteins
  • NF-kappa B p50 Subunit
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta1
  • Nfkb1 protein, mouse
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Oxygen