title: Transcriptome profiling of the newborn mouse brain after hypoxia-reoxygenation: hyperoxic reoxygenation induces inflammatory and energy failure responsive genes.
abstract: BACKGROUND
  Supplemental oxygen used during resuscitation can be detrimental to the newborn brain. The aim was to determine how different oxygen therapies affect gene transcription in a hypoxia-reoxygenation model.
  
  
  METHODS
  C57BL/6 mice (n = 56), postnatal day 7, were randomized either to 120 min of hypoxia 8% O2 followed by 30 min of reoxygenation with 21, 40, 60, or 100% O2, or to normoxia followed by 30 min of 21 or 100% O2. Affymetrix 750k expression array was applied with RT-PCR used for validation. Histopathology and immunohistochemistry 3 d after hypoxia-reoxygenation compared groups reoxygenated with 21 or 100% O2 with normoxic controls (n = 22).
  
  
  RESULTS
  In total, ~81% of the gene expression changes were altered in response to reoxygenation with 60 or 100% O2 and constituted many inflammatory-responsive genes (i.e., C5ar2, Stat3, and Ccl12). Oxidative phosphorylation was downregulated after 60 or 100% O2. Iba1(+) cells were significantly increased in the striatum and hippocampal CA1 after both 21 and 100% O2.
  
  
  CONCLUSIONS
  In the present model, hypoxia-reoxygenation induces microglial accumulation in subregions of the brain. The transcriptional changes dominating after applying hyperoxic reoxygenation regimes include upregulating genes related to inflammatory responses and suppressing the oxidative phosphorylation pathway.
authors.affiliation: Department of Pediatric Research, Clinic of Women and Child Health, Oslo University Hospital, Rikshospitalet, University of Oslo, Oslo, Norway.
authors.forename: Embjørg J
authors.initials: EJ
authors.lastname: Wollen
authors.affiliation: 1] Department of Pediatric Research, Clinic of Women and Child Health, Oslo University Hospital, Rikshospitalet, University of Oslo, Oslo, Norway [2] Department of Microbiology and CMBN, University of Oslo, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Yngve
authors.initials: Y
authors.lastname: Sejersted
authors.affiliation: Department of Pediatric Research, Clinic of Women and Child Health, Oslo University Hospital, Rikshospitalet, University of Oslo, Oslo, Norway.
authors.forename: Marianne S
authors.initials: MS
authors.lastname: Wright
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Polish-American Children's Hospital, Jagiellonian University, Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Madetko-Talowska
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Polish-American Children's Hospital, Jagiellonian University, Krakow, Poland.
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Bik-Multanowski
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Polish-American Children's Hospital, Jagiellonian University, Krakow, Poland.
authors.forename: Przemko
authors.initials: P
authors.lastname: Kwinta
authors.affiliation: Norwegian Computing Center, Oslo, Norway.
authors.forename: Clara-Cecilie
authors.initials: CC
authors.lastname: Günther
authors.affiliation: Bioinformatics Core Facility, Institute for Medical Informatics, University of Oslo, Oslo University Hospital, Oslo, Norway.
authors.forename: Ståle
authors.initials: S
authors.lastname: Nygård
authors.affiliation: Department of Pathology, Oslo University Hospital, Ullevaal, Oslo, Norway.
authors.forename: Else Marit
authors.initials: EM
authors.lastname: Løberg
authors.affiliation: Department of Pediatric Research, Clinic of Women and Child Health, Oslo University Hospital, Rikshospitalet, University of Oslo, Oslo, Norway.
authors.forename: Martin B
authors.initials: MB
authors.lastname: Ystgaard
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Polish-American Children's Hospital, Jagiellonian University, Krakow, Poland.
authors.forename: Jacek J
authors.initials: JJ
authors.lastname: Pietrzyk
authors.affiliation: Department of Pediatric Research, Clinic of Women and Child Health, Oslo University Hospital, Rikshospitalet, University of Oslo, Oslo, Norway.
authors.forename: Ola D
authors.initials: OD
authors.lastname: Saugstad
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D016000:Cluster Analysis; D004734:Energy Metabolism / Q000235:genetics; D020869:Gene Expression Profiling; D018496:Hyperoxia / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D059467:Transcriptome