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290 Genes Important in Inflammation, Apoptosis, Transcription Regulation and Angiogenesis are Induced in the Newborn Mouse Brain after Hypoxia-Reoxygenation (HR)
  1. AGW Rognlien1,2,
  2. EJ Wollen1,2,
  3. M Atneosen-Åsegg2,3,
  4. M Bjørås4,
  5. OD Saugstad1,2
  1. 1Department of Pediatric Research, Oslo University Hospital HF
  2. 2Women and Children’s Division, University of Oslo, Oslo
  3. 3Department of Clinical Molecular Biology and Laboratory Sciences, Akershus University Hospital, Lørenskog
  4. 4Department of Microbiology, Oslo University Hospital HF, Oslo, Norway

Abstract

Background and Aims Pathogenesis of birth asphyxia has yet to be fully elucidated. To explore the mechanism of HR injury we followed the temporal profile of a priori selected genes in the newborn mouse brain.

Methods 84 C57BL/6 mice (postnatal day 7) were randomized to 120 minutes of hypoxia (FiO2 0.08, n=64) or 180 minutes in air (controls (C21), n=20). The hypoxia group was randomized to 30 min reoxygenation with FiO2 0.60 (H60) or air (H21). After observation in air for 0, 150, 300 minutes or 3 days, organs were harvested. Homogenate of hippocampus and striatum was analyzed for mRNA expression of 44 genes by real-time PCR.

Results Lcn2, Mt1, Hmox1 and Vegfa were significantly up-regulated (p<0.05) after 0–300 min observation when comparing H21vsC21 and H60vsC21. Ccl2, Ccl12 and Tnf were up-regulated from 0–150 min, Stat3 from 150–300 min, while Ccnd1 was down-regulated at 0 min in both comparisons. In the H21vsC21 comparison at 0 min, Neil3 and Apaf1 were down-regulated. When comparing H60vsH21, Cxcl10 (0 min) and Hmox1 (300 min) were up-regulated while Neil3 (0 min) was down-regulated. There were no significant gene expression changes after 3 days.

Conclusions Genes important in inflammation (Lcn2, Mt1, Ccl2, Ccl12, Cxcl10, Tnf, Hmox1), apoptosis (Lcn2, Mt1, Tnf, Hmox1, Vegfa), angiogenesis (Vegfa), and transcription regulation (Stat3) were induced up to 300 minutes after hypoxia-reoxygenation while the DNA-glycosylase Neil3 was suppressed. The up-regulation of the pro-inflammatory cytokine Cxcl10 after hyperoxic compared to normoxic reoxygenation, confirms that hyperoxia induces additional inflammation.

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