290 Genes Important in Inflammation, Apoptosis, Transcription Regulation and Angiogenesis are Induced in the Newborn Mouse Brain after Hypoxia-Reoxygenation (HR). (October 2012)

• Record Type: Journal Article
• Authors: Rognlien, AGW; Wollen, EJ; Atneosen-Åsegg, M; Bjørås, M; Saugstad, OD
• Is Part Of: Archives of disease in childhood. Volume 97(2012)Supplement 2
• Page Start: A85
• Page End: A85
• Publication Date: 2012-10
• Subjects: Children -- Diseases -- Periodicals; Infants -- Diseases -- Periodicals; 618.920005
• DOI: 10.1136/archdischild-2012-302724.0290
• Languages: English
• ISSNs: 0003-9888

Abstract

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 (H2 1). 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 H2 1vsC21 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 H2 1vsC21 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.