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Temporal Profile of Circulating microRNAs after Global Hypoxia-Ischemia in Newborn Piglets

Authors
  • Garberg, Håvard Tetlie
  • Huun, Marianne U.
  • Baumbusch, Lars O.
  • Åsegg-Atneosen, Monica
  • Solberg, Rønnaug
  • Saugstad, Ola Didrik
Type
Published Article
Journal
Neonatology
Publisher
S. Karger AG
Publication Date
Oct 18, 2016
Volume
111
Issue
2
Pages
133–139
Identifiers
DOI: 10.1159/000449032
PMID: 27750254
Source
Karger
Keywords
License
Green
External links

Abstract

Background: There is a lack of reliable biomarkers that can identify and grade acute hypoxic-ischemic encephalopathy in newborns. MicroRNAs (miRNA) are short, non-coding strands of RNA that are released into the circulation in response to tissue stress and injury. Some miRNAs are highly tissue specific and thus may potentially be non-invasive biomarkers of neonatal hypoxic-ischemic brain injury. Objective: The aim of this study was to characterize the temporal expression of selected circulating miRNAs in a clinically relevant piglet model of neonatal hypoxia-ischemia (HI). Methods: A total of 13 anesthetized newborn piglets were randomized to either a control group (n = 5) or transient global HI group (n = 8). HI was achieved by ventilation with 8% oxygen until the point of severe acidosis (arterial base excess ≤-20 mmol/l) and/or hypotension (mean arterial blood pressure ≤20 mm Hg) was reached. Plasma was sampled at baseline, at the end of HI and 0.5, 3.5 and 9.5 h after HI. MiRNA expression was measured by qRT-PCR. Results: Compared to baseline, miR-374a increased during HI (p = 0.01), remained elevated at 0.5 h after HI (p = 0.02) and was downregulated at 9.5 h after HI (p = 0.02). MiR-210 increased during HI (p = 0.02) and rapidly normalized by 0.5 h after HI. MiR-124 and miR-125b did not exhibit significant alterations. Correlations were observed between miR-374a, arterial pH, base excess and lactate levels, and between miR-210 and pO2 (p < 0.05). Conclusions: Our data suggest that miR-374a and miR-210 are important regulators in neonatal HI and might have a place as biomarkers in this setting.

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