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

Neonatology. 2017;111(2):133-139. doi: 10.1159/000449032. Epub 2016 Oct 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biomarkers / blood
  • Female
  • Hypoxia-Ischemia, Brain / blood*
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Oxygen / administration & dosage
  • Random Allocation
  • Swine
  • Time Factors

Substances

  • Biomarkers
  • MicroRNAs
  • Oxygen