title: Temporal Profile of Circulating microRNAs after Global Hypoxia-Ischemia in Newborn Piglets.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Division of Pediatric and Adolescent Medicine, Department of Pediatric Research, Oslo University Hospital, Rikshospitalet, Norway.
authors.forename: Håvard Tetlie
authors.initials: HT
authors.lastname: Garberg
authors.forename: Marianne U
authors.initials: MU
authors.lastname: Huun
authors.forename: Lars O
authors.initials: LO
authors.lastname: Baumbusch
authors.forename: Monica
authors.initials: M
authors.lastname: Åsegg-Atneosen
authors.forename: Rønnaug
authors.initials: R
authors.lastname: Solberg
authors.forename: Ola Didrik
authors.initials: OD
authors.lastname: Saugstad
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000097:blood; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000097:blood*; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D010100:Oxygen / Q000008:administration & dosage; D011897:Random Allocation; D013552:Swine; D013997:Time Factors
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D010100:Oxygen