Evidence map›Paper›PMID 32521540›Full record

ArticlePediatric research2021

Serial blood cytokine and chemokine mRNA and microRNA over 48 h are insult specific in a piglet model of inflammation-sensitized hypoxia-ischaemia.

Ingran Lingam, Adnan Avdic-Belltheus, Christopher Meehan, Kathryn Martinello, Sara Ragab, Donald Peebles, Melinda Barkhuizen, Cally J Tann, Ilias Tachtsidis, Tim G A M Wolfs and 7 more

Open access · bronzeAbstract readComparative Study
PubMed Publisher
In one paragraph

Article in Pediatric research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.0field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Review
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  8. Melatonin for Neonatal Encephalopathy: From Bench to Bedside.International journal of molecular sciences · 2021
    Review
  9. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 4 countries.

Ingran LingamNeonatology, Institute for Women's Health, University College London, London, UK.
Adnan Avdic-BelltheusNeonatology, Institute for Women's Health, University College London, London, UK.
Christopher MeehanNeonatology, Institute for Women's Health, University College London, London, UK.
Kathryn MartinelloNeonatology, Institute for Women's Health, University College London, London, UK.
Sara RagabNeonatology, Institute for Women's Health, University College London, London, UK.
Donald PeeblesMaternal Fetal Medicine, Institute for Women's Health, University College London, London, UK.
Melinda BarkhuizenDepartment of Pediatrics, University of Maastricht, Maastricht, The Netherlands.
Cally J TannNeonatology, Institute for Women's Health, University College London, London, UK.
Ilias TachtsidisMedical Physics and Biomedical Engineering, University College London, London, UK.
Tim G A M WolfsDepartment of Pediatrics, University of Maastricht, Maastricht, The Netherlands.
Henrik HagbergCentre of Perinatal Medicine & Health, Department of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
Nigel KleinPaediatric Infectious Diseases & Immunology, Institute of Child Health, University College London, London, UK.
Bobbi FleissCentre for the Developing Brain, Kings College London, London, UK.
Pierre GressensCentre for the Developing Brain, Kings College London, London, UK.
Xavier GolayDepartment of Brain Repair & Rehabilitation, Institute of Neurology, University College London, London, UK.
Boris W KramerMaternal Fetal Medicine, Institute for Women's Health, University College London, London, UK.
Nicola J RobertsonNeonatology, Institute for Women's Health, University College London, London, UK. n.robertson@ucl.ac.uk.
University College London · GBLondon Women's Clinic · GBMaastricht University · NLKing's College London · GBLondon School of Hygiene & Tropical Medicine · GBUniversité Paris Cité · FR

Funding

Why is the prevalence of obesity so high in U.S. Southern States? Regional predictors of BMI and obesity treatment response.P30DK056336 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BARBARA A GOWER · 2000 to 2026
$31.9M
University of Alabama at Birmingham's Diabetes Research CenterP30DK079626 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Kirk Michael Habegger · 2013 to 2026
$19.5M
Project 2: Leveraging Ongoing Home Visitation Programs to Address Obesity Disparities among Underserved, Low-Income Mothers and ChildrenU54MD000502 · NIMHD · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SALVY, SARAH-JEANNE · 2017 to 2022
$11.8M
UAB Pre-Doctoral Training Program in Obesity-Related ResearchT32HL105349 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BARBARA A GOWER · 2010 to 2026
$5.7M
Department of HealthMedical Research Council MR/M006743/1NHLBI NIH HHS T32 HL105349NIDDK NIH HHS P30 DK056336NIDDK NIH HHS P30 DK079626NIMHD NIH HHS U54 MD000502
6 · The paper itself

Abstract

backgroundExposure to inflammation exacerbates injury in neonatal encephalopathy (NE). We hypothesized that brain biomarker mRNA, cytokine mRNA and microRNA differentiate inflammation (E. coli LPS), hypoxia (Hypoxia), and inflammation-sensitized hypoxia (LPS+Hypoxia) in an NE piglet model.

methodsSixteen piglets were randomized: (i) LPS 2 μg/kg bolus; 1 μg/kg infusion (LPS; n = 5), (ii) Saline with hypoxia (Hypoxia; n = 6), (iii) LPS commencing 4 h pre-hypoxia (LPS+Hypoxia; n = 5). Total RNA was acquired at baseline, 4 h after LPS and 1, 3, 6, 12, 24, 48 h post-insult (animals euthanized at 48 h). Quantitative PCR was performed for cytokines (IL1A, IL6, CXCL8, IL10, TNFA) and brain biomarkers (ENO2, UCHL1, S100B, GFAP, CRP, BDNF, MAPT). MicroRNA was detected using GeneChip (Affymetrix) microarrays. Fold changes from baseline were compared between groups and correlated with cell death (TUNEL) at 48 h.

resultsWithin 6 h post-insult, we observed increased IL1A, CXCL8, CCL2 and ENO2 mRNA in LPS+Hypoxia and LPS compared to Hypoxia. IL10 mRNA differentiated all groups. Four microRNAs differentiated LPS+Hypoxia and Hypoxia: hsa-miR-23a, 27a, 31-5p, 193-5p. Cell death correlated with TNFA (R = 0.69; p < 0.01) at 1-3 h and ENO2 (R = -0.69; p = 0.01) at 48 h.

conclusionsmRNA and miRNA differentiated hypoxia from inflammation-sensitized hypoxia within 6 h in a piglet model. This information may inform human studies to enable triage for tailored neuroprotection in NE. IMPACT: Early stratification of infants with neonatal encephalopathy is key to providing tailored neuroprotection. IL1A, CXCL8, IL10, CCL2 and NSE mRNA are promising biomarkers of inflammation-sensitized hypoxia. IL10 mRNA levels differentiated all three pathological states; fold changes from baseline was the highest in LPS+Hypoxia animals, followed by LPS and Hypoxia at 6 h. miR-23, -27, -31-5p and -193-5p were significantly upregulated within 6 h of a hypoxia insult. Functional analysis highlighted the diverse roles of miRNA in cellular processes.

Indexed as

AnimalsAnimals, NewbornBiomarkersBrainChemokinesCytokinesDisease Models, AnimalEndotoxemiaGene Expression RegulationGene OntologyHumansHypoxia-Ischemia, BrainInflammationLipopolysaccharidesMaleMicroRNAsBiomarkersChemokinesCytokinesLipopolysaccharidesMicroRNAsNerve Tissue ProteinsPhosphopyruvate HydrataseRNA, MessengerTumor Necrosis Factor-alpha

Identifiers

PMID32521540
OpenAlexW3033311404

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.