Frontiers in Molecular Neuroscience (Sep 2021)
Novel Point-of-Care Diagnostic Method for Neonatal Encephalopathy Using Purine Nucleosides
- Edward Beamer,
- Edward Beamer,
- Mary Isabel O’Dea,
- Mary Isabel O’Dea,
- Mary Isabel O’Dea,
- Mary Isabel O’Dea,
- Aisling A. Garvey,
- Aisling A. Garvey,
- Jonathon Smith,
- Jonathon Smith,
- Aida Menéndez-Méndez,
- Lynne Kelly,
- Lynne Kelly,
- Andreea Pavel,
- Andreea Pavel,
- Sean Quinlan,
- Mariana Alves,
- Eva M. Jimenez-Mateos,
- Faming Tian,
- Eugene Dempsey,
- Eugene Dempsey,
- Nicholas Dale,
- Deirdre M. Murray,
- Deirdre M. Murray,
- Geraldine B. Boylan,
- Geraldine B. Boylan,
- Eleanor J. Molloy,
- Eleanor J. Molloy,
- Eleanor J. Molloy,
- Eleanor J. Molloy,
- Tobias Engel,
- Tobias Engel
Affiliations
- Edward Beamer
- Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland
- Edward Beamer
- Centre for Bioscience, Manchester Metropolitan University, Manchester, United Kingdom
- Mary Isabel O’Dea
- Coombe Women and Infants University Hospital, Dublin, Ireland
- Mary Isabel O’Dea
- National Children’s Research Centre, Crumlin, Dublin, Ireland
- Mary Isabel O’Dea
- Discipline of Paediatrics, Children’s Health Ireland at Crumlin and Tallaght, Dublin, Ireland
- Mary Isabel O’Dea
- Trinity Research in Childhood Centre (TRiCC), Trinity College Dublin, The University of Dublin, Dublin, Ireland
- Aisling A. Garvey
- INFANT Research Centre, University College Cork, Dublin, Ireland
- Aisling A. Garvey
- Department of Paediatrics and Child Health, University College Cork, Dublin, Ireland
- Jonathon Smith
- Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland
- Jonathon Smith
- FutureNeuro, Science Foundation Ireland Research Centre for Chronic and Rare Neurological Diseases, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland
- Aida Menéndez-Méndez
- Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland
- Lynne Kelly
- Coombe Women and Infants University Hospital, Dublin, Ireland
- Lynne Kelly
- Discipline of Paediatrics, Children’s Health Ireland at Crumlin and Tallaght, Dublin, Ireland
- Andreea Pavel
- INFANT Research Centre, University College Cork, Dublin, Ireland
- Andreea Pavel
- Department of Paediatrics and Child Health, University College Cork, Dublin, Ireland
- Sean Quinlan
- Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland
- Mariana Alves
- Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland
- Eva M. Jimenez-Mateos
- 0Discipline of Physiology, School of Medicine, Trinity College Dublin, The University of Dublin, Dublin, Ireland
- Faming Tian
- 1School of Life Sciences, University of Warwick, Coventry, United Kingdom
- Eugene Dempsey
- INFANT Research Centre, University College Cork, Dublin, Ireland
- Eugene Dempsey
- Department of Paediatrics and Child Health, University College Cork, Dublin, Ireland
- Nicholas Dale
- 1School of Life Sciences, University of Warwick, Coventry, United Kingdom
- Deirdre M. Murray
- INFANT Research Centre, University College Cork, Dublin, Ireland
- Deirdre M. Murray
- Department of Paediatrics and Child Health, University College Cork, Dublin, Ireland
- Geraldine B. Boylan
- INFANT Research Centre, University College Cork, Dublin, Ireland
- Geraldine B. Boylan
- Department of Paediatrics and Child Health, University College Cork, Dublin, Ireland
- Eleanor J. Molloy
- Coombe Women and Infants University Hospital, Dublin, Ireland
- Eleanor J. Molloy
- National Children’s Research Centre, Crumlin, Dublin, Ireland
- Eleanor J. Molloy
- Discipline of Paediatrics, Children’s Health Ireland at Crumlin and Tallaght, Dublin, Ireland
- Eleanor J. Molloy
- Trinity Research in Childhood Centre (TRiCC), Trinity College Dublin, The University of Dublin, Dublin, Ireland
- Tobias Engel
- Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland
- Tobias Engel
- FutureNeuro, Science Foundation Ireland Research Centre for Chronic and Rare Neurological Diseases, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland
- DOI
- https://doi.org/10.3389/fnmol.2021.732199
- Journal volume & issue
-
Vol. 14
Abstract
Background: Evidence suggests that earlier diagnosis and initiation of treatment immediately after birth is critical for improved neurodevelopmental outcomes following neonatal encephalopathy (NE). Current diagnostic tests are, however, mainly restricted to clinical diagnosis with no molecular tests available. Purines including adenosine are released during brain injury such as hypoxia and are also present in biofluids. Whether blood purine changes can be used to diagnose NE has not been investigated to date.Methods: Blood purines were measured in a mouse model of neonatal hypoxia and infants with NE using a novel point-of-care diagnostic technology (SMARTChip) based on the summated electrochemical detection of adenosine and adenosine metabolites in the blood.Results: Blood purine concentrations were ∼2–3-fold elevated following hypoxia in mice [2.77 ± 0.48 μM (Control) vs. 7.57 ± 1.41 μM (post-hypoxia), p = 0.029]. Data in infants with NE had a 2–3-fold elevation when compared to healthy controls [1.63 ± 0.47 μM (Control, N = 5) vs. 4.87 ± 0.92 μM (NE, N = 21), p = 0.0155]. ROC curve analysis demonstrates a high sensitivity (81%) and specificity (80%) for our approach to identify infants with NE. Moreover, blood purine concentrations were higher in infants with NE and seizures [8.13 ± 3.23 μM (with seizures, N = 5) vs. 3.86 ± 0.56 μM (without seizures, N = 16), p = 0.044].Conclusion: Our data provides the proof-of-concept that measurement of blood purine concentrations via SMARTChip technology may offer a low-volume bedside test to support a rapid diagnosis of NE.
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