Umbilical Cord Blood NOS1 as a Potential Biomarker of Neonatal Encephalopathy

BackgroundThere are no definitive markers to aid in diagnosis of neonatal encephalopathy (NE). The purpose of our study was (1) to identify and evaluate the utility of neuronal nitric oxide synthase (NOS1) in umbilical cord blood as a NE biomarker and (2) to identify the source of NOS1 in umbilical...

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Main Authors: Jun Lei, Cristina Paules, Elisabeth Nigrini, Jason M. Rosenzweig, Rudhab Bahabry, Azadeh Farzin, Samuel Yang, Frances J. Northington, Daniel Oros, Stephanie McKenney, Michael V. Johnston, Ernest M. Graham, Irina Burd
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-05-01
Series:Frontiers in Pediatrics
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fped.2017.00112/full
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author Jun Lei
Cristina Paules
Elisabeth Nigrini
Jason M. Rosenzweig
Rudhab Bahabry
Azadeh Farzin
Samuel Yang
Frances J. Northington
Frances J. Northington
Frances J. Northington
Daniel Oros
Stephanie McKenney
Michael V. Johnston
Michael V. Johnston
Michael V. Johnston
Ernest M. Graham
Ernest M. Graham
Irina Burd
Irina Burd
Irina Burd
Irina Burd
spellingShingle Jun Lei
Cristina Paules
Elisabeth Nigrini
Jason M. Rosenzweig
Rudhab Bahabry
Azadeh Farzin
Samuel Yang
Frances J. Northington
Frances J. Northington
Frances J. Northington
Daniel Oros
Stephanie McKenney
Michael V. Johnston
Michael V. Johnston
Michael V. Johnston
Ernest M. Graham
Ernest M. Graham
Irina Burd
Irina Burd
Irina Burd
Irina Burd
Umbilical Cord Blood NOS1 as a Potential Biomarker of Neonatal Encephalopathy
Frontiers in Pediatrics
neonatal encephalopathy
biomarkers
umbilical veins
NOS1
diagnosis
author_facet Jun Lei
Cristina Paules
Elisabeth Nigrini
Jason M. Rosenzweig
Rudhab Bahabry
Azadeh Farzin
Samuel Yang
Frances J. Northington
Frances J. Northington
Frances J. Northington
Daniel Oros
Stephanie McKenney
Michael V. Johnston
Michael V. Johnston
Michael V. Johnston
Ernest M. Graham
Ernest M. Graham
Irina Burd
Irina Burd
Irina Burd
Irina Burd
author_sort Jun Lei
title Umbilical Cord Blood NOS1 as a Potential Biomarker of Neonatal Encephalopathy
title_short Umbilical Cord Blood NOS1 as a Potential Biomarker of Neonatal Encephalopathy
title_full Umbilical Cord Blood NOS1 as a Potential Biomarker of Neonatal Encephalopathy
title_fullStr Umbilical Cord Blood NOS1 as a Potential Biomarker of Neonatal Encephalopathy
title_full_unstemmed Umbilical Cord Blood NOS1 as a Potential Biomarker of Neonatal Encephalopathy
title_sort umbilical cord blood nos1 as a potential biomarker of neonatal encephalopathy
publisher Frontiers Media S.A.
series Frontiers in Pediatrics
issn 2296-2360
publishDate 2017-05-01
description BackgroundThere are no definitive markers to aid in diagnosis of neonatal encephalopathy (NE). The purpose of our study was (1) to identify and evaluate the utility of neuronal nitric oxide synthase (NOS1) in umbilical cord blood as a NE biomarker and (2) to identify the source of NOS1 in umbilical cord blood.MethodsThis was a nested case–control study of neonates >35 weeks of gestation. ELISA for NOS1 in umbilical cord blood was performed. Sources of NOS1 in umbilical cord were investigated by immunohistochemistry, western blot, ELISA, and quantitative PCR. Furthermore, umbilical cords of full-term neonates were subjected to 1% hypoxia ex vivo.ResultsNOS1 was present in umbilical cord blood and increased in NE cases compared with controls. NOS1 was expressed in endothelial cells of the umbilical cord vein, but not in artery or blood cells. In ex vivo experiments, hypoxia was associated with increased levels of NOS1 in venous endothelial cells of the umbilical cord as well as in ex vivo culture medium.ConclusionThis is the first study to investigate an early marker of NE. NOS1 is elevated with hypoxia, and further studies are needed to investigate it as a valuable tool for early diagnosis of neonatal brain injury.
topic neonatal encephalopathy
biomarkers
umbilical veins
NOS1
diagnosis
url http://journal.frontiersin.org/article/10.3389/fped.2017.00112/full
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spelling doaj-7eb32b83f64b4dedb59a61717c39cb4a2020-11-24T21:05:59ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602017-05-01510.3389/fped.2017.00112246929Umbilical Cord Blood NOS1 as a Potential Biomarker of Neonatal EncephalopathyJun Lei0Cristina Paules1Elisabeth Nigrini2Jason M. Rosenzweig3Rudhab Bahabry4Azadeh Farzin5Samuel Yang6Frances J. Northington7Frances J. Northington8Frances J. Northington9Daniel Oros10Stephanie McKenney11Michael V. Johnston12Michael V. Johnston13Michael V. Johnston14Ernest M. Graham15Ernest M. Graham16Irina Burd17Irina Burd18Irina Burd19Irina Burd20Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USAAragón Health Research Institute, SAMID Network ref RD12/0026/001, Zaragoza, SpainIntegrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USAIntegrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USAIntegrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USAIntegrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USANeurosciences Intensive Care Nursery Program, Johns Hopkins University School of Medicine, Baltimore, MD, USAAragón Health Research Institute, SAMID Network ref RD12/0026/001, Zaragoza, SpainIntegrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USANeurosciences Intensive Care Nursery Program, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Neurosciences, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USAIntegrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USANeurosciences Intensive Care Nursery Program, Johns Hopkins University School of Medicine, Baltimore, MD, USAIntegrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USANeurosciences Intensive Care Nursery Program, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Neurosciences, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USABackgroundThere are no definitive markers to aid in diagnosis of neonatal encephalopathy (NE). The purpose of our study was (1) to identify and evaluate the utility of neuronal nitric oxide synthase (NOS1) in umbilical cord blood as a NE biomarker and (2) to identify the source of NOS1 in umbilical cord blood.MethodsThis was a nested case–control study of neonates >35 weeks of gestation. ELISA for NOS1 in umbilical cord blood was performed. Sources of NOS1 in umbilical cord were investigated by immunohistochemistry, western blot, ELISA, and quantitative PCR. Furthermore, umbilical cords of full-term neonates were subjected to 1% hypoxia ex vivo.ResultsNOS1 was present in umbilical cord blood and increased in NE cases compared with controls. NOS1 was expressed in endothelial cells of the umbilical cord vein, but not in artery or blood cells. In ex vivo experiments, hypoxia was associated with increased levels of NOS1 in venous endothelial cells of the umbilical cord as well as in ex vivo culture medium.ConclusionThis is the first study to investigate an early marker of NE. NOS1 is elevated with hypoxia, and further studies are needed to investigate it as a valuable tool for early diagnosis of neonatal brain injury.http://journal.frontiersin.org/article/10.3389/fped.2017.00112/fullneonatal encephalopathybiomarkersumbilical veinsNOS1diagnosis