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Microglia/Macrophage-Derived Inflammatory Mediators Galectin-3 and Quinolinic Acid are Elevated in Cerebrospinal Fluid from Newborn Infants After Birth Asphyxia
Activation of microglia/macrophages is important in neonatal hypoxic–ischemic (HI) brain injury. Based on experimental studies, we identified macrophage/microglia-derived mediators with potential neurotoxic effects after neonatal HI and examined them in cerebrospinal fluid (CSF) from newborn infants...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer-Verlag
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685715/ https://www.ncbi.nlm.nih.gov/pubmed/23807898 http://dx.doi.org/10.1007/s12975-012-0216-3 |
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author | Sävman, Karin Heyes, Melvyn P. Svedin, Pernilla Karlsson, Anna |
author_facet | Sävman, Karin Heyes, Melvyn P. Svedin, Pernilla Karlsson, Anna |
author_sort | Sävman, Karin |
collection | PubMed |
description | Activation of microglia/macrophages is important in neonatal hypoxic–ischemic (HI) brain injury. Based on experimental studies, we identified macrophage/microglia-derived mediators with potential neurotoxic effects after neonatal HI and examined them in cerebrospinal fluid (CSF) from newborn infants after birth asphyxia. Galectin-3 is a novel inflammatory mediator produced by microglia/macrophages. Galectin-3 is chemotactic for inflammatory cells and activates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase resulting in production and release of reactive oxygen species (ROS). Matrix metalloproteinase-9 (MMP-9) is a tissue-degrading protease expressed by activated microglia in the immature brain after HI. Both galectin-3 and MMP-9 contribute to brain injury in animal models for neonatal HI. Quinolinic acid (QUIN) is a neurotoxic N-methyl-d-aspartate (NMDA) receptor agonist also produced by activated microglia/macrophages. Galectin-3 and MMP-9 were measured by ELISA and QUIN by mass spectrometry. Asphyxiated infants (n = 20) had higher levels of galectin-3 (mean (SEM) 2.64 (0.43) ng/mL) and QUIN (335.42 (58.9) nM) than controls (n = 15) (1.36 (0.46) ng/mL and 116.56 (16.46) nM, respectively), p < 0.05 and p < 0.01. Infants with septic infections (n = 10) did not differ from controls. Asphyxiated infants with abnormal outcome had higher levels of galectin-3 (3.96 (0.67) ng/mL) than those with normal outcome (1.76 (0.32) ng/mL), p = 0.02, and the difference remained significant in the clinically relevant group of infants with moderate encephalopathy. MMP-9 was detected in few infants with no difference between groups. The potentially neurotoxic macrophage/microglia-derived mediators galectin-3 and QUIN are increased in CSF after birth asphyxia and could serve as markers and may contribute to injury. |
format | Online Article Text |
id | pubmed-3685715 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Springer-Verlag |
record_format | MEDLINE/PubMed |
spelling | pubmed-36857152013-06-25 Microglia/Macrophage-Derived Inflammatory Mediators Galectin-3 and Quinolinic Acid are Elevated in Cerebrospinal Fluid from Newborn Infants After Birth Asphyxia Sävman, Karin Heyes, Melvyn P. Svedin, Pernilla Karlsson, Anna Transl Stroke Res Original Article Activation of microglia/macrophages is important in neonatal hypoxic–ischemic (HI) brain injury. Based on experimental studies, we identified macrophage/microglia-derived mediators with potential neurotoxic effects after neonatal HI and examined them in cerebrospinal fluid (CSF) from newborn infants after birth asphyxia. Galectin-3 is a novel inflammatory mediator produced by microglia/macrophages. Galectin-3 is chemotactic for inflammatory cells and activates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase resulting in production and release of reactive oxygen species (ROS). Matrix metalloproteinase-9 (MMP-9) is a tissue-degrading protease expressed by activated microglia in the immature brain after HI. Both galectin-3 and MMP-9 contribute to brain injury in animal models for neonatal HI. Quinolinic acid (QUIN) is a neurotoxic N-methyl-d-aspartate (NMDA) receptor agonist also produced by activated microglia/macrophages. Galectin-3 and MMP-9 were measured by ELISA and QUIN by mass spectrometry. Asphyxiated infants (n = 20) had higher levels of galectin-3 (mean (SEM) 2.64 (0.43) ng/mL) and QUIN (335.42 (58.9) nM) than controls (n = 15) (1.36 (0.46) ng/mL and 116.56 (16.46) nM, respectively), p < 0.05 and p < 0.01. Infants with septic infections (n = 10) did not differ from controls. Asphyxiated infants with abnormal outcome had higher levels of galectin-3 (3.96 (0.67) ng/mL) than those with normal outcome (1.76 (0.32) ng/mL), p = 0.02, and the difference remained significant in the clinically relevant group of infants with moderate encephalopathy. MMP-9 was detected in few infants with no difference between groups. The potentially neurotoxic macrophage/microglia-derived mediators galectin-3 and QUIN are increased in CSF after birth asphyxia and could serve as markers and may contribute to injury. Springer-Verlag 2012-10-13 2013-04 /pmc/articles/PMC3685715/ /pubmed/23807898 http://dx.doi.org/10.1007/s12975-012-0216-3 Text en © Springer Science+Business Media New York 2012 |
spellingShingle | Original Article Sävman, Karin Heyes, Melvyn P. Svedin, Pernilla Karlsson, Anna Microglia/Macrophage-Derived Inflammatory Mediators Galectin-3 and Quinolinic Acid are Elevated in Cerebrospinal Fluid from Newborn Infants After Birth Asphyxia |
title | Microglia/Macrophage-Derived Inflammatory Mediators Galectin-3 and Quinolinic Acid are Elevated in Cerebrospinal Fluid from Newborn Infants After Birth Asphyxia |
title_full | Microglia/Macrophage-Derived Inflammatory Mediators Galectin-3 and Quinolinic Acid are Elevated in Cerebrospinal Fluid from Newborn Infants After Birth Asphyxia |
title_fullStr | Microglia/Macrophage-Derived Inflammatory Mediators Galectin-3 and Quinolinic Acid are Elevated in Cerebrospinal Fluid from Newborn Infants After Birth Asphyxia |
title_full_unstemmed | Microglia/Macrophage-Derived Inflammatory Mediators Galectin-3 and Quinolinic Acid are Elevated in Cerebrospinal Fluid from Newborn Infants After Birth Asphyxia |
title_short | Microglia/Macrophage-Derived Inflammatory Mediators Galectin-3 and Quinolinic Acid are Elevated in Cerebrospinal Fluid from Newborn Infants After Birth Asphyxia |
title_sort | microglia/macrophage-derived inflammatory mediators galectin-3 and quinolinic acid are elevated in cerebrospinal fluid from newborn infants after birth asphyxia |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685715/ https://www.ncbi.nlm.nih.gov/pubmed/23807898 http://dx.doi.org/10.1007/s12975-012-0216-3 |
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