naa a22 4500 510776272 CHVBK 20180411083231.0 cr unu---uuuuu 180411e20130401xx s 000 0 eng 10.1007/s12975-012-0216-3 doi (NATIONALLICENCE)springer-10.1007/s12975-012-0216-3 Microglia/Macrophage-Derived Inflammatory Mediators Galectin-3 and Quinolinic Acid are Elevated in Cerebrospinal Fluid from Newborn Infants After Birth Asphyxia [Elektronische Daten] [Karin Sävman, Melvyn Heyes, Pernilla Svedin, Anna Karlsson] 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 Science+Business Media New York, 2012 Hypoxic-ischemic brain injury nationallicence Microglia nationallicence Neonate nationallicence Cerebrospinal fluid galectin-3 nationallicence Quinolinic acid nationallicence Sävman Karin Perinatal Center, Department of Pediatrics, Sahlgrenska Academy, University of Gothenburg, 416 85, Göteborg, Sweden aut Heyes Melvyn Laboratory of Neurotoxicology, National Institute of Mental Health, 20892, Bethesda, MD, USA aut Svedin Pernilla Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 416 85, Göteborg, Sweden aut Karlsson Anna Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 46, Göteborg, Sweden aut Translational Stroke Research Springer-Verlag 4/2(2013-04-01), 228-235 1868-4483 4:2<228 2013 4 12975 https://doi.org/10.1007/s12975-012-0216-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12975-012-0216-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sävman Karin Perinatal Center, Department of Pediatrics, Sahlgrenska Academy, University of Gothenburg, 416 85, Göteborg, Sweden aut NATIONALLICENCE 700 1- Heyes Melvyn Laboratory of Neurotoxicology, National Institute of Mental Health, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Svedin Pernilla Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 416 85, Göteborg, Sweden aut NATIONALLICENCE 700 1- Karlsson Anna Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 46, Göteborg, Sweden aut NATIONALLICENCE 773 0- Translational Stroke Research Springer-Verlag 4/2(2013-04-01), 228-235 1868-4483 4:2<228 2013 4 12975 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer