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 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.
['Sävman|Karin|K|', 'Heyes|Melvyn P|MP|', 'Svedin|Pernilla|P|', 'Karlsson|Anna|A|']
D001238:Asphyxia Neonatorum D015415:Biomarkers D001798:Blood Proteins D004797:Enzyme-Linked Immunosorbent Assay D005260:Female D037502:Galectin 3 D037161:Galectins D008401:Gas Chromatography-Mass Spectrometry D006801:Humans D007231:Infant, Newborn D008264:Macrophages D008297:Male D017628:Microglia D011379:Prognosis D017378:Quinolinic Acid
Microglia Quinolinic acid Neonate Cerebrospinal fluid galectin-3 Hypoxic–ischemic brain injury