Microglia/macrophage-derived inflammatory mediators galectin-3 and quinolinic acid are elevated in cerebrospinal fluid from newborn infants after birth asphyxia.

Abstract

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.

• Authors: Karin Sävman, Melvyn P Heyes, Pernilla Svedin, Anna Karlsson
• Journal: Translational stroke research (Transl Stroke Res) Vol. 4 Issue 2 Pg. 228-35 (Apr 2013) ISSN: 1868-601X [Electronic] United States
• PMID: 23807898 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Blood Proteins
• Galectin 3
• Galectins
• LGALS3 protein, human
• Quinolinic Acid

Topics

• Asphyxia Neonatorum (cerebrospinal fluid)
• Biomarkers (cerebrospinal fluid)
• Blood Proteins
• Enzyme-Linked Immunosorbent Assay
• Female
• Galectin 3 (cerebrospinal fluid)
• Galectins
• Gas Chromatography-Mass Spectrometry
• Humans
• Infant, Newborn
• Macrophages (metabolism)
• Male
• Microglia (metabolism)
• Prognosis
• Quinolinic Acid (cerebrospinal fluid)