Age increases reactive oxygen species production in macrophages and potentiates oxidative damage after spinal cord injury.
Age potentiates neurodegeneration and impairs recovery from spinal cord injury (SCI). Previously, we observed that age alters the balance of destructive (M1) and protective (M2) macrophages; however, the age-related pathophysiology in SCI is poorly understood. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) contributes to reactive oxygen species (ROS)-mediated damage and macrophage activation in neurotrauma. Further, NOX and ROS increase with central nervous system age. Here, we found significantly higher ROS generation in 14 versus 4-month-old (MO) mice after contusion SCI. Notably, NOX2 increased in 14 MO ROS-producing macrophages suggesting that macrophages and NOX contribute to SCI oxidative stress. Indicators of lipid peroxidation, a downstream cytotoxic effect of ROS accumulation, were significantly higher in 14 versus 4 MO SCI mice. We also detected a higher percentage of ROS-producing M2 (Arginase-1-positive) macrophages in 14 versus 4 MO mice, a previously unreported SCI phenotype, and increased M1 (CD16/32-positive) macrophages with age. Thus, NOX and ROS are age-related mediators of SCI pathophysiology and normally protective M2 macrophages may potentiate secondary injury through ROS generation in the aged injured spinal cord.
Spinal Cord and Brain Injury Research Center, Department of Physiology, University of Kentucky, Lexington, KY 40536, USA.
Bei
B
Zhang
Spinal Cord and Brain Injury Research Center, Department of Physiology, University of Kentucky, Lexington, KY 40536, USA.
William M
WM
Bailey
Spinal Cord and Brain Injury Research Center, Department of Physiology, University of Kentucky, Lexington, KY 40536, USA.
Anna Leigh
AL
McVicar
Spinal Cord and Brain Injury Research Center, Department of Physiology, University of Kentucky, Lexington, KY 40536, USA. Electronic address: gensel.1@uky.edu.
John C
JC
Gensel
D000375:Aging / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D004996:Ethidium / Q000031:analogs & derivatives; D005260:Female; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D008562:Membrane Glycoproteins; D008810:Mice, Inbred C57BL; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000633:toxicity; D013119:Spinal Cord Injuries / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*
D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; C067883:dihydroethidium; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D004996:Ethidium
Aging; Arginase-1; Dihydroethidium; Macrophage polarization; Microglia; gp91(phox)