Age increases reactive oxygen species production in macrophages and potentiates oxidative damage after spinal cord injury

Bei Zhang, William M. Bailey, Anna Leigh McVicar, John C. Gensel

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


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.

Original languageEnglish
Pages (from-to)157-167
Number of pages11
JournalNeurobiology of Aging
StatePublished - Nov 1 2016

Bibliographical note

Funding Information:
The authors would like to thank Dr Edward Hall, Dr Indrapal Singh, and Linda Simmerman for technical support and advice. The current work was supported by the Craig H. Neilsen Foundation and by the National Institute of Neurological Disorders with grants R01 NS091582 and P30 NS051220 .

Publisher Copyright:
© 2016 Elsevier Inc.


  • Aging
  • Arginase-1
  • Dihydroethidium
  • Macrophage polarization
  • Microglia
  • gp91

ASJC Scopus subject areas

  • Neuroscience (all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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