Oxidative burst of circulating neutrophils following traumatic brain injury in human

PLoS One. 2013 Jul 24;8(7):e68963. doi: 10.1371/journal.pone.0068963. Print 2013.


Besides secondary injury at the lesional site, Traumatic brain injury (TBI) can cause a systemic inflammatory response, which may cause damage to initially unaffected organs and potentially further exacerbate the original injury. Here we investigated plasma levels of important inflammatory mediators, oxidative activity of circulating leukocytes, particularly focusing on neutrophils, from TBI subjects and control subjects with general trauma from 6 hours to 2 weeks following injury, comparing with values from uninjured subjects. We observed increased plasma level of inflammatory cytokines/molecules TNF-α, IL-6 and CRP, dramatically increased circulating leukocyte counts and elevated expression of TNF-α and iNOS in circulating leukocytes from TBI patients, which suggests a systemic inflammatory response following TBI. Our data further showed increased free radical production in leukocyte homogenates and elevated expression of key oxidative enzymes iNOS, COX-2 and NADPH oxidase (gp91(phox)) in circulating leukocytes, indicating an intense induction of oxidative burst following TBI, which is significantly greater than that in control subjects with general trauma. Furthermore, flow cytometry assay proved neutrophils as the largest population in circulation after TBI and showed significantly up-regulated oxidative activity and suppressed phagocytosis rate for circulating neutrophils following brain trauma. It suggests that the highly activated neutrophils might play an important role in the secondary damage, even outside the injured brain. Taken together, the potent systemic inflammatory response induced by TBI, especially the intensively increase oxidative activity of circulating leukocytes, mainly neutrophils, may lead to a systemic damage, dysfunction/damage of bystander tissues/organs and even further exacerbate secondary local damage. Controlling these pathophysiological processes may be a promising therapeutic strategy and will protect unaffected organs and the injured brain from the secondary damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain Injuries / blood
  • Brain Injuries / immunology*
  • C-Reactive Protein / metabolism
  • Cyclooxygenase 2 / metabolism
  • Female
  • Humans
  • Interleukin-6 / blood
  • Interleukin-6 / metabolism
  • Leukocytes / metabolism
  • Leukocytes / physiology
  • Male
  • Middle Aged
  • NADPH Oxidases / metabolism
  • Neutrophils / metabolism
  • Neutrophils / physiology*
  • Nitric Oxide Synthase Type II / metabolism
  • Phagocytosis / physiology
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / metabolism


  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • NADPH Oxidases

Grant support

The present study was partially supported by two project fundings as following: Natural Science Foundation of China (http://www.nsfc.gov.cn/e_nsfc/desktop/zn/0101.htm), Project of CQ CSTC (No. 2010BB5025); and State Science and Technology Major Projects of New Drugs (http://www.nmp.gov.cn/) (No. 2012ZX09103301-035). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.