Traumatic brain injury induces macrophage subsets in the brain

Eur J Immunol. 2013 Aug;43(8):2010-22. doi: 10.1002/eji.201243084. Epub 2013 Jun 5.


Traumatic brain injury (TBI) elicits innate inflammatory responses that can lead to secondary brain injury. To better understand the mechanisms involved in TBI-induced inflammation, we examined the nature of macrophages responding to TBI in mice. In this model, brain macrophages were increased >20-fold the day after injury and >77-fold 4 days after injury in the ipsilateral hemisphere compared with sham controls. TBI macrophage subsets were identified by using a reporter mouse strain (YARG) that expresses eYFP from an internal ribosome entry site (IRES) inserted at the 3' end of the gene for arginase-1 (Arg1), a hallmark of alternatively activated (M2) macrophages. One day after TBI, 21 ± 1.5% of ipsilateral brain macrophages expressed relatively high levels of Arg1 as detected by yellow fluorescent protein, and this subpopulation declined thereafter. Arg1(+) cells localized with macrophages near the TBI lesion. Gene expression analysis of sorted Arg1(+) and Arg1(-) brain macrophages revealed that both populations had profiles that included features of conventional M2 macrophages and classically activated (M1) macrophages. The Arg1(+) cells differed from Arg1(-) cells in multiple aspects, most notably in their chemokine repertoires. Thus, the macrophage response to TBI initially involves heterogeneous polarization toward at least two major subsets.

Keywords: Alternative activation; Inflammation; Macrophage; Traumatic brain injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Arginase / genetics
  • Arginase / metabolism*
  • Bacterial Proteins / genetics
  • Brain / immunology*
  • Brain Injuries / immunology*
  • Cell Movement
  • Chemokines / biosynthesis
  • Gene Expression Profiling
  • Inflammation / immunology
  • Luminescent Proteins / genetics
  • Macrophage Activation / immunology*
  • Macrophages / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Ribosomes / genetics
  • Ribosomes / metabolism


  • Bacterial Proteins
  • Chemokines
  • Luminescent Proteins
  • yellow fluorescent protein, Bacteria
  • Arg1 protein, mouse
  • Arginase

Associated data

  • GEO/GSE39759