Role of CX3CR1 (fractalkine receptor) in brain damage and inflammation induced by focal cerebral ischemia in mouse

J Cereb Blood Flow Metab. 2008 Oct;28(10):1707-21. doi: 10.1038/jcbfm.2008.64. Epub 2008 Jun 25.


CX3CR1 (fractalkine receptor) is important for sustaining normal microglial activity in the brain. Lack of CX3CR1 reportedly results in neurotoxic microglial phenotype in disease models. The objective of this study was to test the hypothesis that the absence of CX3CR1 worsens the outcome in cerebral ischemia. We observed significantly smaller (56%) infarcts and blood-brain barrier damage in CX3CR1-deficient (CX3CR1-/-) animals compared with CX3CR1+/- and wild-type mice after transient occlusion of the middle cerebral artery (MCAo). Functional recovery of CX3CR1-/- animals was enhanced, while less number of apoptotic cells and infiltrating leukocytes were found in the ipsilateral hemisphere. Expression of IL-1beta mRNA, protein, and interleukin (IL)-1Ra and tumor necrosis factor (TNF)-alpha mRNAs was lower in CX3CR1-/- mice, whereas no difference was observed in the number of IL-1beta-expressing microglia or plasma IL-1beta concentration. We observed early IL-1beta expression in astrocytes in vivo after MCAo and after oxygen-glucose deprivation in vitro, which might contribute to the ischemic damage. Our findings indicate that lack of CX3CR1 does not result in microglial neurotoxicity after MCAo, but rather significantly reduces ischemic damage and inflammation. Reduced IL-1beta and TNFalpha expression as well as decreased leukocyte infiltration might be involved in the development of smaller infarcts in CX3CR1-/- animals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Astrocytes / immunology
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Blood-Brain Barrier / pathology
  • CX3C Chemokine Receptor 1
  • Cells, Cultured
  • Encephalitis / pathology
  • Encephalitis / physiopathology*
  • Green Fluorescent Proteins / genetics
  • Infarction, Middle Cerebral Artery / immunology
  • Infarction, Middle Cerebral Artery / pathology
  • Infarction, Middle Cerebral Artery / physiopathology
  • Interleukin-1beta / blood
  • Interleukin-1beta / genetics
  • Ischemic Attack, Transient / immunology*
  • Ischemic Attack, Transient / pathology
  • Ischemic Attack, Transient / physiopathology*
  • Leukocyte Common Antigens / metabolism
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Leukocytes / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microglia / immunology
  • Microglia / metabolism
  • Microglia / pathology
  • Neurons / pathology
  • Receptors, Chemokine / genetics*
  • Receptors, Chemokine / immunology*
  • Recovery of Function / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / genetics


  • CX3C Chemokine Receptor 1
  • Cx3cr1 protein, mouse
  • Interleukin-1beta
  • Receptors, Chemokine
  • Tumor Necrosis Factor-alpha
  • Green Fluorescent Proteins
  • Leukocyte Common Antigens
  • Ptprc protein, mouse