Peripheral macrophage recruitment in cuprizone-induced CNS demyelination despite an intact blood-brain barrier

J Neuroimmunol. 2002 Sep;130(1-2):32-45. doi: 10.1016/s0165-5728(02)00205-9.


The contribution of peripheral macrophage was assessed in cuprizone intoxication, a model of demyelination and remyelination in which the blood-brain barrier remains intact. Flow cytometry of brain cells isolated from cuprizone-treated mice revealed an increase in the percentage of Mac-1(+)/CD45(hi) peripheral macrophage. To confirm these results in situ, C57BL/6 mice were lethally irradiated, transplanted with bone marrow from GFP-transgenic mice, and exposed to cuprizone. GFP(+) peripheral macrophages were seen in the CNS after 2 weeks of treatment, and infiltration continued through 6 weeks. While the peripheral macrophages were far outnumbered by the resident microglia, their recruitment across the blood-brain barrier alludes to a potentially important role.

Publication types

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

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / immunology*
  • Bone Marrow Cells / immunology
  • Bone Marrow Transplantation
  • CD3 Complex / immunology
  • Central Nervous System / cytology
  • Central Nervous System / immunology*
  • Chemotaxis, Leukocyte / drug effects
  • Chemotaxis, Leukocyte / immunology*
  • Demyelinating Autoimmune Diseases, CNS / chemically induced
  • Demyelinating Autoimmune Diseases, CNS / immunology*
  • Demyelinating Autoimmune Diseases, CNS / physiopathology
  • Disease Models, Animal
  • Flow Cytometry
  • Leukocyte Common Antigens / immunology
  • Macrophage-1 Antigen / immunology
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Radiation Chimera


  • CD3 Complex
  • Macrophage-1 Antigen
  • Leukocyte Common Antigens