BM-derived cells are recruited in a CCR2-dependent manner into demyelinating sites of the CNS in the cuprizone model. (A) A Busulfan/Cyclophosphamide chemotherapy regimen was used to prepare WT mice to receive the injection of BM cells from GFP^+/− mice. 6 wk after transplantation, 0.2% Cuprizone was added to the diet for up to 6 wk. Mice were sacrificed after 2, 3, 4, 5, and 6 wk on a cuprizone-supplemented diet. Another group was sacrificed 2 wk after removing cuprizone from the diet to allow remyelination. (B) Flow cytometry analysis of GFP expression in circulating monocytes of WT mice, GFP^+/− mice, chimeric GFP → WT mice, and and CCR2^−/− → WT mice. (C) GFP⁺ cells were counted with a stereologic apparatus. Reported is the total number of GFP⁺ cells per slice counted per animal. (D-F) Representative confocal images of GFP⁺ cells (green) and immunoreactive Iba1⁺ cells (red) in the hippocampus and corpus callosum of chimeric mice either untreated (D) or after 5 wk of treatment with a cuprizone diet in GFP (E) and CCR2^−/− (F) chimeric mice. One representative experiment out of two is shown. n = 3–9 mice/group. ****, P < 0.0001. Bars, 100 µm.