To better evaluate the underlying causes of limited remyelination after chronic demyelination, we characterized the oligodendrocyte lineage cell responses relative to disease progression with a focus on the repair potential. Oligodendrocyte and OP populations were characterized during multiple stages of disease progression: nonlesioned (no cuprizone), acute demyelination (3Y5 weeks of continuous cuprizone), chronic demyelination (12 weeks of continuous cuprizone), and recovery after chronic demyelination (12 weeks of continuous cuprizone followed by normal chow for 3 or 6 weeks). In situ hybridization was used to identify oligodendrocytes expressing PLP mRNA transcripts (Fig. 2) and OP cells expressing FIGURE 2 . Oligodendroglial repopulation of the corpus callosum was compromised after chronic demyelination of C57Bl/6 mice. (A) Quantification of the density of oligodendrocytes in the corpus callosum of C57Bl/6 mice. In situ hybridization for PLP mRNA, which identifies premyelinating and myelinating oligodendrocytes, was quantified using unbiased stereology with at least three sections per mouse and at least four mice per condition. Bar colors indicate no cuprizone (white), acute cuprizone (gray), or chronic cuprizone (black). The oligodendrocyte density after 12 weeks of cuprizone followed by 6 weeks for recovery was still significantly below nonlesioned values (p > 0.05; n = 5 for both conditions). Significant differences, p G 0.05 or less, are noted by an asterisk (*) for comparisons with no cuprizone and with a carrot (^) for comparisons of recovery stages with 12 week cuprizone. platelet-derived growth factor > receptor (PDGF>R) mRNA transcripts (Fig. 3) .