The OP population dynamics were dramatically different in response to acute versus chronic demyelination (Fig. 3) . In response to the initial episode of acute demyelination, the OP population was amplified almost fourfold (Fig. 3) . However, by the end of the chronic demyelination period, the OP density was greatly reduced and remained low during the recovery period. In the chronic lesions, similar results were observed with OP identification using PDGF>R (Fig. 3A ) and using NG2 (12 weeks cuprizone = 155 cells/mm 2 , n = 5; 12 weeks cuprizone plus 3 weeks recovery Figure 1 ) of corpus callosum myelination estimated by immunostaining for myelin oligodendrocyte glycoprotein (MOG) in cuprizone-treated FGF2 j/j mice (A) and FGF2 +/+ mice (B). The corpus callosum showed persistent demyelination with 0.2% cuprizone ingestion throughout 9 weeks and 12 weeks. After 12 weeks of cuprizone treatment, on return to normal chow, remyelination in FGF2 j/j mice significantly improved (p G 0.001; 12 weeks cuprizone, n = 4; 12 weeks cuprizone 6 weeks off, n = 4) and recovered to nonlesioned levels (p > 0.05; no cuprizone, n = 5; 12 weeks cuprizone 6 weeks off). In contrast, values in FGF2 +/+ mice did not increase after chronic demyelination (p > 0.05; 12 weeks cuprizone, n = 4 vs. 12 weeks cuprizone 6 weeks off, n = 3) and remained significantly below nonlesioned levels (p G 0.001; no cuprizone, n = 5 vs. 12 weeks cup). = 169 cells/mm 2 , n = 6; 12 weeks cuprizone plus 6 weeks recovery = 115 cells/mm 2 , n = 5). At 12 weeks of cuprizone treatment, very few cells in the corpus callosum were identified as actively undergoing mitosis using DAPI counterstaining to reveal mitotic chromatin figures, but each actively dividing cell was also immunostained for NG2 (inset, Fig. 3A ). Immunostaining for Ki-67 nuclear antigen was used to more broadly identify actively cycling cells within the corpus callosum (Fig. 3B) . Ki-67-labeled cycling cells were present at less than half the density of OP cells. This cycling population, although still relatively small, was significantly increased within the corpus callosum of mice fed cuprizone for 12 weeks as compared with age-matched controls or with mice that had recovered for 6 weeks after chronic demyelination. Together, these findings demonstrated compromised but continued OP cycling and regeneration of oligodendrocytes during chronic demyelination and the subsequent recovery period (Figs. 2, 3 ).