Figure 7.

PI-88 acts via heparanase inhibition to rescue IFN-γ-mediated quiescence of OPCs. A, B, Control (A) and IFN-γ (B) mouse groups underwent focal spinal cord demyelination with or without PI-88 or OGT2115 injection and were killed at 5 dpl. Immunofluorescence for Olig2 (green) and EdU (red) was performed. C, D, OPC recruitment (Olig2⁺ cells/mm²; C) and proliferation (EdU percentage among Olig2⁺ cells; D) were quantified. Both PI-88 and OGT2115 treatment rescued the negative effects of IFN-γ on OPC recruitment (G) and proliferation (H) following demyelination (mean ± SEM; n = 3–4 mice/group). Two-way ANOVA interaction for Olig2⁺ cell density and percentage EdU OPCs were Holm–Sidak test: *p < 0.05, **p < 0.01 (Extended Data Fig. 7-1). Red and green denotes p value compared to matched untreated controls. E, F, at 0.5 h following treatment with or without PI-88 (2 μg/ml) or OGT2155 (0.4 μM) hOPCs were treated with vehicle (E) or IFN-γ (F) (10 ng/ml). O4⁺ oligodendrocyte (red) differentiation was assessed at 48 h and the proportion of O4⁺ cells quantified (mean ± SEM, n = 3 fetal samples) following PI-88 (G) or OGT2155 (H). IFN-γ has a significant inhibitory effect of differentiation (red, *), which is rescued by PI-88 (two-way ANOVA; Extended Data Fig. 7-2) but not OGT2115 treatment (two-way ANOVA; Extended Data Fig. 7-3). Holm–Sidak test: *p < 0.05 following two-way ANOVA. Scale bars: A, B, 20 µm; E, F, 50 µm. ns denotes not significant. ***p < 0.001, ****p < 0.0001.