Fig. 7: Sulfatase inhibitor PI-88 promotes OPC differentiation and remyelination following demyelination.

PI-88 was injected into demyelinated lesions in adult mouse spinal cord at the time of lysolecithin injection. a, b Olig2⁺ recruitment and proliferation (EdU⁺Olig2⁺) was assess at 5 days post lesion (d.p.l.) by widefield epifluorescence (Olig2, green; EdU, red). c–j Oligodendrocyte lineage density (Olig2, green), differentiation (Plp1 and CC1, red), and the microglial/astrocyte response was assessed at 7 d.p.l. (Gfap, green; Iba1, red). Oligodendrocyte density and differentiation were assessed by Plp1 in situ (c, d), and Olig2/CC1 immunofluorescence (e, f). g–j Astrocyte and microglial responses were assessed by Gfap and Iba1, respectively, and image inserts show higher magnification image to show morphology. k, l quantification of Olig2⁺ density (** indicates two-tailed t test p = 0.0079) and percentage of EdU⁺ cells among total Olig2 at 5 d.p.l. (n = 6 control, n = 4 for PI-88-treated mice). m–o At 7 d.p.l. quantification of Plp1⁺ cell density (m) (** indicates two-tailed t test p = 0.0048, n = 4 mice per group), Olig2⁺ and CC1⁺Olig2⁺ cell density (n) (* indicates total Olig2⁺ two-tailed t test p = 0.037), and percentage of CC1⁺ cells within the Olig2 population (o) (* indicates two-tailed t test p = 0.049, n = 6 mice for control, n = 5 mice for PI-88). p–w Analysis of remyelination by EM at 14 d.p.l. (n = 5 mice per group). p, r Inserts showing lesion location in ventrolateral white matter. t Proportion of remyelinated axons (* indicates two-sided t test p = 0.040) and u relationship between axon diameter and g-ratio (linear regression is shown). Frequency distribution of axonal g-ratio (v) and axon diameter (w) in lesion. *, ** indicate two-sided t test p < 0.05 and 0.01, respectively. Mean ± SEM is shown. Scale: 20 μm (a–j) and 5 μm (p–r) and 1000 nm (q–s).