Fig. 5: Cholesterol crystal deposition contributes to microglia-mediated chronic neuroinflammation and hinders white matter repair in mice.
a, Experimental design for cholesterol crystal (CC) injection into the brain parenchyma, investigating their long-term effects on microglial activation and myelin repair. b,c, IBA1 immunostaining (b) and quantification (c) demonstrate sustained microglial activation after cholesterol crystal injection compared to saline controls; n = 3 mice per group. d,e, Cholesterol crystal injection immunostaining (d) and quantification (e) demonstrate impaired white matter repair, evidenced by increased MBP loss compared to vehicle controls; n = 3 mice per group. f, Heatmap showing upregulation expression of inflammation-related genes in microglia 90 days after cholesterol crystal injection compared to control; n = 3 mice per group. g, GSEA identifies upregulation of inflammatory and immune-related pathways in cholesterol crystal-injected microglia. NES and P values are shown for each gene set; n = 3 mice per group. h, Gene Ontology enrichment analysis revealed significant enrichment of immune and inflammatory response pathways, further supporting cholesterol crystal-induced neuroinflammation; n = 3 mice per group. Data are mean and s.d. Statistical significance was assessed by two-way ANOVA followed by Bonferroni’s multiple comparisons test (c,e) or a one-sided permutation test, and the resulting P values were adjusted for multiple comparisons (g).
