Fig. 7: EFV, a CYP46A1 activator, enhances neurorestoration after stroke.
a, Schematic illustrating the mechanism of EFV as a CYP46A1 activator that promotes cholesterol metabolism and neurorestoration post stroke. b, Experimental timeline depicting EFV or vehicle treatment in MCAO male mice during the chronic phase. c,d, Motor and balance functions were assessed using foot-fault (c) and rotarod (d) tests in MCAO mice treated with EFV or vehicle control; n = 8 mice per group. e,f, Cognitive function evaluation using the Y-maze test (day 72 post MCAO) (e) and NOR test (day 70 post MCAO) (f) in EFV and vehicle-treated MCAO mice; n = 8 mice per group. g,h, T2-weighted MRI images (g) and quantification (h) showing reduced brain lesion volume in EFV-treated mice compared to vehicle controls; n = 8 mice per group. i,j, MBP immunostaining (i) and quantification (j) showing improved white matter repair in EFV-treated mice compared to vehicle controls; n = 8 mice per group. k, Representative transmission electron microscope images of the basal ganglia at day 74 post MCAO; red arrowheads indicate demyelinated axons. l, G-ratio (ratio of the inner axon diameter to the total outer fibre diameter) was quantified and compared between EFV-treated and vehicle-treated groups; MCAO-EFV, n = 112 axons from three mice; MCAO-V, n = 78 axons from three mice. m,n, Lipid droplet accumulation (m) and quantification (n) in microglia from the lesion area was reduced by EFV treatment; n = 8 mice per group. o, Heatmap demonstrating downregulation of pro-inflammatory gene expression in microglia post MCAO following EFV treatment. MCAO-V, n = 4 mice; MCAO-EFV, n = 5 mice. Colour legend in n applies to all bar graphs. Data are mean and s.d. Statistical significance was assessed by two-way ANOVA (c,d) followed by Bonferroni’s multiple comparisons test or two-sided unpaired Student’s t-test (e,f,h,j,l,n). MCAO-V, MCAO-vehicle; MCAO-EFV, MCAO-efavirenz.
