Fig. 7: IL-1α-induced neuroinflammation and oligodendrocyte loss is partly mediated by endothelial IL-1R1.

a Genetic design of the Cdh5CreER::Il1r1r/r mouse line. b Quantification of Il1r1 gene expression in primary brain endothelial cells isolated from adult Il1r1r/r mice expressing an IL-1R1-knockout phenotype (set to 0%) and Cdh5CreER::Il1r1r/r mice at 30 days post-tamoxifen treatment (n = 3 mice/group). c Quantification of Ly6G+ neutrophils in the spinal cord of WT, Il1r1r/r and Cdh5CreER::Il1r1r/r mice at 24 h post-i.c.m. injection of PBS or rmIL-1α (n = 6 WT + PBS, n = 8 Il1r1r/r + PBS, n = 5 Cdh5CreER::Il1r1r/r + PBS, n = 10 WT + rmIL-1α, n = 14 Il1r1r/r + rmIL-1α, n = 9 Cdh5CreER::Il1r1r/r + rmIL-1α). d Quantification of Olig2+ CC1+ mature oligodendrocytes in the spinal cord at 24 h post-injection (n = 6 WT + PBS, n = 8 Il1r1r/r + PBS, n = 5 Cdh5CreER::Il1r1r/r + PBS, n = 9 WT + rmIL-1α, n = 14 Il1r1r/r + rmIL-1α, n = 9 Cdh5CreER::Il1r1r/r + rmIL-1α). e, f Locomotor function was assessed using the BMS score (e) and BMS subscore (f) after SCI (n = 8 mice/group). g Genetic design of the Cdh5CreER::Il1r1fl/fl mouse line. h Il1r1 gene expression in brain endothelial cells of adult Il1r1fl/fl mice, which normally express the Il1r1 gene (set to 100%), and Cdh5CreER::Il1r1fl/fl mice at 30 days post-tamoxifen (n = 2 mice/group). i Quantification of spinal cord-infiltrated neutrophils at 24 h post-injection (n = 8 WT + PBS, n = 6 Il1r1fl/fl + PBS, n = 7 Cdh5CreER::Il1r1fl/fl + PBS, n = 8 WT + rmIL-1α, n = 4 Il1r1fl/fl + rmIL-1α, n = 11 Cdh5CreER::Il1r1fl/fl + rmIL-1α). j Quantification of mature oligodendrocytes at 24 h post-injection (n = 8 WT + PBS, n = 6 Il1r1fl/fl + PBS, n = 7 Cdh5CreER::Il1r1fl/fl + PBS, n = 8 WT + rmIL-1α, n = 6 Il1r1fl/fl + rmIL-1α, n = 9 Cdh5CreER::Il1r1fl/fl + rmIL-1α). k, l BMS scores (k) and subscores (l) after SCI (n = 7–8 mice/group). Data are means + /− SEM and statistical significance was determined by a two-tailed Student’s t-test (b, h), two-way ANOVA (c, d, I, j), or two-way repeated measures ANOVA (e, f, k, l) followed by Bonferroni post-hoc test. e, f ****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05; &&&&p < 0.0001, &&&p < 0.001, &&p < 0.01, &p < 0.05. Other pairwise comparisons and p-values are indicated in graphs.