Figure 2.

C286 Regulates Inflammatory and DNA Repair Pathways

(A) Genes were classified on the basis of their co-expression behavior over the various conditions. C286 downregulated 165 genes that had been upregulated by the injury.

(B) GO terms associated to the co-expressed genes are displayed on the basis of their confidence (−10*log10[p value]), red arrows highlight the MAPK and WNT pathways.

(C) Diagram of experimental design.

(D–G) (D and E) Representative images and quantification of FZD10 (scale bar, 100 μm and 20 μm for higher-magnification insets) and (F and G) of Daxx expression in microglia (Iba1) and neurons (βIII tubulin) in the SC at the end of the treatment period (scale bar, 50 μm). Two weeks after injury, a sub-set of vehicle- and C286-treated rats was used for immunohistological analysis (n = 3 per treatment group) and for RT-qPCR (n = 3 per treatment group).

(H–K) (H and I) Levels of P2X4R⁺ microglia (highlighted by arrows in the merged upper panel, scale bar, 30 μm) and (J and K) BDNF (in neurons and microglia) in the SC (scale bar, 30 μm).

(L and M) (L) Images showing BRCA1 expression in the same area (insets show higher magnification of BRCA1 in nuclei, scale bar, 100 μm) and (M) quantification by RT-qPCR.

(N–P) Expression and quantification of BRCA1 and pATM in spinal microglia (scale bar, 20 μm).

(Q and R) Expression and quantification of γH2AX (scale bar, 100 μm).

In E, G, I, K, O, P, and R, data are shown as Mean ± SEM of fluorescence intensity (FI) in arbitrary units (a.u.). Student's t test, **p ≤ 0.01, ***p ≤ 0.001, n = 4 (E and G) or n = 3 (I, K, M, P, and R) per group, five sections per animal).