(A) Plots of the CD11b mean fluorescent intensity of microglia in the contralateral hemisphere of tumor bearing mice. There was significant decrease of microglial CD11b MFI in CSF-1R inhibitor treated mice. there was significant CSF-1R treatment effect F(1,14) = 38.77, p<0.0001 with no significant fWBI effect or interaction. (B) Quantifications of Iba1 +signal covered area. two-way ANOVA revealed significant PLX5622 treatment effect, F(1,13) = 39.14, p<0.0001, no significant radiation effect F(1,13) = 0.01122, p=0.9173 and significant interaction between PLX5622 treatment and fWBI, F(1,13) = 4.793, p=0.0474. There was a trend of increase in the tumor +DT + fWBI group (p=0.3044), and significant reduction in the tumor +DT + PLX group (*p=0.0381) and the tumor +DT + PLX+fWBI group (**p=0.0017), compared to the tumor +DT group. (C) Quantifications of CD68 +signal covered area. Two-way ANOVA revealed significant CSF-1R inhibitor treatment effect, F(1,13) = 53.07, p<0.0001, no significant radiation effect F(1,13) = 3.559, p=0.0817, and significant interaction F(1,13) = 7.529, p=0.0167. (D) Representative images of Iba1 and CD68 staining, showing Iba1 staining in red, CD68 staining in white and DAPI in blue. Scale bar = 50 um. (A-C, Two-way ANOVA with Dunnett’s multiple comparisons test vs the tumor +DT group, ns = not significant, *p<0.05, **p<0.01. each dot represents value from one mouse (A) or the mean values of Iba1 and CD68 (B and C) staining quantification of 3 snapshots in the hippocampus, N = 4–5. Error bars show mean ±SEM.