TLR4 and diabetes mellitus: Figure 2 shows that T1DM significantly increased RAGE, MMP9 and TLR4 expression compared to non-DM rats at 10 weeks after diabetes induction (p<0.05, Figure 2A–C). Figure 2D–F show that RAGE, TLR4 and MMP9 are predominantly detected in macrophages (ED1 positive cells) in the cerebral arteries. The results are consistent with previous studies [14], [20]. In addition, Figure 2G–I show that the increase of RAGE (r = 0.532, p<0.01; Figure 2G), TLR4 (r = 0.634, p<0.001; Figure 2H) and MMP9 (r = 0.522, p<0.02; Figure 2I) expression significantly correlated with IA formation in T1DM rats.