Vascular and endothelial density increase in db/AD mice. (a - b) Immunohistochemical staining for smooth muscle α-actin indicates that the brains of db/AD mice are more vascularized. (c - d) SEM images of the brains subjected to vascular corrosion casting show a similar increase in the density of the cerebrovasculature. (e) Median vascular density scores of SEM images from three blinded, independent raters (* = p ≤ 0.05, ** = p ≤ 0.01 compared to WT, Mann–Whitney U-test). Endothelial cells were also directly counted on five randomly-selected arteries / animal (* = p ≤ 0.05 compared to WT; Kruskal-Wallis ANOVA). Direct measurement of cell size (68 ± 27 cells / animal) from the middle cerebral artery indicated that db/AD endothelial cells were smaller (F[3,8] = 7.8, p < 0.01) than those from WT mice, and as expected size was inversely correlated with density (R
2 = 0.41, p < 0.02; not shown). (f) Endothelial cell density was also correlated with vascular density (p = 0.03).