Fig. 5: CaV inhibition reduces pericyte-evoked capillary block by blood cells in AD.
a, Imaging cortex of NG2-dsRed WT and AD mice; FITC-dextran in blood. Yellow triangles: pericytes at blocks (Supplementary Video 6). Plot: percentage of capillary segments with blocks in 94 μm × 94 μm × 10 μm image stacks. b, Probability distribution of distance of nearest pericyte soma to block (black) in AD cortex. Magenta: prediction for pericytes uniformly spaced along capillary (Extended Data Fig. 2b) if blocks occur randomly (P value: Kolmogorov–Smirnov test). c, Percentage of blocks in different branch order capillaries from PA or AV in AD. d, In vivo imaging of Ly6G-labeled neutrophils or Iba1-eGFP-expressing monocytes in lumen (labeled with Texas Red or (left-most and top right panels) outlined by NG2-dsRed pericyte processes). Yellow arrows: left, pericyte circumferential processes; right, PVMs and monocytes (top right, monocyte also indicated by a green line). Blue boxes: blocks without neutrophils or monocytes. Graph: percentage of capillaries with blocks containing neutrophil or monocyte (Supplementary Videos 7 and 8). e, Stall duration of cells in AD cortex. f, Capillary images and diameters during neutrophil stall in AD (Supplementary Video 9). Graph: stalled neutrophils are larger than capillary lumen (without a neutrophil) where they stall. g, Stalled monocytes are not larger than capillaries they stall in. h, AD mice perfused with FITC-albumin in gelatin (re-colored red) when alive (to label patent vessels) show impaired perfusion at pericyte somata (yellow triangles). Capillary blocks contain Ly6G-labeled neutrophils (top), CD45-labeled leukocytes (bottom left) and ter119-labeled RBCs (bottom right). Aβ plaques labeled with 82E1 in top image. i–k, Nimodipine in vivo largely restores capillary perfusion (percent of vessel segments that are patent) at Aβ plaques (i, pale pink bar is for capillaries away from plaques) and reduces the number of leukocytes (j) and RBCs (k) stuck in capillaries. Note, there may be more than one cell type per block, with RBCs also present at leukocyte blocks. P values are from Mann–Whitney tests in a,d–g, and Kruskal–Wallis tests in i–k. P values are two-tailed. Error bars are s.e.m.
