Fig. 4

Reduced CC flow in ApoE4-TR mice before and after BCAS. a Rendering of in vivo 3-photon excited fluorescence/third harmonic generation (3PEF/THG) image stack that spans from the cortical surface to the white matter (WM) of the corpus callosum (CC) in ApoE3-TR mice. The vasculature was visualized by the THG signal (white), and was also labeled with FITC-dextran (red). The images to the right (A1–A5) show 40-µm thick maximal microvascular projections, centered at the indicated depths. Scale bar in A5 = 50 µm. b–e Projections (20 µm thick) of 3PEF/THG image stacks and line scans for capillaries in the CC, taken at the indicated depths from the cortical surface, of ApoE3 and ApoE4 mice at baseline and at one month after BCAS. Scale bars in E are 10 µm and 50 ms, respectively. f, g Plot of diameter (f) and RBC flow speed (g) in individual CC capillaries at the depth between 800–1000 µm in the same mice at baseline and 4 weeks after BCAS (ApoE3 baseline n = 80 in four mice, ApoE4 baseline n = 85 in four mice, ApoE3 BCAS n = 118 in four mice, ApoE4 BCAS n = 73 in three mice). Data are expressed as means ± SEM. * p < 0.05 from ApoE3-Baseline; ^# p < 0.05 from ApoE3-BCAS and ApoE4-Baseline; Kruskal-Wallis test