(A) Confocal images showing the distribution of 10, 70 and 2000 kDa fixable dextrans in brain 60 min after their co-injection into the cisterna magna. The lower panels show a higher magnification view of the boxed region in the top right panel. (B) (left) Profile of dextran fluorescence, normalized to fluorescence at the brain surface, as a function of distance from the cortical surface for the rectangular region shown in the lower right panel in A. (right) Cortical depth at which measured fluorescence intensity decreases to half its value at the cortical surface (d1/2, circles, left axis, n = 5 mice, black bars mean ± S.E.M.), and the relative distance that each fluorophore is predicted penetrate in 60 min by diffusion alone (asterisks, right axis). (C) Confocal image of brain cortex 60 min after cisternal injection showing fluorescence along the paravascular space of a penetrating arteriole. (D) (left) Relative fluorescence as a function of distance from the parenchymal surface in the paravascular space outlined on the right of C, measured for each dextran. (right) Distance at which fluorescence intensity decreases to 10% of its initial value (mean ± S.E.M., seven arterioles). (E) High magnification confocal slice through a cortical penetrating arteriole showing subtle differences in the distributions of 10, 70 and 2000 kDa fixable dextrans in the paravascular sheath at 60 min after cisternal injection.