Parenchymal and perivascular uptake of fluorescent dextrans applied directly to the brain surface under constant pressure conditions. (A) Experimental setup in which dyes in a cylindrical pipette with overlying layer of oil contact the brain surface to clamp pressure at a specified value. (B) Hematoxylin and eosin staining of brain following craniotomy and durotomy. p, pia; s, skull. The enlarged subarachnoid space is a tissue-processing artifact. (C) Left: Distribution of 70-kD fluorescent dextran uptake in brain after 20-min application at low and high pressures. Right: Distribution of 2,000-, 70-, and 10-kD fluorescent dextrans in the boxed region at the left. (D) Fluorescence of each dye from the brain surface along the rectangular areas shown in C normalized to the intensity at the brain surface. (E) Depth of dye penetration in the perivascular and parenchymal spaces of the cortex following 30 min of direct application at low or high pressure. (*^1–3, P < 0.001; n.s.^2,3, P > 0.999, repeated-measures two-way ANOVA with Bonferroni posttest).