Effect of molecular weight on tracer influx into the brain after lumbar intrathecal infusion. (A-B) Coronal brain slices show penetration of large molecular weight FITC-conjugated dextran (FITC-d500, MW 500kD) and small molecular weight Texas Red-conjugated dextran (TR-d3, MW 3kD) 120 min after lumbar intrathecal co-infusion. FITC-d500 is largely confined to perivascular spaces (B, arrows), while TR-d3 moves readily though the brain parenchyma from perivascular spaces (A, arrows) or from the pial surface (arrowheads). (C-F) Quantification of fluorescent tracer influx into anterior (C-D) and posterior (E-F) brain after lumbar intrathecal infusion, anatomically subdivided into cortex, white matter, subcortical structures, and hippocampus.(*P < 0.05, *P < 0.01 cortex vs. subcortical structures; ##P < 0.01 cortex vs. white matter; †P < 0.05, ††P < 0.01 cortex vs. hippocampus; 2-way ANOVA; n = 3-4 per time point).