Solutes in CSF have rapid access to ECS throughout the CNS (within 5-10 min). This occurs by solute/fluid influx through PVS around penetrating arteries, followed by longitudinal spread along the BL of capillaries to reach venules and veins. These paravascular pathways can be demonstrated light-microscopically by infusion of the tracer protein, HRP, into SAS and the subsequent localization of this probe molecule in brain sections using the sensitive histochemical method based on TMB. This unidirectional tracer/fluid movement along the intraparenchymal vascular network, with accompanying spread into the cerebral interstitium, appears to be facilitated by the pulsation of penetrating arterioles within their PVS with each cardiac contraction.