The path of cerebrospinal fluid (CSF) movement and its influence on the distribution and elimination of substances from the CSF system have been analyzed and discussed in light of the new hypothesis of CSF physiology. According to the new hypothesis, CSF movement does not occur as a unidirectional slow circulation, but the permanent rhythmic systolic- diastolic pulsation of CSF volume. That kind of fluid movement also represents the main force in substances distribution along the CSF system and from CSF via peri- and paravascular routes into the central nervous system (CNS) parenchyma interstitial space. Our results from free moving dogs and cats suggest that the distribution of substances along the CSF system is observed in all directions, i.e. in the direction of imagined circulation as well as in the opposite direction, and depends on the resident time of the distributed substance, whereby longer resident time means longer path of distribution. The fast disappearance of organic anions from the central CSF compartments (cisterna magna, cisterna basalis), and very low concentration of the tested substances in “peripheral” CSF compartments (cortical and lumbar subarachnoid space) were observed in control condition. However, when active transport was blocked in animals by probenecid, the concentrations of monitored substances in CNS tissue and in „peripheral“ CSF compartments were significantly increased (during the same period of time) in comparison to the control group. Results of our studies suggest that the key role in the process of substances elimination from CSF belongs to the transport mechanisms that take place at a huge microvessels network inside the CNS. If the transport mechanism is occupied, then the substance will be distributed by CSF movement along the CSF system to the adjacent CNS tissue where transport from the interstitial space via capillaries is available. Our results suggest that transport at the capillary endothelium has the most important role in CNS homeostasis and in removal of potential toxic CNS metabolites out from the CNS tissue into blood circulation.
