Drug "diffusion" within the brain.

1. The rates and the ways different materials move from ventricular fluid into and through the caudate nucleus vary rather broadly. 2. The major mechanism of solute flow from ventricular CSF into and through the caudate nucleus appears to be simple diffusion. 3. Among solutes that pass across the BBB from brain to blood at very low rates, those that distribute mainly or exclusively in the extracellular space (e.g., sucrose, EDTA, and sodium) "diffuse" most rapidly into the caudate nucleus. 4. Among solutes which efflux across the BBB at very low rates, the apparent rate of diffusion within the caudate nucleus is the least for those that are readily taken up and accumulated by brain cells (e.g., AIB). 5. Solutes that move moderately to rapidly across the BBB from brain to blood only penetrate distances of several mm or less into the caudate before they are completely cleared from the tissue by the cerebral circulation. 6. In most instances the slopes of the tissue concentration profiles within the caudate nucleus during and after ventriculocisternal perfusion are fairly steep and are complex functions of parameters such as the effective tissue diffusion coefficient (Dt) and the transcapillary efflux rate constant (Ko), each of which are, in turn, dependent on separate sets of variables (e.g., the rate of cellular uptake for Dt and the rate of blood flow for ko). 7. The distribution process and kinetics may be much different in CNS areas adjacent to the subarachnoid space than in the caudate nucleus because of convective flow of subarachnoidal CSF through the perivascular spaces of the penetrating and emerging blood vessels and the arterioles and venules.