The role of unstirred layers for water exchange across the blood-brain barrier

Abstract

Theoretical considerations of the influence of unstirred layers around cerebral capillaries and of the effect of cerebral capillary endothelial cells on filtration and diffusion of water across the blood-brain barrier are presented. The theoretical analyses are applied to a previously published clinical investigation in which the filtration and diffusion permeability coefficient ( P f and P d) were measured. In that study the P f P d ratio was found to be slightly above unity, have a value of 4.3. The analyses in the present study demonstrate that the unstirred layer, in the classic sense, in the extracellular fluid around the capillaries will not have any significant influence on either the measured P f or the P d value. The unstirred layer inside the cerebral endothelial cells will also be without significance on the measured P d values. However, for reasonable values of the parameters of the system, this unstirred layer may have a significant influence on the measured P f value and may cause it to appear to be larger than the true steady-state value. This is especially true for the case where the luminal endothelial cell membrane is more permeable to water than the abluminal. Thus, the fact that the measured P f might be too high can explain the observation of the P f P d ratio of 4.3 although a minimal amount of water might still be filtered through pores in the blood-brain barrier. Quantitatively these amounts are, however, negligible compared to the filtration in other organs.