Estimation of capillary permeability of inulin, sucrose and mannitol in rat brain cortex

Abstract

The present study analyzed the brain uptake of the differently sized hydrophilic molecules 14C-inulin, 14C-sucrose and 14C-mannitol. constant tracer concentrations were maintained in blood plasma after renal ligation. Accumulation of the indicators was measured in brain cortex during the approach to steady-state. At the conclusion of infusion periods of 5, 10, 15, 30 and 60 min, samples of cerebral cortex were analyzed for radioactivity. Fractions attributable to blood in the tissue were subtracted and time-dependent apparent distribution volumes of the indicators in the tissue were estimated. The brain level did not rise to more than 1--2% of that in the plasma for inulin and sucrose and to 6--7% for mannitol. The explanation for this could be a combination of restricted penetration from blood into brain and a sink effect of cerebrospinal fluid (csf). to determine the removal of the indicators into csf, ventriculo-cisternal perfusion was performed during the period of tracer uptake in the the tissue; the rate of passage of the indicators into perfusion fluid was found to be negligible in comparison to the rates of uptake in the tissue. As diffusion in the extracellular space could limit uptake rates from blood to brain, estimates of diffusion limited half-times were also made. Calculations showed that the major hindrance to indicator uptake in the tissue is located in the wall of the brain capillaries; thus the uptake data permit calculation of brain capillary permeability. The half-times for the distribution of the indicators in their equilibrated tissue distribution spaces were used to estimate brain capillary permeability. By comparison with the aqueous diffusion coefficients of the indicators it is concluded that the substances in the molecular weight range of 182 to 5 500 daltons are subjected to restricted diffusion during the passage of the blood-brain barrier and that in addition non-discriminative transendothelial pathways are available.