Computer simulation of the blood-brain barrier: a model including two membranes, blood flow, facilitated and...

A mathematical model of blood-brain barrier (BBB) transport was developed to assist in experimental design and data analysis. The model includes the luminal and antiluminal endothelial cell membranes, each with separate transport systems. Substrate movement between 3 compartments can be calculated: the capillary lumen, the endothelial cell cytoplasm, and the brain parenchyma. Blood flow, substrate concentration and competition in each compartment, concentration gradients along the capillary, and non-steady-state conditions are considered. The utility of the model is demonstrated by predicting: (1) complex concentration profiles along the length of the capillary lumen under different circumstances, (2) the permeability-surface area products along the capillary lumen, (3) the time course of events during brain-uptake index (BUI) experiments, (4) the accuracy of the BUI in measuring glucose transport over a range of endogenous glucose concentrations, (5) the influence of 2 membranes in series with different kinetic constants, and (6) a comparison of kinetic constants expected from high-flow infusion and BUI experiments.