Biomedical Engineering Reference
In-Depth Information
submembranal plaque proteins h- or g-catenin, which are linked to the actin
cytoskeleton via a-catenin. In addition to supporting the barrier function,
AJs mediate the adhesion of brain endothelial cells to each other, the initia-
tion of cell polarity and the regulation of paracellular permeability [17].
3.2 Blood-brain barrier transport systems
There are different mechanisms by which solutes move across membranes
as they enter and leave the brain. The transport may occur due to diffu-
sion, either simple diffusion or facilitated transport across aqueous chan-
nels (Figure 3-1). Passive diffusion is a concentration gradient dependent
process that allows molecules to move across cellular membranes between
cells (paracellular way) or across cells (transcellular way) down their electro-
chemical gradient without the requirement of metabolic energy. Small
water-soluble molecules simply diffuse through the TJs but not to any great
extent. Small lipid soluble substances like alcohol and steroid hormones
penetrate transcellularly by dissolving in their lipid plasma membrane. In
addition to concentration differences, other factors can affect the diffusion
of a drug across the BBB such as lipophilicity and molecular weight. Only
lipid soluble small molecules with a molecular weight of 400 Daltons can
cross the BBB. However, the majority of small molecule drugs have a higher
molecular weight or current water solubility which prevents their simple
diffusion across the barrier. In addition, even though some small molecules
such as HIV protease inhibitors exhibit a high degree of lipophilicity, their
CSF and brain concentrations are often undetectable [18]. This effect is
Figure 3-1
Molecular transport across the blood-brain barrier.
