Is the pial microvessel a good model for blood-brain barrier studies?

Pial microvessels have commonly been used as model systems for studying blood-brain barrier (BBB) properties instead of cerebral cortical microvessels. Since pial microvessels are relatively accessible they have been especially employed in electrophysiological and pharmacological studies. Measurements of electrical resistance across endothelial cells (EC) as a measure of their barrier properties have been made exclusively from pial microvessels in in vivo BBB studies. Similarly the observed responses of microvessels to the application of pharmacological agents have commonly been made on pial microvessels as representative of BBB vasculature. In this review the properties of pial and cerebral microvessels are compared to determine whether the use of the pial microvessel as a model for BBB studies is valid. Similarities are described in their ultrastructural features, permeability to electron dense tracers and molecular characteristics. Measurements of electrical resistance from pial microvessels are compared with measurements from cerebral EC monolayers in tissue culture and indirect determinations for cerebral microvessels in situ. Two notable differences between pial and cerebral microvessels are described in the adult nervous system. Tight junctions between cerebral EC appear to consist of a uniform population. In pial microvessels however tight junctions consist of two populations in one the inter-EC tight junctions resemble those between cerebral EC, with fusion of adjacent EC membranes. In the second population the inter-EC tight junctions differ with a discernible gap between adjacent EC membranes. The distribution of the endothelial barrier antigen (EBA) is uniform between EC of cerebral microvessels. By contrast EC of pial microvessels from a heterogeneous population for EBA expression which is related to the proximity of the EC to the astrocytic glia limitans. The role of astrocytes in the induction and maintenance of the BBB characteristics is briefly reviewed. The possible significance of the lack of an astrocytic ensheathment of pial microvessels is assessed. In summary, caution is urged in employing pial microvessels in BBB studies and the need for more information on possible pial microvessel heterogeneity is stressed.