The brain microvascular network is comprised of capillaries, arterioles and venules, all of which retain - although to a different extent - blood-brain barrier (BBB) properties. Capillaries constitute the largest and tightest microvasculature. In contrast, venules have a looser junctional arrangement, while arterioles have a lower expression of P-gp. Development and maintenance of the BBB depends on the interaction of cerebral endothelial cells with pericytes and astrocytes, which are all heterogeneous in different regions of the central nervous system. At the level of circumventricular organs microvessels are permeable, containing fenestrations and discontinuous tight junctions. In addition, the blood-spinal cord barrier - where the number of pericytes is lower and expression of junctional proteins is reduced - is also more permeable than the BBB. However, much less is known about the cellular, molecular and functional differences among other regions of the brain. This review summarizes our current knowledge on the heterogeneity of the brain microvasculature.

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The blood-brain barrier (BBB) is the main interface controlling molecular and cellular traffic between the central nervous system (CNS) and the periphery. It consists of cerebral endothelial cells (CECs) interconnected by continuous tight junctions, and closely associated pericytes and astrocytes. Different parts of the CNS have diverse functions and structures and may be subject of different pathologies, in which the BBB is actively involved. It is largely unknown, however, what are the cellular and molecular differences of the BBB in different regions of the brain. Using in silico, in vitro, and ex vivo techniques we compared the expression of BBB-associated genes and proteins (i.e., markers of CECs, brain pericytes, and astrocytes) in the cortical grey matter and white matter. In silico human database analysis (obtained from recalculated data of the Allen Brain Atlas), qPCR, Western blot, and immunofluorescence studies on porcine and mouse brain tissue indicated an increased expression of glial fibrillary acidic protein in astrocytes in the white matter compared with the grey matter. We have also found increased expression of genes of the junctional complex of CECs (occludin, claudin-5, and α-catenin) in the white matter compared with the cerebral cortex. Accordingly, occludin, claudin-5, and α-catenin proteins showed increased expression in CECs of the white matter compared with endothelial cells of the cortical grey matter. In parallel, barrier properties of white matter CECs were superior as well. These differences might be important in the pathogenesis of diseases differently affecting distinct regions of the brain.