The Morphological Approach to the Study of Normal and Abnormal Brain Permeability

Abstract

The rich capillary bed of the central nervous system (CNS) is impervious to protein. This generalization derives from two observed features of the cerebral capillary wall: (a) the tight junctions between contiguous endothelial cells comprise uninterrupted belts that arrest the passive, intercellular movement of protein and (b) the vesicles that bud off the endothelial cell membrane do not appear to carry protein across the cell from blood to perivascular tissue¹⁹. We would like to review briefly where and how this blood-brain barrier (BBB) to protein and peptide is circumvented in the normal and experimentally manipulated mammal. It will become apparent that in some vessels which are naturally permeable or rendered permeable experimentally, one or the other of both features is altered: the junctions are open and no longer tight and the endothelial plasmalemma of certain vessels is capable of vesicular transport. A third means of bypassing the barrier must still be considered as a strong suspicion rather than proven: fenestrae or round windows that perforate the attenuated endothelium of capillaries in a few specific regions are bridged by thin diaphragms that may be permeable to protein and peptide. A fourth bypass is one that we have just come to appreciate: the very axons of the neurons within the cerebral parenchyma. It is through the cytoplasm of these axons that large molecules can be brought from extracerebral, peripheral blood to neuronal cell bodies of the brain and spinal cord⁶.