Morphology of Glial Blood‐Brain Barriers

Abstract

Glial cells, in certain situations in the CNS, may become modified to form the structural basis of the blood-brain barrier. This occurs in more primitive vertebrates, such as the elasmobranch fish, and in some higher invertebrates. In the latter, the outermost glial sheath, often called the perineurium in avascular ganglia, substitutes functionally for the vascular endothelium of higher organisms. The intercellular junctions between the lateral borders of these modified glial or perineurial cells may be of several types. In nearly all cases, adhesive and communicating (gap) junctions are found together with an occluding junctional structure. The latter is assumed to be the morphologic basis of the observed blood-brain barrier. It varies in nature and may be one in which the adjacent cell membranes fuse, partially or completely, to form a classical tight junction, or it may be one in which the cell membranes remain separated by a distinct intercellular cleft. If the latter, the cleft may be straddled by columns or septal ribbons, between which a charged matrix substance may be found. Restrictive linker junctions, recently found to be the basis of the interglial barrier in cephalopod CNS, as well as that of myriapods, are characterized by cross-striations or columns which, in combination with charged residues, inherent either in them or in the associated extracellular matrix, slow down the entry of exogenous molecules. Septate junctions, which occur between glial cells in certain other invertebrates, exhibit intercellular septal ribbons, which do not prohibit paracellular transport of all substances but may slow down the passage of some by virtue of charged moieties. There is an association of cytoskeletal components with these septate, linker, and tight junctions; the role of the cytoskeleton in tight junctions, which can be seen by freeze fracture to be based on simple ridges in insects or a more complex network of them in arachnids, may also be important in the regulation of paracellular permeability. The structural details of the junctions in different groups are summarized and their physiologic implications discussed.