Mediators of Blood-Brain Barrier Dysfunction and Formation of Vasogenic Brain Edema

Abstract

The characteristics and mechanisms enabling the blood-brain barrier (BBB) to maintain the milieu of the brain have been reviewed in detail elsewhere (Banks and Kastin, 1987; Bradbury, 1985; Crone, 1986a, 1987; Cornford, 1985; Davson, 1976; Er­ misch et aI. , 1985; Fenstermacher, 1985; Gjedde, 1983; Goldstein and Betz, 1986; Meisenberg and Simmons, 1983; Oldendorf, 1974; Pardridge, 1983; Rapoport, 1976a; Rapoport and Robinson, 1986). Before discussing the possible role of mediators in BBB opening some pertinent aspects of the BBB will be discussed briefly. The morphological substrate of the BBB in cere­ bral vessels is the continuous layer of endothelial cells with junctions and no or minimal vesic­ ular transport. The functional characteristics of BBB are the same as of tight epithelium such as (a) low diffusional permeability for water-soluble compounds, (b) low hydraulic conductivity, (c) high reflection coefficient, and (d) high electrical resis­ tance. All these parameters are indicative of low diffusional exchange of water-soluble solutes. As well as by the restricted diffusion the penetration of several mediators is also inhibited by an enzymatic degradation at the endothelial border. Although li­ pophilic compounds can easily cross the BBB by simple diffusion, the trans cellular transport of hy­ drophilic solutes is made possible by facilitated dif­ fusion and active transport. All these mechanisms permit a highly selective exchange between blood and brain and provide an optimally controlled ho-