Alteration of the Brain Barrier System in Pathological States

Abstract

Diseases of the central nervous system that are severe enough to alter its structural organization result in localized or generalized increase in the permeability of the blood-brain barrier. Whether a similar change in permeability can occur in alterations that are purely functional depends upon our criteria of the brain barrier system. If we consider the membranes of glial cells and neurons as part of the system, then the alteration of its permeability with concomitant ion shifts is a constant phenomenon and part of the normal function of the nervous tissue. In this chapter, we will restrict our description to gross changes in barrier permeability associated with pathological conditions. Assuming that the blood-brain barrier, although still hypothetical in structure and mechanism, is of a considerable rate-limiting importance, any change in its integrity might result in (1) increase of the rate of exchange of molecules that penetrate the normal CNS only after a measurable delay, (2) a passage of large molecules that, although present in the organism, are normally prevented from entering the internal milieu of the brain, and (3) the entrance into the CNS of abnormal molecules, either autogenous or exogenous. For many ions and molecules, the brain barrier system is not an all-or-none phenomenon; consequently for them, the pathologically increased permeability of the barrier will represent an increased exchange between plasma and nervous tissue rather than a vast inundation of the CNS such as might be envisioned to follow the opening of an imaginary flood gate. A number of pathological factors culminating in what might be called the severity of the lesion will determine the degree of permeability in terms of rate of exchange and the types of molecules involved.