Therapeutic considerations in blood-brain barrier disturbances

Current methods of treatment of brain damage, as e.g. edema by steroids and barbiturates, have components which benefit the blood-brain barrier. Protection of the blood-brain barrier may result from: (a) prevention of endothelial lesions, perhaps pinocytosis (b) reduction of secondary necrosis formation, (c) interference with release, or activation of mediator compounds causing endothelial lesions such as: biogenic amines, free fatty acids, prostaglandins, free radicals, or kinins, (d) stabilization of lysosomal membranes, and (e) prevention of microcirculatory disturbances. Other methods, or compounds aiming at mechanisms of barrier damage have a therapeutic potential as shown with regard to indomethacin, free radical scavengers, or phenothiazines. However, further studies appear necessary to demonstrate the benefit of these compounds under clinical circumstances. Reversible opening of the blood-brain barrier may be considered as a therapeutic approach to provide access of drugs to brain tissue which are normally excluded by the barrier.