Brain edema: pathogenesis and therapy.

Abstract

In the brain intravascular and interstitial spaces are separated by a highly specialized endothelial lining, which is the morphological substrate of the blood-brain barrier (BBB). Under physiological conditions the BBB exerts rigid control of water soluble compounds moving from blood into brain and from brain into blood, respectively. Under pathological conditions such as trauma or ischemia, an increase in BBB permeability may occur that allows plasma constituents to escape into the brain tissue. This "opening" of the BBB may, at least in part, be due to a massive release of autacoids, which thus act as mediators of vasogenic brain edema. Five criteria have to be fulfilled by a given autacoid to be considered a mediator candidate: (i) a permeability-enhancing action under physiological conditions; (ii) a vasodilatory action; (iii) the ability of inducing vasogenic brain edema; (iv) an increase of concentration in tissue or interstitial fluid under pathological conditions; and (v) a decrease of brain edema by inhibiting the release or action of a given autacoid. Among the mediator candidates discussed, only bradykinin fulfills all these criteria. Histamine, arachidonic acid and free radicals, including nitric oxide, may also be considered mediator candidates of brain edema, but for each of these compounds evidence is less clear than for bradykinin. Although the concept of autacoids mediating brain edema is well established and supported by experimental data, it has not yet gained entrance into the clinics. Treatment of patients suffering from vasogenic brain edema is symptomatic and mainly concentrated on the control of intracranial pressure.