Neuropharmacologic control of cerebral capillary permeability: current implications for therapy of vasogenic brain edema

Vasogenic brain edema occurs as a result of a diverse spectrum of central nervous system pathology. The fundamental physiologic abnormality of vasogenic brain edema is an increase in cerebral capillary permeability. It is hypothesized that the recent development of new, potent, synthetic vasopressin antagonists will make it possible to impede the formation of vasogenic brain edema by the intraventricular administration of such agents with the subsequent inhibition of the neural control of brain capillary permeability by the locus ceruleus. The action of the vasopressin antagonists should be synergistic with the anti-edema effects of central alpha-adrenergic blockade produced by phentolamine. The combination of these two modes of therapy is expected to produce an increase in intracranial pressure which will require additional forms of medical therapy to control, in spite of the overall decrease of brain parenchymal water content.