The effect of dexamethasone on vascular permeability of experimental brain tumours

Abstract

The vessels of experimental gliomas show an abnormally high permeability to small polar molecules, such as mannitol. To establish whether this change in vessel permeability is modified by treatment with the corticosteroid dexamethasone, the kinetics of [14C]mannitol transfer into rat astrocytomas were estimated in both steroid-and saline-treated, tumour-bearing animals. This was achieved by injecting [14C]-mannitol i.v., using a specially devised technique, so as to maintain a constant concentration of tracer in the blood plasma. In separate experiments steady levels of the tracer were maintained in the circulation from 1 to 30 min. Mean plasma and tumour radioactivity were measured, and the apparent transfer constant of mannitol across the vascular endothelium and the size of the extravascular extracellular mannitol space in the tumours were calculated. Despite a significant clinical improvement in the treated animals and adequate circulating levels of dexamethasone at the time of the permeability studies, no difference in either the apparent transfer constant for the movement of mannitol into the tumours or the fractional extracellular mannitol space was detected between these animals and the controls. With steroid treatment both tumour-bearing and non-tumour bearing animals lost weight, and in the latter there was no consistent change in routine biochemical or haematological parameters. It was concluded that under these conditions it is unlikely that clinical improvement with dexamethasone therapy was due to a non-specific reduction in tumour vessel permeability to polar substances.