The vasculature of experimental brain tumours. Part 4. The quantification of vascular permeability

In order to quantify changes in vessel permeability seen previously in experimental astrocytomas produced in rats by an intracerebral injection of cultured neoplastic glial cells, the flux of mannitol across the vascular endothelium from the blood into the normal brain or tumour tissue was measured using a specially devised technique by which a steady level of radioactively labelled mannitol can be achieved rapidly and maintained in the bloodstream. This is done by a continuous injection given at a rate which is adjusted by a predetermined programme so as to replace the tracer at the rate at which it has been found to leave the circulation in previous experiments. In separate experiments on both tumour-bearing and control rats steady levels of the tracer were maintained in the circulation for progressively longer times of up to 30 min. The kinetic parameters of the process gave estimates for the apparent transfer constant of mannitol across the vascular endothelium and of the size of the extravascular extracellular mannitol space in the tumours. The apparent transfer constant for the movement of mannitol across the blood-brain barrier was increased more than a hundred-fold in the region of the tumour compared to the values for the brain of control rats or that of tumour-bearing rats remote from the tumour site. The extracellular extravascular space within the tumour was estimated to be 22%, somewhat larger than accepted normal values.