Changes of the blood-brain barrier in experimental metastatic brain tumors

An experimental model for blood-borne cerebral metastases was developed by introducing Walker 256 carcinoma cells selectively into the intracranial internal carotid artery of rats. This model was used to study the regional capillary permeability of rat brain and metastatic brain tumors of various sizes with the aid of 14C alpha-aminoisobutyric acid (AIB) quantitative autoradiography. The regional capillary permeability varied with the anatomical location and size of the tumor. Intraparenchymal tumors less than 1 mm in diameter showed no increased permeability to AIB. As the tumors enlarged over 1 mm in diameter, the permeability in the intraparenchymal tumors increased proportionally, but remained less than one-third of capillary permeability of subcutaneously transplanted tumors. Capillary permeability in the peripheral invasive part and necrotic center was less than in the viable part of large tumors. Capillary permeability in metastatic tumors of the choroid plexus and meninges was significantly higher than in tumors of the brain parenchyma. The results suggest that the uptake of chemotherapeutic agents that do not cross the blood-brain barrier easily varies with the anatomical location and size of the metastatic tumors.