Hyperosmotic blood-brain barrier disruption in brains of rats with an intracerebrally transplanted RG-C6 tumor.

To test the results of blood-brain barrier (BBB) disruption in the treatment of brain tumor, RG-C6 glioma was transplanted into the brains of rats. Intracarotid infusions of normal saline and hyperosmotic mannitol were then made, followed by intravenous injection of Evans blue dye plus albumin (EB, MW 68,000), horseradish peroxidase (HRP, MW 40,000), and 5-fluorouracil (5-FU, MW 130). Uptake of the drug and the consistency of drug levels in the normal brain and tumor varied widely among these three agents. Both EB and HRP penetrated the brain tumors but did not stain the normal brain tissues. After BBB opening, penetration of EB and HRP into the normal brain was drastically increased; however, the uptake of EB and HRP in the tumor was not increased. The concentration of 5-FU in the tumor was higher than that in the serum and, although it increased 1.5-fold after BBB opening, the increase was not statistically significant. Conversely, there was a progressive increase in concentrations of 5-FU in the tumor-free brain regions (p less than 0.05). These observations suggest that an intracarotid infusion of hyperosmotic mannitol may increase neurotoxicity because it allows greater delivery of anticancer drugs into the normal brain tissue than into the tumor tissues.