Alteration of blood-CSF barrier by tumor invasion into the meninges

Abstract

✓ Cyclophosphamide and 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) were found to have an equivalent cytostatic effect in rats with subcutaneous transplants of Walker 256 carcinosarcoma. Rats with meningeal carcinomatosis received a single intravenous dose of cyclophosphamide (30 mg/kg) or ACNU (15 mg/kg) at various times after intracisternal inoculation of 1 × 104 Walker 256 carcinosarcoma cells. Cyclophosphamide, administered 1 day after tumor inoculation, failed to prevent tumor growth in the subarachnoid space. The survival time of these rats was prolonged only 10% to 14% compared to the controls, while ACNU produced a maximum increased survival time of 180%. If administered 2, 3, 4, and 5 days after tumor inoculation, both drugs were effective; cyclophosphamide yielded a maximum increase in median survival time of 109%, 94%, 90%, and 52%, and ACNU 127%, 139%, 240%, and 100%, respectively. These results indicate that the blood-cerebrospinal fluid (CSF)...