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  • Title: Localized changes in blood-brain barrier permeability following the administration of antineoplastic drugs.
    Author: MacDonell LA, Potter PE, Leslie RA.
    Journal: Cancer Res; 1978 Sep; 38(9):2930-4. PubMed ID: 679202.
    Abstract:
    The effects of four antineoplastic drugs on the permeability of the blood-brain barrier to Evans blue-albumin and to horseradish peroxidase were studied in cats. Extravasation of tracer in brain tissue was observed only rarely following the injection of methotrexate, cyclophosphamide, or vincristine. However, 5-fluorouracil (15 mg/kg) caused localized Evans blue-albumin exudation in various gray and white matter areas in 8 of 13 cats to which the Evans blue was administered 7 hr after the drug injection. Electron microscopy revealed that 5-fluorouracil stimulated pinocytotic vesicular transport of peroxidase across brain capillary endothelial cells and possibly that it widened endothelial tight junctions. Barrier leakage was not observed when time periods longer than 7 hr elapsed between 5-fluorouracil injection and tracer administration, and extravasation occurred only once after a shorter time interval. These results suggest that changes in blood-brain barrier permeability observed 7 hr after 5-fluorouracil administration are reversible and of fairly short duration. Such changes may be relevant to the development of secondary intracranial tumors following antineoplastic chemotherapy.
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