Localized changes in blood-brain barrier permeability following the administration of antineoplastic drugs.
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.
D000418:Albumins / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism; D002415:Cats; D003520:Cyclophosphamide / Q000494:pharmacology; D005070:Evans Blue / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology; D006735:Horseradish Peroxidase / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology; D013997:Time Factors; D014750:Vincristine / Q000494:pharmacology
D000418:Albumins; D000970:Antineoplastic Agents; D005070:Evans Blue; D014750:Vincristine; D003520:Cyclophosphamide; D006735:Horseradish Peroxidase; D005472:Fluorouracil; D008727:Methotrexate