Alteration of blood-brain-CSF barrier in experimental meningeal carcinomatosis. A morphologic and adriamycin-penetration study
| Autor: | Rachel Mizrachi, Uri Sandbank, Tzony Siegal, Eitan Ben-David, Raphael Catanel, Alberto Gabizon, Tali Siegal |
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| Rok vydání: | 1987 |
| Předmět: |
Male
Cancer Research Pathology medicine.medical_specialty Blood–brain barrier chemistry.chemical_compound Mice medicine Meningeal Neoplasms Animals Meningeal Neoplasm Evans Blue Cerebrospinal Fluid Tight junction Meninges Spinal cord medicine.disease Extravasation Mice Inbred C57BL medicine.anatomical_structure Meningeal carcinomatosis Neurology Oncology chemistry Blood-Brain Barrier Doxorubicin Injections Intravenous Neurology (clinical) |
| Zdroj: | Journal of neuro-oncology. 4(3) |
| ISSN: | 0167-594X |
| Popis: | An experimental model of meningeal carcinomatosis has been produced by subarachnoid inoculation of B16 melanoma cells into C57BL mice. Injection of 10(3) viable cells was sufficient to cause 100% tumor incidence and death within a median survival time of 17 days. The tumor infiltrated diffusely the meninges of the brain and spinal cord and filled the ventricular system. Electron microscopic study of the leptomeningeal tumor revealed newly formed microvessels with fenestrated endothelium. The integrity of the blood-brain barrier was studied by the extravasation of the Evans blue and the Horseradish peroxidase tracers. Barrier disruption became evident from the seventh day on, using Evans blue. Electron microscopy study showed peroxidase activity in the luminal and abluminal sides of the meningeal microvessels, and within the tight junctions. Similar findings were noted in cortical capillaries adjacent to the meningeal tumor. Brain concentrations of Adriamycin (ADR) following administration of an intravenous dose of either 10 mg/kg or 50 mg/kg were measured on days 0 to 14 after tumor inoculation. A significant increase in mean +/- SEM content of whole brain ADR was observed only with the 50 mg/kg dose in days 7 to 14 (0.69 +/- 0.02 micrograms/g wet tissue weight) as compared to tumor-free controls (0.43 +/- 0.01, p less than 0.05). Our study suggests that barrier alteration in meningeal carcinomatosis allows extravasation of tracer solutes. Still, in order to achieve a significant increase in a water soluble drug penetration through the disrupted barrier, a high-dose drug regimen is required. |
| Databáze: | OpenAIRE |
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