Differential permeability of the blood-brain barrier in experimental brain metastases produced by human neoplasms implanted into nude mice

Am J Pathol. 1992 Nov;141(5):1115-24.


This study clarified whether and when the blood-brain barrier in experimental brain metastases is impaired by using hydrosoluble sodium fluorescein (MW 376) as a blood-brain barrier function indicator. Cells from eight human tumor lines (four melanomas, two breast carcinomas, one colon carcinoma, and one renal carcinoma) were inoculated into the internal carotid artery of nude mice. Brain metastases at different stages of development were sampled and the permeability of the blood-brain barrier around the metastases determined. Histologic examination showed two patterns of tumor growth. In the first, tumor cells formed isolated, well-defined nodules in the parenchyma of the brain. In lesions smaller than 0.2 mm2, the blood-brain barrier was intact. In the second, small diffuse nests of tumor cells were distributed throughout the brain parenchyma. The blood-brain barrier was intact until the small tumor cell colonies coalesced to form large tumor masses. These results suggest that the permeability of the blood-brain barrier varies among different experimental brain metastases and that its function is related to the growth pattern and size of the lesions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood-Brain Barrier / physiology*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / physiopathology*
  • Brain Neoplasms / secondary
  • Breast Neoplasms / pathology
  • Cell Membrane / physiology
  • Cell Membrane / ultrastructure
  • Cell Membrane Permeability / physiology*
  • Colonic Neoplasms / pathology
  • Fluoresceins
  • Humans
  • Kidney Neoplasms / pathology
  • Melanoma / pathology
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Tumor Cells, Cultured


  • Fluoresceins