A quantitative study of blood-brain barrier permeability ultrastructure in a new rat glioma model

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Abstract
Cerebral edema, a major complication of tumors in the brain, is the result of an alteration in the blood-brain barrier (B-BB). The vascular ultrastructural changes that underlie edema formation have been described in a variety of tumors. Interendothelial junction abnormalities, fenestrations, and large numbers of tubulo-vesicular profiles in the tumor vascular endothelium have been presumed to represent permeability routes that permit the escape of serum constituents into the tumor, from where they flow into the surrounding brain. Descriptive studies do not provide information on the relative frequency of these presumptive permeability routes. In the study reported here we have quantified ultrastructural features associated with the B-BB in the vessels of an experimental glioma in rat. We found that approximately 60% of the tumor vessel profiles have junctional abnormalities and 30% have one or more fenestrations. The density of tubulo-vesicular profiles, however, was not increased. In addition, tumor vessel walls were thicker than normal vessels of the same caliber and the mitochondrial density was in the range of that for non-barrier vessels. Vessels in peritumoral regions were not altered in any of the parameters measured.