Examination of blood‐brain barrier (BBB) integrity in a mouse brain tumor model

Abstract

The present study examines, on a functional and biochemical level, brain tumor‐induced alterations in capillary endothelial cells forming the blood‐brain barrier (BBB). Tumors were induced by injecting Lewis Lung carcinoma (3LL) cells into the right hemisphere of female Balb/c mice. Changes in BBB permeability were assessed at various stages of tumor development, using both magnetic resonance imaging (MRI) and radiolabeled permeability markers. The expression of P‐glycoprotein (P‐gp) in the BBB was also evaluated using Western Blot. Median mouse survival following 3LL injection was 15 days. Tumor volume progressed from 1.38 mm3 on day 7 to approximately 78 mm3 on day 15. Histological and MRI analysis indicated the resulting tumor mass was restricted to the right hemisphere. The permeability of the BBB to 3H‐mannitol was similar in both hemispheres at 7 and 10 days post‐injection. At day 12 and 15, significant increases in BBB permeability was observed. The alterations in BBB permeability were associated with an increase in cerebral vascular volume, but P‐gp expression was unaffected at all stages of tumor development. The BBB is largely intact during tumor development with disruptions only observed at the later stages. Furthermore, the BBB expression of P‐gp is unaffected by tumor progression despite an increased angiogenesis in the tumor bearing hemispheres.Funding support provided by PHS Grant R01‐CA93558.