Changes of fight junctions between the brain microvascular endothelial cells in rats bearing C6 glioma

Objective To investigate the changes in the tight junctions of the blood-brain barrier (BBB) in a rat model bearing C6 glioma. Methods Rat models bearing C6 glioma were established in 30 male Wistar rats by stereotactic injection of C6 glioma cells into the caudate nuclei, with another 30 rats as the normal control group. Twenty-one days after the injection, magnetic resonance imaging (MRI) was performed, and the normal brain tissue, tumor core, tumor margin and the ipsilateral hemisphere tissues 2 mm from the tumor margin were sampled for ultrastructural observation of the BBB using electron microscopy, Immunohistochcmistry and RT-PCR were used to analyze the expression of claudin-5 protein and mRNA in these tissues, respectively. Results MRI revealed tumor formation in the brain 21 days after C6 cell injection. In normal control brain tissues, the paracellular cleft between the adjacent endothelial cells was sealed by continuous tight junction strands, which were found in only 22.23% of the microvesscls in the core of the brain gliomas, and obvious paracellular clefs were found between the adjacent endothelial cells in other microvessels. In the tissues on the tumor margin, intercellular tight junctions were found in 57.15% of the microvessels with the rest microvesseis having obvious paracellular clefts. Immunohistochemistry showed strong claudin-5 positivity in the control brain tissue but yielded negative results in the core of the gliomas. Compared with the core of the gliomas, the tissues on the tumor margin, those 2 mm from the tumor margin and the control brain tissues showed significantly increased claudin-5 expression (P<0.05,respectively). Conclusion In C6 glioma-bearing rats, the continuity of the tight junctions in the BBB is interrupted due to decreased expression of claudin-5 in the brain gliomas. Key words: Brain gliomas; Blood brainbarrier; Tight junctions; Clandin-5