A previous work reported an increased permeability of brain microvascular endothelial cells co-cultured with GBM cells, caused by the down-regulation of occludin, ZO1, claudin-3 and claudin-5: the increase in permeability was smaller with low-grade astrocytoma (WHO grade II glioma) and anaplastic astrocytoma (WHO grade III glioma) compared to GBM (WHO IV glioma) [43]. This evidence concerns the gene CLDN5 and central nervous system cancer.