FIGURE 2.

Proposed model of leukocyte recruitment due to altered BBB integrity in GBM. A, Under normal conditions, the dual layers of the BBB is maintained through tight junctions between capillary endothelial cells and the glia limitans, which is comprised of astrocytic end-foot processes. In the postcapillary venules, these 2 layers separate creating a perivascular (Virchow-Robin) space, which contains resident macrophages. B, In the context of GBM or inflammation, the BBB is disrupted. The glia limitans loses polarity due to altered expression of AQP4 in the astrocytic end-foot processes leading to expansion of the perivascular space and communication with the underlying parenchyma (1). The capillary tight junctions are disrupted due to reduced expression of claudin-3, which permits exchange of solutes, antigens, and chemokines/cytokines (2). It also allows circulating leukocytes, such as neutrophils, monocytes, and T cells, to gain access to the perivascular space where they interact with APC that present tumor antigen from the parenchyma (3). AQP4, aquaporin 4 molecule; BBB, blood–brain barrier; GBM, glioblastoma.