FIGURE 5.

Endothelial activation‐induced blood–brain barrier dysfunction. Excessive circulating cytokines induces endothelial activation through receptors on cell surface including mIL‐6R, gp130, TNFR, and vascular endothelial growth factor receptor (VEGFR). Activated endothelial cell (EC) produces additional IL‐6 that forms positive feedback. Endothelial activation causes leakage with open tight junctions, which exposes pericyte at basement membrane to cytokines such as IFN‐γ to produces more IL‐6 and VEGF that exacerbate this process. EC may also be injured by damage associated molecular patterns (DAMPs) from tumor cell lysis. Endothelial leakage facilitates infiltration of peripheral chimeric antigen receptor T‐cell (CAR‐T) cell and cytokines into the central nervous system (CNS), and causes astrocyte endfoot process disruption with decreased fluid control and induces further cerebral edema.