TNF and myeloid sarcoma: While proinflammatory cytokines, such as tumor necrosis factor (TNF) α, interleukin (IL) -1β, interferon (IFN) γ and IL-17 released by circulating inflammatory cells, affect BBB integrity by directly disrupting tight junctions (IFNγ and IL-17), as well as by enhancing the activity of matrix metalloproteinase-9 (MMP-9) (IL-1β and TNFα) [70,71,72,73], EVs released from endothelial cells and platelets have been shown to increase endothelial permeability during MS [74] and to rapidly accumulate in the plasma of MS patients during disease relapses [75,76].