Fig. 10

Schematic image shows the involvement of S100B/RAGE-enhanced ADAM17 activation in the development of traumatic brain injury. At the onset of TBI, the upregulation of S100B in astrocytes are rapidly released and accumulates in extracellular space, which could exert its effect back on astrocytes through paracrine, and on endothelial cells through systemic circulation. The binding of S100B with its receptor RAGE stimulates astrocytes to further enhance the synthesis and secretion of S100B. Then, the activation of S100B/RAGE signal and its specific up-regulation on ADAM17 promotes the shedding of endothelial glycocalyx, aggravates the dysfunction of BBB, and increases the vascular permeability, leading to secondary brain and lung injury, or even multiple organ dysfunction syndromes (MODS)