Fig. 2

Cellular infiltration after TBI. a In healthy brain, the functional unit constituted by firmly coupled endothelial cells and astrocytic end-feet frame the blood-brain barrier (BBB). Immune cells flow unreservedly in the blood vessel, and in the brain parenchyma, blood-borne and brain-borne proteins cannot pass into the other compartment, resting microglia survey the intact brain ecosystem. b Following TBI, the BBB disrupted/leaked activating the endothelial cells. The tight junctions between endothelial cells perish. This allows immune cells to adhere at the blood vessels lamina and then transmigration to the brain parenchyma. Specific brain proteins (e.g. S100B) are released into the blood according to their concentration gradient in exchange, serum protein enters the brain parenchyma which has been demonstrated in the cartoon. Now, microglia switch from their resting state to an activated state, embracing a phagocytic phenotype and secreting pro-inflammatory proteins. Upregulation of adhesion molecules in cerebral vessels and production of chemokines by activated microglia and astrocytes finally cause blood leukocytes to migrate into the brain parenchyma where monocytes are suggested to cause additional damage to the brain