Guilty Molecules, Guilty Minds? The Conflicting Roles of the Innate Immune Response to Traumatic Brain Injury

Figure 1

Passage of innate immune components through the blood brain barrier (BBB) after TBI. Injury to the brain results in transient opening of the BBB, in which complement proteins and neutrophils are able to directly enter the parenchyma. Peripheral monocytes enter the brain through a process of extravasation, in which several adhesion molecules are upregulated in turn on both the monocyte and endothelial cell to first tether, then provide passage for the cell through the BBB. First, constitutively expressed L-selectin binds to upregulated P/E-selectin on the endothelial cell surface. Once tethered to the endothelium, monocytes are exposed to chemokines that bind to their cognate receptors on the cell, inducing conformational change and upregulation of β2 integrins, which bind to ICAMs expressed on endothelial cells. This final interaction between adhesion molecules signals the cell to migrate across the endothelium into the parenchyma, where it begins to differentiate and take on the morphology of an activated macrophage. Under the influence of chemokines, the cell continues the transition to an activated macrophage state migrates to the site of injury. Figure adapted from [51].