Figure 1.

Diagnostic criteria, symptoms and immune cell involvement in moderate to severe traumatic Brain Injury (TBI) in comparison with mild TBI. Commonly used diagnostic criteria in moderate to severe TBI compared to mild TBI shows the major clinical difference between the two reflects hemorrhage or clear contusion in the brain. Symptoms are shared across mild, moderate and severe TBI with increasing likelihood of symptom occurrence and severity with increasing injury. Schematics represent immune response in moderate to severe TBI (left) and mild TBI (right). In moderate to severe TBI in humans and animal models, there is clear evidence for resident microglia activation and recruitment of macrophages, dendritic cells, neutrophils, B cells and T cells, and meningeal inflammation. In addition to active recruitment mechanisms, peripheral immune cells can infiltrate with frank hemorrhage alongside red blood cells (RBCs) and the release of hemoglobin (Hgb), Haem, and other damage associated molecular patterns (DAMPs), which are one set of initiators of the immune response. In contrast, in mild TBI there is little evidence of infiltrating immune cells to the brain tissue in humans or animal models that do not produce hemorrhage or skull opening. In mild TBI, there is evidence of meningeal inflammation, microglial activation, and some monocyte/macrophage recruitment to the cerebrovasculature.