Fig. 2.

Traumatic brain injury-induced macrophage response varies in reaction to immune stressors that occur before, with, and after the injury. A solid black line and gray shading depicts normal, age-related health burden. A) Traumatic brain injury (TBI) occurring in the absence of Aβ (dotted black line) or tau results in acute macrophage-related neuroinflammation that subsides over time. TBI in the presence of Aβ (solid red line) results in an acute blunted macrophage response that increases at chronic post-injury time points. TBI in the presence of pathological tau (solid blue line) results in an enhanced macrophage response to TBI that remains elevated at chronic post-injury time points. B) Over time, macrophage-related neuroinflammation increases with normal health burden. Single TBI (dotted black line) results in acute macrophage-related neuroinflammation that subsides over time. Pre-injury peripheral immune challenge at sub-threshold levels (red line) attenuates the post-injury macrophage-related inflammatory response to TBI. Post-injury peripheral immune challenge (solid blue line) causes a hyper-active macrophage response correlating with behavioral dysfunction. Repetitive post-injury immune challenge (dotted blue line), similar to what is observed in repetitive TBI, increases macrophage-related neuroinflammation and correlates with the advanced neuropathology. The figure represents a model of what occurs in human TBI, translating specific findings in rodent TBI studies. (Reproduced from Kokiko-Cochran ON, Godbout JP (2018) The inflammatory continuum of traumatic brain injury and Alzheimer’s disease. Front Immunol 9, 672.)