Figure 1.

A conceptualized framework of brain injury, cross-linking subfields of neuroscience, nutrition, and environmental toxicology. (A) Biomechanical force causes tissue damage (primary injury) and initiates neuroimmune response. Secondary injury, with a characteristic cascade of neurochemical events, occurs from the point of primary injury and continues for days, weeks, or months. Over the course of injury, the neuroimmune response goes from fully activated, to an immune dampening state, to finally a return to resting state. (B) Altered microbiome/increased circulating lipopolysaccharide (LPS) is hypothesized to be the primary injury, which activates the neuroimmune response, including the classic secondary injury features and neurochemical events as seen with conventional brain trauma. It is conjectured that this type of injury is most associated with chronic, subclinical neuroimmune activation.