Figure 6

Molecular pathogenesis of TBI and CTE. The upper left panel shows the typical sites of coup/contrecoup injury as occur in blast as well as other types of closed head injuries. The lower left panel illustrates the most common locations for diffuse axonal injury (pink) and contusions (blue) following closed head injuries. Reproduced with permission from Taber et al.[80]. The large panel on the right illustrates current concepts of mechanisms underlying primary and secondary injury mechanisms in TBI. At early times after injury, glutamate release and ionic disturbances (Na+, Ca2+ and K+) disrupt energy metabolism and cause other metabolic disturbances that lead to decreases in cerebral blood flow. Mitochondrial dysfunction causes increases in reactive oxygen (ROS) and nitrogen species (RNS) that can cause further cellular injury. Tissue damage evokes neuro-inflammatory changes that emerge later. Injury may be exacerbated by secondary clinical factors including hypoxemia, hypotension, fever and seizures. These secondary molecular and clinical factors lead to progressive tissue damage. Abbreviations: Ca2+, calcium ions; CPP, cerebral perfusion pressure; Glc, Glucose; ICP, intracranial pressure; K+, potassium; Na+, sodium; rCBF, regional cerebral blood flow. Reproduced from Marklund et al.[70] with permission.