At present, there are no FDA-approved pharmacological therapies for acute treatment of traumatic brain injury (TBI) patients that are conclusively proven to mitigate the often devastating neurological effects of their injuries. Nevertheless, the possibility of an effective neuroprotective treatment is based upon the fact that even though some of the neural injury is due to the primary mechanical events (i.e., shearing of nerve cells and blood vessels), the majority of posttraumatic neurodegeneration is due to a pathomolecular and pathophysiological secondary cascade that occurs during the first minutes, hours and days following the injury which exacerbates the damaging effects of the primary injury. One of the most validated “secondary injury” mechanisms revealed in experimental TBI studies involves oxygen radical-induced
oxidative damage to brain cell lipids and proteins. This chapter outlines the key sources of reactive oxygen species (ROS) including highly reactive (i.e., rapidly oxidizing) free radicals, the mechanisms associated with their neural damage, pharmacological scavenging antioxidants that have been shown to produce neuroprotective effect in TBI models and brief mention of the most widely used methods for studying the extent of lipid and protein oxidative damage in TBI models.