The principal objectives of this research are to determine the relative incidence and significance of mechanical and hypoxic brain damage in adults and children with severe head injuries and in a model of acceleration head injury in the rhesus monkey, using as criteria the neurological examination; measurements of intracranial pressure, cerebral blood flow, and metabolism; averaged evoked potentials; and neuropathology. Since we believe that hypoxic and ischemic hypoxia are common complications of head injury, we are also investigating in animals the sequence of events that leads to hypoxic brain damage at critical levels of cerebral perfusion pressure and systemic oxygenation, based on two hypotheses: 1) brain damge is not dependent on a failure of high energy phosphate metabolism; and 2) the weak link in persistent or irreversible hypoxic damage of the cell is failure of restoration of ion balance across the cell membrane. In the human studies, advantage is taken of the availability of non-invasive methods for anatomic localization of the lesion (CT scan) and assessment of regional cerebral blood flow (Xe133 inhalation method). Both of these new techniques permit serial observations during the course of the illness and on follow-up, which can be correlaed with outcome. When employed in conjunction with measurements of cerebral metabolic rate and intracranial pressure during the acute phase, information about the effectiveness of various therapies (e.g., mannitol and hyperventilation) can be evaluated. Parallel pathophysiologic studies are being carried out on the monkey, in whom head injuries of graded severity can be produced and better defined, and where a variety of experimental therapies can be tested.