Diffuse axonal injury (DAI) in the white matter of the cerebral hemispheres and brainstem, and combinations of brain swelling and ischemia, appear to be the principal cause of death and disability after head injury. Based on studies of cerebral blood flow using 133-Xenon IV techniques and measurements of cerebral 02 metabolism (CMR02) we now have evidence that hyperventilation increases CMR02 in comatose patients and, since metabolic acidosis is a common finding in acute head injury patients, hyperventilation may create a more favorable environment for cerebral metabolic processes in the comatose patient. We have also established the importance of CBF and CMR02 in the acute phase of head injury for subsequent outcomes. Analysis of data from our model of nonimpact acceleration injury in the rhesus monkey and baboon has provided evidence that the head has a profound directional sensitivity to damage induced by angular acceleration. Also, we have found that the pathophysiological mechanisms of DAI and gliding contusions may be similar. We have developed a model of axonal injury in the guinea pig optic nerve and initial evidence indicates that such injury has the same morphology as that produced by DAI in whole primate brains and in humans. We now have evidence that there are marked increases in intracellular calcium ion concentration after stretch injuries in the squid giant axon which appear to be related to recovery. Ischemic injury to the subiculum and anterior dentate may be caused by additional lactic acid derived from glucose in the CSF of the adjacent 3rd ventricle. Using 31P and 1H NMR techniques we have evidence that threshold ischemia, as indicated by increased lactate and phosphocreatine levels, occurs at perfusion pressures of 10-20mm Hg. Finally, we have begun a new set of NMR experiments to quantitatively measure rCBF from clearance curves of flourine containing compounds. Initial results are very encouraging. The clearance curves are biexponential and look very much like 133- Xenon clearance curves.

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