In addition to the early vasogenic edema resulting from severe brain injury, the neurotoxic and metabolic sequelae of TBI leads to a disruption of cellular ionic homeostasis. Consequently, this disturbance in ionic equilibrium results in an increase of cellular volume and ICP rise which lead to reduce cerebral perfusion, neuronal injury and death in cases of refractory ICP. Mitochondrial dysfunction prevents the restoration of ionic and cellular volume homeostasis thereby exacerbating brain swelling. We will utilize magnetic resonance predominantly cellular and measure the amount of total water increase by our established water mapping methods. Studies of barrier permeability will elucidate the evolution of edematous process. Secondly, as we posit that traumatic brain injury leads to loss of membrane integrity, mitochondrial dysfunction and subsequent neuronal injury, we will utilize proton spectroscopy to gauge the reduction of N-Acetyl-Aspartate (NAA) as a reduced NAA is caused by early ischemia. Finally, as NAA is synthesized by the mitochondria, we will determine the neuroprotective effect of Cyclosporin A and increased oxygenation in ameliorating ionic disruption and subsequent brain swelling thus providing new information relevant to the more rational management of the head injured patient.
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