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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
5P50NS012587-26
Application #
6651788
Study Section
Project Start
2002-09-01
Project End
2003-08-31
Budget Start
Budget End
Support Year
26
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Type
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
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Mazzeo, Anna Teresa; Alves, Oscar Luis; Gilman, Charlotte B et al. (2008) Brain metabolic and hemodynamic effects of cyclosporin A after human severe traumatic brain injury: a microdialysis study. Acta Neurochir (Wien) 150:1019-31;discussion 1031
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