Cerebral Lactate Metabolism Following Human Traumatic Brain Injury

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DESCRIPTION (provided by applicant): This project is focused on our recent demonstration that traumatic brain injury (TBI), after the first 12-24 hours, is typically accompanied by significant cerebral lactate uptake and utilization. This finding is not encompassed by contemporary concepts of post-traumatic cerebral metabolic dysfunction, and cannot easily be reconciled with the view that lactate accumulation and acidosis are common causes of cell death after trauma. Lactate is fundamental to the understanding of traumatic pathobiology. Furthermore, it is becoming a key component of neuro-monitoring through cerebral microdialysis; and it is regarded as an important marker of cerebral ischemia in arterio-jugular measurements, and MR spectroscopy. Because of the important yet incompletely understood role of lactate in metabolic dysfunction after TBI, we propose to study its uptake by the brain, and its metabolism. Our main hypothesis is that lactate is taken and oxidized in the brain after traumatic brain injury. We also intend to study cerebral glucose metabolism in an analogous and parallel fashion, to understand more completely the alterations in carbohydrate metabolism induced by injury. To answer the key scientific questions addressed in this project, we plan to take the novel approach of using deuterium (D2) and carbon (13C-)) glucose and lactate isotope tracer metabolic techniques to study cerebral metabolism in brain injury patients. Our specific aims are: 1. To determine the extent to which brain glucose uptake, glycolysis, and glucose oxidation are affected (suppressed) after TBI. 2. To determine the extent to which brain lactate uptake and oxidation are affected (augmented) after TBI. 3. To determine the extent to which the rates of lactate and glucose oxidation correlate with clinical characteristics and outcome after TBI. If the studies proposed in this project confirm that lactate is a viable fuel for the injured brain, the next step will be to consider lactate administration as "metabolic therapy" for brain injury. We have previously shown that the brain takes up the chemical called lactate after traumatic brain injury. This project will determine if the brain is using the lactate to help it recover after injury. If the studies proposed in this project confirm that lactate helps the injured brain, the next step will be to consider lactate administration as new "metabolic therapy" for brain injury.