Pediatric traumatic brain injury (TBI) is a ?silent epidemic? affecting over 500,000 children each year. Metabolic crisis due to impaired oxidative glucose metabolism is a hallmark of TBI. Metabolism is indispensable for proper brain development and function, however, metabolic demands superimposed by trauma during these crucial periods of brain development result in secondary injury and further impaired neurological function. Emergent evidence and our preliminary data show that brain is capable of oxidizing fatty acids via mitochondrial ?-oxidation and this process is developmentally regulated. Our preliminary data show, that while brain glucose metabolism is decreased following TBI, fatty acid oxidation is increased in the injured brain. Our hypothesis is that pharmacological or genetic up-regulation of brain's fatty acids oxidation is a critical metabolic and neuroprotective target, which can support brain energy and metabolism during metabolic crisis. Using pediatric model of severe brain injury, we aim to test this hypothesis and determine the extent to which fatty acid oxidation may support oxidative metabolism after TBI. Therefore, we propose to: 1) quantify brain temporal and regional abilities to oxidize fatty acid after TBI; 2) determine that pharmacological or genetic increase of fatty acid oxidation will result in improved bioenergetics after TBI; 3) establish that improved neurological function and decreased extent of injury are due to increased metabolic support via increased fatty acid oxidation. To address this important, but still unanswered question, we will use multi-disciplinary approach and combine biochemical, genetic, behavioral and histological techniques.
The aim of this research to decipher brain's innate attempts to meet metabolic demands after the injury and pharmacologically amplify them towards meaningful improvement of neurological recovery and activities of daily life.

Public Health Relevance

Traumatic brain injury (TBI) in children causes life-long impairments in attention, learning and memory because the injury is superimposed on growing and developing brain. The brain's efficient use of glucose to fuel energy production and maintain all brain's activities is damaged after TBI. The proposed research is relevant to public health because it will help determine the extent to which the brain can also use fatty acids for energy and healing. Once this can be determined, new therapeutic approaches for healing the damaged brain can be developed. Thus, the proposed research is relevant to NINDS's mission to reduce the burden of neurological injury, and is intended to support functional recovery and better quality of life for both children and adults with TBI. !

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Acute Neural Injury and Epilepsy Study Section (ANIE)
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Bambrick, Linda Louise
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Johns Hopkins University
Schools of Medicine
United States
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