The central theme of this proposal is to identify the metabolic destination of cerebral glucose taken up after traumatic brain injury (TBI), thereby discovering alternative metabolic pathways receptive to interventions (metabolic therapy) to enhance cellular and functional recovery and ultimately change the future of TBI patient management. Two basic science projects will explore these fundamental issues, and are designed to lead as well as complement two clinical projects. Project 1 (Dr. Richard Sutton) addresses the administration of glucose and pyruvate following cortical controlled impact in the rat to examine their impact on cerebral metabolism, cellular protection and outcome. Project 2 (Dr. Mayumi Prins) will study postnatal day 35 and postnatal day 90 rats using the developmental maturation of fuel transporters as an independent variable. Transporters for the fuels glucose, lactate and ketones will be measured in terms of their expression and function. The focus of ketone metabolism is a unique feature in this project as it not only addresses the effect on outcome, but also rigorously studies the appropriate biochemical pathways. Project 3 (Dr. Paul Vespa) addresses the topic of glucose substrate supply for human TBI patients primarily from the perspective of management of serum glucose concentration. Using different levels of insulin therapy, the effect on global and regional cerebral metabolism will be compared to neurochemical and anatomical markers of cell distress. In a creative cross over experimental design preliminary data will be collected for a future clinical trail. Project 4 (Dr. Neil Martin) will utilize the Kety-Schmidt technique to address how glucose is consumed differently in the human injured brain. The investigators within this program will determine the change in the consumption of cerebral glucose, the effects of changes in transporters, and the effects of enhancing or restricting glucose delivery and the potential use of alternative fuels. This program project will be housed within the UCLA Brain Injury Research Center (Dr. David A. Hovda, Director) so as to assure appropriate imaging, administrative and laboratory support.

Public Health Relevance

The critical care of traumatic brain injured patients in the intensive care unit currently relies on potentially inaccurate information regarding the role of glucose in cerebral metabolism. Patient care may be currently directed under the wrong assumptions, creating a false sense of security regarding the attempt to protect the brain from secondary insults. Our proposed studies are essential to understand the conditions that would enable appropriate metabolic therapy to be applied during the acute period after injury as well as remove potentially harmful interventions or treatment practices.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Program Projects (P01)
Project #
Application #
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Hicks, Ramona R
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Los Angeles
Schools of Medicine
Los Angeles
United States
Zip Code
Wardak, Mirwais; Schiepers, Christiaan; Cloughesy, Timothy F et al. (2014) ¹?F-FLT ???and ¹?F-FDOPA PET kinetics in recurrent brain tumors. Eur J Nucl Med Mol Imaging 41:1199-209
Hirata, Kenji; Kobayashi, Kentaro; Wong, Koon-Pong et al. (2014) A semi-automated technique determining the liver standardized uptake value reference for tumor delineation in FDG PET-CT. PLoS One 9:e105682
Hovda, David A (2014) The neurophysiology of concussion. Prog Neurol Surg 28:28-37
Irimia, A; Goh, S Y; Torgerson, C M et al. (2014) Structural and connectomic neuroimaging for the personalized study of longitudinal alterations in cortical shape, thickness and connectivity after traumatic brain injury. J Neurosurg Sci 58:129-44
Greco, Tiffany; Prins, Mayumi L (2013) Traumatic brain injury and diet. J Child Neurol 28:983-8
Glenn, Thomas C; Hirt, Daniel; Mendez, Gustavo et al. (2013) Metabolomic analysis of cerebral spinal fluid from patients with severe brain injury. Acta Neurochir Suppl 118:115-9
Wu, Hsiao-Ming; Huang, Sung-Cheng; Vespa, Paul et al. (2013) Redefining the pericontusional penumbra following traumatic brain injury: evidence of deteriorating metabolic derangements based on positron emission tomography. J Neurotrauma 30:352-60
Arndt, Daniel H; Lerner, Jason T; Matsumoto, Joyce H et al. (2013) Subclinical early posttraumatic seizures detected by continuous EEG monitoring in a consecutive pediatric cohort. Epilepsia 54:1780-8
Prins, Mayumi; Greco, Tiffany; Alexander, Daya et al. (2013) The pathophysiology of traumatic brain injury at a glance. Dis Model Mech 6:1307-15
Irimia, Andrei; Goh, S-Y Matthew; Torgerson, Carinna M et al. (2013) Electroencephalographic inverse localization of brain activity in acute traumatic brain injury as a guide to surgery, monitoring and treatment. Clin Neurol Neurosurg 115:2159-65

Showing the most recent 10 out of 24 publications