TBI-Induced Cerebral Metabolic Depression and Recovery

Summary

Principal Investigator: David A Hovda
Abstract: 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.
Funding Period: 2009-04-01 - 2015-03-31
more information: NIH RePORT

Top Publications

  1. pmc Metabolic and histologic effects of sodium pyruvate treatment in the rat after cortical contusion injury
    Masamichi Fukushima
    Brain Injury Research Center, David Geffen School of Medicine at UCLA, Los Angeles, California 90095 7039, USA
    J Neurotrauma 26:1095-110. 2009
  2. ncbi Early cerebral metabolic crisis after TBI influences outcome despite adequate hemodynamic resuscitation
    Nathan R Stein
    Department of Neurosurgery, David Geffen School of Medicine at UCLA, 757 Westwood Blvd, RR 6236A, Los Angeles, CA 90095, USA
    Neurocrit Care 17:49-57. 2012
  3. ncbi Tight glycemic control increases metabolic distress in traumatic brain injury: a randomized controlled within-subjects trial
    Paul Vespa
    Department of Neurology, UCLA School of Medicine, Los Angeles, CA, USA
    Crit Care Med 40:1923-9. 2012
  4. ncbi A pediatric perspective on concussion pathophysiology
    Meeryo C Choe
    Department of Pediatrics, Division of Pediatric Neurology, David Geffen School of Medicine and Mattel Children s Hospital at UCLA, California 90095 1752, USA
    Curr Opin Pediatr 24:689-95. 2012
  5. pmc Redefining the pericontusional penumbra following traumatic brain injury: evidence of deteriorating metabolic derangements based on positron emission tomography
    Hsiao Ming Wu
    Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 7039, USA
    J Neurotrauma 30:352-60. 2013
  6. ncbi Metabolomic analysis of cerebral spinal fluid from patients with severe brain injury
    Thomas C Glenn
    Department of Neurosurgery, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095 7039, USA
    Acta Neurochir Suppl 118:115-9. 2013
  7. pmc Early metabolic crisis-related brain atrophy and cognition in traumatic brain injury
    Matthew J Wright
    Los Angeles Biomedical Research Institute, Psychology Division, Department of Psychiatry, Harbor University of California, Los Angeles Medical Center, 1124 W Carson St, B 4 South Box 490, Torrance, CA, 90502, USA
    Brain Imaging Behav 7:307-15. 2013
  8. ncbi Traumatic brain injury and diet
    Tiffany Greco
    Department of Neurosurgery, UCLA Brain Injury Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 7039, USA
    J Child Neurol 28:983-8. 2013
  9. pmc Forward and inverse electroencephalographic modeling in health and in acute traumatic brain injury
    Andrei Irimia
    Laboratory of Neuro Imaging, Department of Neurology, University of California, Los Angeles, CA 90095, USA
    Clin Neurophysiol 124:2129-45. 2013
  10. pmc The effects of repeat traumatic brain injury on the pituitary in adolescent rats
    Tiffany Greco
    1 Department of Neurosurgery, Semel Institute, Los Angeles, California
    J Neurotrauma 30:1983-90. 2013

Research Grants

Detail Information

Publications30

  1. pmc Metabolic and histologic effects of sodium pyruvate treatment in the rat after cortical contusion injury
    Masamichi Fukushima
    Brain Injury Research Center, David Geffen School of Medicine at UCLA, Los Angeles, California 90095 7039, USA
    J Neurotrauma 26:1095-110. 2009
    ..Enduring (2 week) neuronal protection was achieved only with multiple SP treatments within the first 2 h post-CCI, perhaps reflecting the need for additional fuel throughout the acute period of increased metabolic demands induced by CCI...
  2. ncbi Early cerebral metabolic crisis after TBI influences outcome despite adequate hemodynamic resuscitation
    Nathan R Stein
    Department of Neurosurgery, David Geffen School of Medicine at UCLA, 757 Westwood Blvd, RR 6236A, Los Angeles, CA 90095, USA
    Neurocrit Care 17:49-57. 2012
    ..Optimal resuscitation after traumatic brain injury (TBI) remains uncertain. We hypothesize that cerebral metabolic crisis is frequent despite adequate resuscitation of the TBI patient and that metabolic crisis negatively influences outcome...
  3. ncbi Tight glycemic control increases metabolic distress in traumatic brain injury: a randomized controlled within-subjects trial
    Paul Vespa
    Department of Neurology, UCLA School of Medicine, Los Angeles, CA, USA
    Crit Care Med 40:1923-9. 2012
    ..To determine the effects of tight glycemic control on brain metabolism after traumatic brain injury using brain positron emission tomography and microdialysis...
  4. ncbi A pediatric perspective on concussion pathophysiology
    Meeryo C Choe
    Department of Pediatrics, Division of Pediatric Neurology, David Geffen School of Medicine and Mattel Children s Hospital at UCLA, California 90095 1752, USA
    Curr Opin Pediatr 24:689-95. 2012
    ..Recent literature detailing the pathophysiology of mild TBI (mTBI), with attention to pediatric studies, is presented...
  5. pmc Redefining the pericontusional penumbra following traumatic brain injury: evidence of deteriorating metabolic derangements based on positron emission tomography
    Hsiao Ming Wu
    Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 7039, USA
    J Neurotrauma 30:352-60. 2013
    ..68) with time after injury. A large proportion (%area: 22-76%) of pericontusional hypodense GM tissue had CMRO2 values less than 35 μmol/100 g/min, with this percentage increased with time after injury...
  6. ncbi Metabolomic analysis of cerebral spinal fluid from patients with severe brain injury
    Thomas C Glenn
    Department of Neurosurgery, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095 7039, USA
    Acta Neurochir Suppl 118:115-9. 2013
    ..By analyzing the CSF of patients with TBI, our goal was to create a metabolomic fingerprint for brain injury...
  7. pmc Early metabolic crisis-related brain atrophy and cognition in traumatic brain injury
    Matthew J Wright
    Los Angeles Biomedical Research Institute, Psychology Division, Department of Psychiatry, Harbor University of California, Los Angeles Medical Center, 1124 W Carson St, B 4 South Box 490, Torrance, CA, 90502, USA
    Brain Imaging Behav 7:307-15. 2013
    ..Our findings suggest that interventions that reduce acute metabolic crisis may lead to improved functional outcomes for traumatic brain injury survivors...
  8. ncbi Traumatic brain injury and diet
    Tiffany Greco
    Department of Neurosurgery, UCLA Brain Injury Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 7039, USA
    J Child Neurol 28:983-8. 2013
    ..Despite this knowledge, defining optimal nutritional support following traumatic brain injury continues to be an ongoing challenge. ..
  9. pmc Forward and inverse electroencephalographic modeling in health and in acute traumatic brain injury
    Andrei Irimia
    Laboratory of Neuro Imaging, Department of Neurology, University of California, Los Angeles, CA 90095, USA
    Clin Neurophysiol 124:2129-45. 2013
    ..EEG source localization is demonstrated in three cases of acute traumatic brain injury (TBI) with progressive lesion loads using anatomically faithful models of the head which account for pathology...
  10. pmc The effects of repeat traumatic brain injury on the pituitary in adolescent rats
    Tiffany Greco
    1 Department of Neurosurgery, Semel Institute, Los Angeles, California
    J Neurotrauma 30:1983-90. 2013
    ..RTBI causes significant disruption of the GH/IGF-1 axis that may ultimately affect normal cognitive and physical development during adolescence...
  11. pmc Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury
    Nobuhiro Moro
    UCLA Brain Injury Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 7039, USA Department of Neurosurgery, David Geffen School of Medicine at UCLA, Box 957039, Los Angeles, CA 90095 7039, USA Electronic address
    Brain Res 1535:124-36. 2013
    ....
  12. pmc Electroencephalographic inverse localization of brain activity in acute traumatic brain injury as a guide to surgery, monitoring and treatment
    Andrei Irimia
    The Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Los Angeles, USA
    Clin Neurol Neurosurg 115:2159-65. 2013
    ..To inverse-localize epileptiform cortical electrical activity recorded from severe traumatic brain injury (TBI) patients using electroencephalography (EEG)...
  13. ncbi Subclinical early posttraumatic seizures detected by continuous EEG monitoring in a consecutive pediatric cohort
    Daniel H Arndt
    Department of Pediatrics and Adult Neurology, Beaumont Children s Hospital, Oakland University, Royal Oak, Michigan, U S A
    Epilepsia 54:1780-8. 2013
    ..Continuous video-EEG monitoring (cEEG) was utilized to assess the burden of clinical and electrographic EPTS...
  14. pmc The pathophysiology of traumatic brain injury at a glance
    Mayumi Prins
    Department of Neurosurgery, UCLA, Los Angeles, CA 90095, USA
    Dis Model Mech 6:1307-15. 2013
    ..Recognition of these recurrent features could allow elucidation of potential therapeutic targets for early intervention. ..
  15. ncbi The linear relationship between transcranial Doppler pulsatility indices and intracranial pressure is influenced by traumatic brain injury and vasospasm
    Thomas C Glenn
    Department of Neurosurgery, University of California, Los Angeles, CA, USA
    Acta Neurochir Suppl 114:11-5. 2012
    ..We conclude that the fundamental relationship of PI to ICP is weakly positive at best...
  16. pmc Concussive brain injury enhances fear learning and excitatory processes in the amygdala
    Maxine L Reger
    UCLA Neurotrauma Laboratory, Department of Neurosurgery, David Geffen School of Medicine, University of California at Los Angeles, CA 90095, USA
    Biol Psychiatry 71:335-43. 2012
    ..However, because physically traumatic events typically occur in a highly emotional context, it is unknown whether traumatic brain injury itself is a cause of augmented fear and anxiety...
  17. pmc Acute neuroprotection to pilocarpine-induced seizures is not sustained after traumatic brain injury in the developing rat
    G G Gurkoff
    Department of Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, 10833 Le Conte Avenue, 18 228 Semel Institute, Los Angeles, CA 90095 7039, USA
    Neuroscience 164:862-76. 2009
    ....
  18. pmc Intracranial pressure pulse morphological features improved detection of decreased cerebral blood flow
    Xiao Hu
    Department of Neurosurgery, The David Geffen School of Medicine, Neural Systems and Dynamics Laboratory, University of California, Los Angeles, CA, USA
    Physiol Meas 31:679-95. 2010
    ..This study demonstrated that the potential role of ICP monitoring may be extended to provide an indicator of low global cerebral blood perfusion...
  19. pmc Beneficial effects of sodium or ethyl pyruvate after traumatic brain injury in the rat
    Nobuhiro Moro
    Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
    Exp Neurol 225:391-401. 2010
    ..Thus, delayed pyruvate treatments after CCI are neuroprotective and improve neurobehavioral recovery; these effects may be mediated by improved metabolism and reduced inflammation...
  20. pmc Nonconvulsive seizures after traumatic brain injury are associated with hippocampal atrophy
    P M Vespa
    UCLA Department of Neurosurgery, Los Angeles, CA 90095, USA
    Neurology 75:792-8. 2010
    ..To determine if posttraumatic nonconvulsive electrographic seizures result in long-term brain atrophy...
  21. pmc Repeat traumatic brain injury in the juvenile rat is associated with increased axonal injury and cognitive impairments
    M L Prins
    Department of Neurosurgery, UCLA David Geffen School of Medicine, Los Angeles, Calif, USA
    Dev Neurosci 32:510-8. 2010
    ..This study marks the first critical step in experimentally addressing the consequences of concussions and the cumulative effects of RTBI in the developing brain...
  22. pmc Astrocyte oxidative metabolism and metabolite trafficking after fluid percussion brain injury in adult rats
    Brenda L Bartnik-Olson
    Brain Injury Research Center, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA
    J Neurotrauma 27:2191-202. 2010
    ....
  23. pmc Molecular and physiological responses to juvenile traumatic brain injury: focus on growth and metabolism
    Talin Babikian
    Department of Psychiatry, David Geffen School of Medicine at UCLA, Los Angeles, Calif, USA
    Dev Neurosci 32:431-41. 2010
    ....
  24. ncbi The molecular pathophysiology of concussive brain injury
    Garni Barkhoudarian
    Department of Neurosurgery, David Geffen School of Medicine at UCLA, 10833 Le Conte Boulevard, Los Angeles, CA 90095, USA
    Clin Sports Med 30:33-48, vii-iii. 2011
    ..These biomarkers (eg, laboratory tests, imaging, electrophysiology) will then allow for improved detection, better functional assessment and evidence-based return to play recommendations...
  25. pmc Delayed sodium pyruvate treatment improves working memory following experimental traumatic brain injury
    Nobuhiro Moro
    Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA 90095, USA
    Neurosci Lett 491:158-62. 2011
    ..These results show that spatial alternation testing can reliably detect temporal deficits and recovery of working memory after TBI and that delayed pyruvate treatment can ameliorate TBI-induced cognitive impairments...
  26. pmc Quantitative proton magnetic resonance spectroscopy and spectroscopic imaging of the brain: a didactic review
    Jeffry R Alger
    Department of Neurology, Ahmanson Lovelace Brain Mapping Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 7085, USA
    Top Magn Reson Imaging 21:115-28. 2010
    ..Current approaches to obtaining accurate amplitude estimates with least-squares fitting software are summarized...
  27. pmc Ketogenic diet prevents alterations in brain metabolism in young but not adult rats after traumatic brain injury
    Ying Deng-Bryant
    Department of Neurosurgery, UCLA David Geffen School of Medicine, Los Angeles, California, USA
    J Neurotrauma 28:1813-25. 2011
    ..Moreover, the younger brains revert to ketones metabolism more quickly than do the adult brains, resulting in better neurochemical and cerebral metabolic recovery after injury...
  28. pmc Comparison of acute and chronic traumatic brain injury using semi-automatic multimodal segmentation of MR volumes
    Andrei Irimia
    Laboratory of Neuro Imaging, University of California, Los Angeles, California 90095, USA
    J Neurotrauma 28:2287-306. 2011
    ..With knowledge of general location, extent, and degree of change, such metrics can be associated with clinical measures and subsequently used to suggest viable treatment options...
  29. pmc Cerebral ketone metabolism during development and injury
    Mayumi L Prins
    Department of Neurosurgery, UCLA Brain Injury Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 7039, USA
    Epilepsy Res 100:218-23. 2012
    ....
  30. pmc ¹⁸F-FLT    and ¹⁸F-FDOPA PET kinetics in recurrent brain tumors
    Mirwais Wardak
    Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA, 90095 6948, USA
    Eur J Nucl Med Mol Imaging 41:1199-209. 2014
    ....

Research Grants30

  1. CENTER FOR GASTROINTESTINAL BIOLOGY AND DISEASE
    Robert S Sandler; Fiscal Year: 2013
    ..Through all of its activities, the Center improves communication, promotes collaboration, develops careers and generally enriches the intellectual climate for digestive disease research. ..
  2. Molecular Mechanisms linking Aging, Abeta Proteotoxicity and Neurodegeneration
    Jeffery W Kelly; Fiscal Year: 2013
    ..abstract_text> ..
  3. Emory Alzheimer's Disease Center
    Allan I Levey; Fiscal Year: 2013
    ..abstract_text> ..