Biochemical Markers of Traumatic Brain Injury

Summary

Principal Investigator: STEVEN ANDREW ROBICSEK
Abstract: DESCRIPTION (provided by applicant): Traumatic brain injury (TBI) is a major national health problem. There are currently no effective therapies for TBI. Biochemical markers could provide confirmation of injury mechanism(s) and identify drug therapy targets. Temporal profiles of changes in biomarkers could guide timing of treatment. Biomarkers could provide clinical trial outcome measures obtainable more readily than neurological assessments. Biomarkers could also provide more acurate early diagnosis and prognosis, as well as provide end points for improving patient management in acute care and intensive care environments. There are no FDA approved biochemical markers for TBI. This proposal would initiate the first systematic identification and validation of a panel of biochemical markers for TBI detectable in human cerebrospinal fluid (CSF), a biological fluid routinely accessible following severe TBI. Specific Aim 1 will assess the diagnostic and prognostic utility of candidate biomarkers (breakdown products to alpha-spectrin-SBDPs;UCH-L1;MAP2a/b;myelin basic protein-MBP;S100B) by examining relationships between levels of specific biomarkers and injury magnitude (e.g. Glasgow Coma Scale-GCS), injury type (e.g. diffuse injury vs. mass lesion), occurrence of secondary insults (e.g. hypotension, elevated intracranial pressure) and outcome (e.g. neurological assessments and MRI). Sensitivity and specificity of markers, alone and in combination will be determined. Specific Aim 2 will assess the utility of SBDPs for assessment of oncotic and apoptotic celldeath by examining relationships between CSF levels of SBDPs and specific pathological events that occur after TBI. Specific Aim 3 will prospectively validate in a separate group of patients a diagnostic/prognostic panel of biomarkers selected on the basis of data from Specific Aim 1 by determining if the biomarker information will add diagnostic/prognostic information to the clinical data that is currently available and the information provided by individual biomarkers.
Funding Period: ----------------2006 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. ncbi Alpha-II-spectrin after controlled cortical impact in the immature rat brain
    J Aikman
    Center for Traumatic Brain Injury Studies, Evelyn F and William L McKnight Brain Institute of the University of Florida, Gainesville, FL, USA
    Dev Neurosci 28:457-65. 2006
  2. ncbi Increased levels of serum MAP-2 at 6-months correlate with improved outcome in survivors of severe traumatic brain injury
    Stefania Mondello
    University of Florida, Department of Anesthesiology, Gainesville, FL, USA
    Brain Inj 26:1629-35. 2012
  3. pmc Human traumatic brain injury induces autoantibody response against glial fibrillary acidic protein and its breakdown products
    Zhiqun Zhang
    Banyan Biomarkers Inc, Alachua, Florida, United States of America
    PLoS ONE 9:e92698. 2014
  4. pmc Ubiquitin C-terminal hydrolase is a novel biomarker in humans for severe traumatic brain injury
    Linda Papa
    Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, FL, USA
    Crit Care Med 38:138-44. 2010
  5. ncbi Clinical significance of alphaII-spectrin breakdown products in cerebrospinal fluid after severe traumatic brain injury
    Jose A Pineda
    Center for Traumatic Brain Injury Studies, E F and W L McKnight Brain Institute of the University of Florida, Gainesville, Florida, USA
    J Neurotrauma 24:354-66. 2007
  6. pmc A geometric flow-based approach for diffusion tensor image segmentation
    Weihong Guo
    Department of Mathematics, University of Alabama, Box 870350, Tuscaloosa, AL 35487, USA
    Philos Trans A Math Phys Eng Sci 366:2279-92. 2008
  7. pmc Methamphetamine- and trauma-induced brain injuries: comparative cellular and molecular neurobiological substrates
    Mark S Gold
    Center for Neuroproteomics and Biomarkers Research, McKnight Brain Institute of the University of Florida, Gainesville, Florida 32610, USA
    Biol Psychiatry 66:118-27. 2009
  8. pmc Brain injury biomarkers may improve the predictive power of the IMPACT outcome calculator
    Endre Czeiter
    Department of Neurosurgery, Medical School, University of Pecs, Pecs, Hungary
    J Neurotrauma 29:1770-8. 2012
  9. pmc Glial neuronal ratio: a novel index for differentiating injury type in patients with severe traumatic brain injury
    Stefania Mondello
    Department of Anesthesiology, University of Florida, Gainesville, Florida 32615, USA
    J Neurotrauma 29:1096-104. 2012
  10. pmc Serum concentrations of ubiquitin C-terminal hydrolase-L1 and αII-spectrin breakdown product 145 kDa correlate with outcome after pediatric TBI
    Rachel P Berger
    Children s Hospital of Pittsburgh of University of Pittsburgh Medical Center UPMC, Safar Center for Resuscitation Research, Pittsburgh, Pennsylvania 15224, USA
    J Neurotrauma 29:162-7. 2012

Scientific Experts

  • Gretchen M Brophy
  • Stefania Mondello
  • Rachel P Berger
  • Endre Czeiter
  • Kevin K W Wang
  • Mark S Gold
  • Claudia S Robertson
  • Linda Papa
  • Jose A Pineda
  • Zhiqun Zhang
  • Joseph J Tepas
  • Jason A Demery
  • H Julia Hannay
  • Ming Cheng Liu
  • Shelley C Heaton
  • Ronald L Hayes
  • Weihong Guo
  • J Aikman
  • STEVEN ROBICSEK
  • Jitendra R Dave
  • Zhihui Yang
  • Julia Hannay
  • Shelley Heaton
  • Boxuan Yang
  • Olena Glushakova
  • Richard Rubenstein
  • Firas Kobeissy
  • J Susie Zoltewicz
  • Kara Schmid
  • Frank Tortella
  • Joy Guingab
  • Kimberly J Newsom
  • Xi Chun May Lu
  • Andras Buki
  • Steven A Robicsek
  • Joe Layon
  • Gillian Robinson
  • Wenrong Zheng
  • Monika W Oli
  • Andrea Gabrielli
  • Linnet Akinyi
  • Irina N Krasnova
  • Lisa J Merlo
  • Firas H Kobeissy
  • Jean Lud Cadet
  • ADRIAAN W BRUIJNZEEL
  • Yunmei Chen
  • Qingguo Zeng
  • Alex B Valadka
  • Jada M Aikman
  • Stephen B Lewis
  • Veronica Akle
  • B O'Steen
  • J Pineda
  • K K W Wang
  • R Hayes
  • K Padgett
  • R Torres
  • S Boslaugh
  • X Silver
  • S Blackband

Detail Information

Publications15

  1. ncbi Alpha-II-spectrin after controlled cortical impact in the immature rat brain
    J Aikman
    Center for Traumatic Brain Injury Studies, Evelyn F and William L McKnight Brain Institute of the University of Florida, Gainesville, FL, USA
    Dev Neurosci 28:457-65. 2006
    ..Distinct proteolytic products resulting from the degradation of the cytoskeletal protein alpha-II-spectrin by calpain and caspase 3 were readily detectable in cortical brain parenchyma and cerebrospinal fluid after TBI in immature rats...
  2. ncbi Increased levels of serum MAP-2 at 6-months correlate with improved outcome in survivors of severe traumatic brain injury
    Stefania Mondello
    University of Florida, Department of Anesthesiology, Gainesville, FL, USA
    Brain Inj 26:1629-35. 2012
    ..To evaluate microtubule-associated proteins (MAP-2), a dendritic marker of both acute damage and chronic neuronal regeneration after injury, in serum of survivors after severe TBI and examine the association with long-term outcome...
  3. pmc Human traumatic brain injury induces autoantibody response against glial fibrillary acidic protein and its breakdown products
    Zhiqun Zhang
    Banyan Biomarkers Inc, Alachua, Florida, United States of America
    PLoS ONE 9:e92698. 2014
    ..Due to the long lasting nature of IgG, a test to detect anti-GFAP autoantibodies is likely to prolong the temporal window for assessment of brain damage in human patients. ..
  4. pmc Ubiquitin C-terminal hydrolase is a novel biomarker in humans for severe traumatic brain injury
    Linda Papa
    Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, FL, USA
    Crit Care Med 38:138-44. 2010
    ....
  5. ncbi Clinical significance of alphaII-spectrin breakdown products in cerebrospinal fluid after severe traumatic brain injury
    Jose A Pineda
    Center for Traumatic Brain Injury Studies, E F and W L McKnight Brain Institute of the University of Florida, Gainesville, Florida, USA
    J Neurotrauma 24:354-66. 2007
    ..Our data further suggests that both necrotic/oncotic and apoptotic cell death mechanisms are activated in humans following severe TBI, but with a different time course after injury...
  6. pmc A geometric flow-based approach for diffusion tensor image segmentation
    Weihong Guo
    Department of Mathematics, University of Alabama, Box 870350, Tuscaloosa, AL 35487, USA
    Philos Trans A Math Phys Eng Sci 366:2279-92. 2008
    ..We validate the proposed model and compare it with some other methods using synthetic and human brain DTI data; experimental results indicate that the proposed model improves the accuracy and efficiency in segmentation...
  7. pmc Methamphetamine- and trauma-induced brain injuries: comparative cellular and molecular neurobiological substrates
    Mark S Gold
    Center for Neuroproteomics and Biomarkers Research, McKnight Brain Institute of the University of Florida, Gainesville, Florida 32610, USA
    Biol Psychiatry 66:118-27. 2009
    ....
  8. pmc Brain injury biomarkers may improve the predictive power of the IMPACT outcome calculator
    Endre Czeiter
    Department of Neurosurgery, Medical School, University of Pecs, Pecs, Hungary
    J Neurotrauma 29:1770-8. 2012
    ..700. Our preliminary results underline the importance of biomarkers in outcome prediction, and encourage further investigation to expand the predictive power of contemporary outcome calculators and prognostic models in TBI...
  9. pmc Glial neuronal ratio: a novel index for differentiating injury type in patients with severe traumatic brain injury
    Stefania Mondello
    Department of Anesthesiology, University of Florida, Gainesville, Florida 32615, USA
    J Neurotrauma 29:1096-104. 2012
    ..In addition, GNR may help to identify different pathophysiological mechanisms following different types of brain trauma, with implications for therapeutic interventions...
  10. pmc Serum concentrations of ubiquitin C-terminal hydrolase-L1 and αII-spectrin breakdown product 145 kDa correlate with outcome after pediatric TBI
    Rachel P Berger
    Children s Hospital of Pittsburgh of University of Pittsburgh Medical Center UPMC, Safar Center for Resuscitation Research, Pittsburgh, Pennsylvania 15224, USA
    J Neurotrauma 29:162-7. 2012
    ..These results suggest that these two markers may be useful in assessing outcome after moderate and severe pediatric TBI...
  11. pmc Clinical utility of serum levels of ubiquitin C-terminal hydrolase as a biomarker for severe traumatic brain injury
    Stefania Mondello
    Department of Anesthesiology, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA
    Neurosurgery 70:666-75. 2012
    ..Brain damage markers released in cerebrospinal fluid (CSF) and blood may provide valuable information about diagnosis and outcome prediction after traumatic brain injury (TBI)...
  12. pmc Neuronal and glial markers are differently associated with computed tomography findings and outcome in patients with severe traumatic brain injury: a case control study
    Stefania Mondello
    Department of Anesthesiology, University of Florida, 1600 S, W, Archer Road, Gainesville, FL 32610 0254, USA
    Crit Care 15:R156. 2011
    ....
  13. pmc αII-spectrin breakdown products (SBDPs): diagnosis and outcome in severe traumatic brain injury patients
    Stefania Mondello
    Department of Clinical Programs and Center of Innovative Research, University of Florida, Gainesville, Florida, USA
    J Neurotrauma 27:1203-13. 2010
    ..The time course of SBDPs in nonsurvivors also differed from that of survivors. These results suggest that CSF SBDP levels can predict injury severity and mortality after severe TBI, and can be useful complements to clinical assessment...
  14. pmc alphaII-Spectrin breakdown product cerebrospinal fluid exposure metrics suggest differences in cellular injury mechanisms after severe traumatic brain injury
    Gretchen M Brophy
    Departments of Pharmacy and Neurosurgery, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, Virginia 23298 0533, USA
    J Neurotrauma 26:471-9. 2009
    ..Further studies are being conducted to determine if exposure and kinetic metrics for biofluid-based biomarkers can predict clinical outcome...
  15. pmc Biokinetic analysis of ubiquitin C-terminal hydrolase-L1 (UCH-L1) in severe traumatic brain injury patient biofluids
    Gretchen M Brophy
    Virginia Commonwealth University, Pharmacotherapy and Outcomes Sciences and Neurosurgery, Richmond, Virginia 23298 0533, USA
    J Neurotrauma 28:861-70. 2011
    ..This study shows a significant correlation between UCH-L1 CSF and serum median concentrations and biokinetics in severe TBI patients, and relationships with clinical outcome were detected...