Abstract

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 Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS052831-04
Application #
7635835
Study Section
Clinical Neuroscience and Disease Study Section (CND)
Program Officer
Hicks, Ramona R
Project Start
2006-07-26
Project End
2011-04-30
Budget Start
2009-05-01
Budget End
2010-04-30
Support Year
4
Fiscal Year
2009
Total Cost
$976,160
Indirect Cost

  Institution

Name
University of Florida
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611

  Publications

Mondello, Stefania; Kobeissy, Firas; Vestri, Annarita et al. (2016) Serum Concentrations of Ubiquitin C-Terminal Hydrolase-L1 and Glial Fibrillary Acidic Protein after Pediatric Traumatic Brain Injury. Sci Rep 6:28203
Kobeissy, Firas H; Liu, Ming Cheng; Yang, Zhihui et al. (2015) Degradation of ?II-Spectrin Protein by Calpain-2 and Caspase-3 Under Neurotoxic and Traumatic Brain Injury Conditions. Mol Neurobiol 52:696-709
Tóth, Arnold; Schmalfuss, Ilona; Heaton, Shelley C et al. (2015) Lateral Ventricle Volume Asymmetry Predicts Midline Shift in Severe Traumatic Brain Injury. J Neurotrauma 32:1307-11
Zhang, Zhiqun; Zoltewicz, J Susie; Mondello, Stefania et al. (2014) Human traumatic brain injury induces autoantibody response against glial fibrillary acidic protein and its breakdown products. PLoS One 9:e92698
Mondello, Stefania; Gabrielli, Andrea; Catani, Sheila et al. (2012) Increased levels of serum MAP-2 at 6-months correlate with improved outcome in survivors of severe traumatic brain injury. Brain Inj 26:1629-35
Mondello, Stefania; Jeromin, Andreas; Buki, Andras et al. (2012) Glial neuronal ratio: a novel index for differentiating injury type in patients with severe traumatic brain injury. J Neurotrauma 29:1096-104
Zoltewicz, J Susie; Scharf, Dancia; Yang, Boxuan et al. (2012) Characterization of Antibodies that Detect Human GFAP after Traumatic Brain Injury. Biomark Insights 7:71-9
Mondello, Stefania; Linnet, Akinyi; Buki, Andras et al. (2012) Clinical utility of serum levels of ubiquitin C-terminal hydrolase as a biomarker for severe traumatic brain injury. Neurosurgery 70:666-75
Czeiter, Endre; Mondello, Stefania; Kovacs, Noemi et al. (2012) Brain injury biomarkers may improve the predictive power of the IMPACT outcome calculator. J Neurotrauma 29:1770-8
Berger, Rachel P; Hayes, Ronald L; Richichi, Rudolph et al. (2012) Serum concentrations of ubiquitin C-terminal hydrolase-L1 and ?II-spectrin breakdown product 145 kDa correlate with outcome after pediatric TBI. J Neurotrauma 29:162-7

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