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Project Title:
Identification of Biomarkers for inflicted traumatic brain injury using the human cerebrospinal fluid proteome
Funding Agency:
Centers for Disease Control
Total Project Period:
Sep 01, 2004 - Aug 31, 2006
Principal Investigator:
Weiman Gao, MD, PhD
Co-Investigator(s):
Patrick Kochanek, MD; Larry Jenkins, PhD; Rachel Berger, MD, MPH
Project Summary:
Inflicted traumatic brain injury (iTBI) – often referred to as shaken baby syndrome, is the most common cause of traumatic death in infancy. Like many other central nervous system (CNS) pathologies, iTBI results in changes in the composition of the cerebrospinal fluid (CSF). As a result, CSF offers a window into the basic molecular mechanisms of CNS injury after TBI. Changes in protein composition of CSF may be indicative of a prognostic, diagnostic,k or mechanistic pattern of CNS protein expression. Our research group at the Safar Center has led the way in the search for CSF and serum biomarkers of brain injury that might be able to aid clinicians in making the diagnosis of iTBI and in discriminating non-inflicted TBI (nTBI) from iTBI. These studies have demonstrated that patients with iTBI and nTBI have important differences in a number of biochemical markers. These differences appear to reflect, at least in part, a significant chronic component of injury in iTBI vs. nTBI and a possible role for hypoxia in the pathophysiology of iTBI.
The aim of this project is to identify potential protein patterns in CSF that may be able to help differentiate iTBI from nTBI using a novel approach that, to our knowledge, has never been used in this context. Proteomic analysis including two-dimensional (2-D) difference in gel electrophoresis (DIGE) combined with mass spectrometry analysis will be used to compare the CSF protein profile of iTBI and nTBI patients. Based on our preliminary data, this highly novel approach has a great potential to provide new insight into the pathophysiology of iTBI and to define a fingerprint of this type of injury.
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