Discovery of Novel Biomarkers for Brain Injury

This research proposal is based upon our preliminary studies demonstrating that the autoimmune response to traumatic brain injury (TBI) can serve as a pathway for the discovery of novel TBI biomarker proteins. Initially eleven brain proteins were identified as targeted by the autoimmune response to TBI. These proteins constitute the focus of the investigation proposed here. This investigation will first determine how TBI effects the expression of these candidate biomarkers in brain tissue. We expect that the expression profiles of our candidate proteins will reflect TBI status and thus, the potential value of each candidate as a blood-borne biomarker. Next we will validate the most promising candidate proteins as circulating biomarkers for TBI. In addition to identifying novel biomarkers for TBI, this research will determine how TBI affects the expression profiles of the biomarker proteins in brain and their respective autoantibodies in blood. This knowledge will provide insight into the pathologic mechanisms that underlie TBI and its long term sequelae including sleep disorders, epilepsy and post-traumatic stress disorder.

The central hypothesis for the proposed research is brain-specific autoantibodies can be used to identify proteins that will serve as circulating biomarkers for the assessment of TBI. The specific aims of the research are: (1) Determine the effects of TBI on the regional expression of candidate TBI biomarker proteins in rodent (rat) and human brain using immunohistochemistry, and (2) Validate in rodents and humans candidate proteins as blood-borne biomarkers for TBI using highly sensitive enzyme-linked immunosorbant assays and western blot analyses. This research will be carried out in both male and females to identify the affects of gender on the autoantibody and biomarker protein responses to TBI. This research will also better establish the scientific validity of the rodent as a model for investigating human TBI. This is essential for interpreting new findings derived from controlled experiments conducted in rodents. Finally, the knowledge gained from this research will contribute to the ultimate creation of a TBI biomarker chip that will be useful in assessing both the biomarker protein and autoantibody responses to TBI in humans.

Final report is available on NTRL at: https://ntrl.ntis.gov/NTRL/dashboard/searchResults/titleDetail/PB2014108875.xhtml