EVALUATION OF CLINICALLY RELEVANT PROGNOSTIC INDICATORS IN A MODEL OF MILD TBI/CONCUSSION

At least 75% of civilian traumatic brain injuries are mild (mTBI), and in Soldiers returning from Operation Enduring Freedom and Operation Iraqi Freedom, 44% of all TBIs were mild. About 20% of patients continue to suffer from post-concussion symptoms for at least a year or more post-injury. The lack of good prognostic indicators for the early identification of mTBI patients who will later have long-term deficits has been identified as a primary research gap by the Department of Defense. Two clinically relevant measures that are known to be altered following mTBI are the [18F] FDG-PET analysis of brain glucose dysregulation and miRNA serum biomarkers. Using a rodent model of projectile concussive impact (PCI) that produces an mTBI, we aim to determine whether these measures can be used prognostically to identify individuals with subacute or chronic deficits of mTBI, including behavioral deficits and chronic traumatic encephalopathy (CTE)-related neuropathology. Acute changes in these putative prognostic indicators following single and repeat PCI will be correlated with longitudinal behavioral deficits and chronic (3- and 6-month) molecular changes in CTE-related measures such as tau or amyloid. This study will provide information on highly clinically relevant paradigms that may have prognostic usefulness following mTBI and the subsequent recovery process, particularly for the subset of patients that have prolonged deficits. A primary focus of our research is finding effective treatment strategies for brain injury. This study will provide direction for future preclinical neuroprotection study design following single or repetitive mTBI, and guidance for potential clinical prognostic indicators.