The purpose of this collaborative project is to identify robust biomarkers that predict chronic neuronal dysfunction following traumatic brain injury {TBI). Evaluating TBl-induced pathology and dysfunction in the brain can be challenging. We hypothesize that the retina can serve as a surrogate to monitor the rate of neurodegeneration occurring in the brain following injury. Furthennore, we hypothesize that bloodbased biomarkers correlate with TBl-mediated neurodegeneration in the retina and brain. Our collaborative project will leverage the unique strengths of each investigative team by sharing samples among sites to coordinate and harmonize the outcomes used in this study. While every project will not use identical outcomes, our shared outcomes will be uniform among studies. All three animal model sites can leverage their unique strengths. The Gainesville VA has access to a state of the art 11 tesla MRI magnet and will receive fixed brain samples from each site for ex vivo imaging. The Iowa City VA will quantify axons in the optic nerve and conduct immunohistochemical analysis of retinal and brain sections from all sites. The serum samples from cohorts all cohorts will be analyzed by the Iowa City and Gainesville VA to examine the expression of autoantibodies (Iowa), brain and retinal protein expression in the blood (Gainesville), and cytokine expression in the blood (Gainesville). The clinical studies of Veterans with TB/ will also be coordinated among sites. The Atlanta VA will assess retinal function and structure of Veterans with TB/. The Gainesville VA will coordinate and synchronize the cognitive analysis of subjects between the Atlanta and Gainesville VAs. The Gainesville VA will also perform, analyze, and interpret MRls on Veterans with TB/. Each project will perform an independent statistical analysis on the data. In addition, the San Francisco VA will coordinate the curation of all data generated in each project and upload the data to an open data commons. The San Francisco VA will conduct big data and pattern recognition analysis using the entire set of data from all projects. The San Francisco VA will also use the biomechanical modeling data generated from Project 4 to determine how induction of injury and transmission of energy affects long-term neurological outcomes. Project Summary/Abstract