The Systemic Nature of Severe Traumatic Brain Injury

Severe traumatic brain injury (sTBI) is a devastating condition with no targeted therapies available to prevent secondary injury. Previous studies have demonstrated that brain injury in adolescents initiates an acute and robust immune response characterized by disruption of the blood-brain barrier and the formation of autoantibodies. Alterations in the gut-brain axis may contribute to increased immune activation and autoantibody formation following sTBI. The primary objective of this study is to better understand the immune mechanisms involved in the interaction between brain injury and changes in gut permeability through the gut-brain axis. To investigate these mechanisms, the study will use a multi-platform metabolomics approach in combination with ribonucleic acid (RNA) sequencing, cell-free deoxyribonucleic acid (cfDNA) analysis, and blood chemistry. These analyses will be used to evaluate early immune activation and the mechanisms associated with secondary and tertiary brain injury and neurodegeneration in adults with sTBI.

Inclusion Criteria: * All patients must be between the ages of 18 to 65 at time of enrollment * Study group cohort will consist of at least 20 patients admitted with severe TBI, defined as a GSC less than or equal to 8 with evidence of intracranial pathology on imaging. * Trauma control cohort will include at least 10 patients matched on demographics and injury patterns without traumatic brain injury. * Healthy control cohort will be comprised of 10 patients without acute traumatic injury or illness, matched to the sTBI patients based on demographics and medical comorbidities. Exclusion Criteria: * Pregnant Patients * Prisoners * Patients less than 18 years of age or greater than 65 years of age * Patients with a penetrating brain injury mechanism, known neurodegenerative or psychiatric disorders, prior known traumatic brain injury, intracranial neoplasm, patients receiving massing transfusion or blood products prior to arrival, terminal illness or not expected to survive, confirmed or suspected brain death, known autoimmune or immunological condition, receiving immunosuppressant or immunomodulatory therapies, having a cardiac event leading to the injury, or for whom consent is unable to be obtained.