Project Description Narrative:
Traumatic brain injury (TBI) can have devastating effects that endure for years after injury. This project team's human study, recently published in JAMA Surgery, is the first to show that after complicated TBI, patients who underwent surgery unrelated to their brain injury had worse functional and cognitive outcomes at two weeks and six months. These observational data demonstrate an association, but cannot imply a causal relationship. This project will implement a preclinical model, which can control the confounding variables that cannot be manipulated in a clinical setting and establish a causal relationship between peripheral injuries/surgeries and worse outcomes after TBI. Therefore, this project will positively impact health in Wisconsin by understanding injury mechanisms that can worsen outcomes.
The outcomes of this study have important clinical implications regardless of the results. A causal link between surgery shortly after TBI and neurological outcomes, as hypothesized, would change clinical management. Alternatively, the lack of a direct link would improve the confidence that surgery for non-TBI related injuries does not cause harm. This study will be the first to definitively test this important question.
The research team's overarching hypothesis is that inflammatory mediators worsen brain injury. The inflammatory responses to surgery and trauma are remarkably similar, even though surgery is a controlled event under anesthesia, whereas trauma is an unexpected event in an unanesthetized state. The outcomes assessed, including behaviors and blood-based biomarkers, will be correlated with detailed histological evaluations that cannot be performed in humans. The behavioral outcomes are rigorous assessments that quantify TBI-related deficits in functions and cognition. The blood-based biomarkers of brain and peripheral injury have high translational value since they are FDA-approved for human TBI and examined in many human TBI studies.
The study is led by a clinician-scientist that authored the human TBI study. The team extends ongoing collaborations between him and a surgeon investigator, biomechanical engineer, behavioral expert, and imaging specialist, who are uniquely suited to complete the multi-disciplinary aims with high scientific and clinical value.
Long-term, this project will improve health equity because TBI disproportionately afflicts under-represented and vulnerable populations. This study is vital to understand the pathophysiological mechanisms and causal effects between peripheral injuries and TBI. As such, this is a pressing healthcare issue, which is highly relevant to the people of Wisconsin.