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Abstract
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. The pediatric population is at a particularly high risk for TBI due to a greater propensity for falls and unintentional injury. Furthermore, due to ongoing neural maturation, children that sustain a TBI are at increased risk of developing long term neurological deficits including motor, cognitive, and behavioral impairments. Early detection of injury location and severity allows for determination of prognosis and the development of rehabilitation plans; however, conventional magnetic resonance imaging (MRI) sequences often lack sensitivity to detect microstructural injury to white matter. Diffusion Tensor Imaging (DTI) tractography is a highly sensitive MRI technique that produces 3-dimensional reconstruction of specific white matter tracts to measure the movement of water molecules, thus allowing for analysis of white matter integrity throughout the brain. Furthermore, no approved TBI therapeutic is available to blunt harmful secondary injury cascades. However, recent preclinical research has provided early evidence that the bidirectional communication between the gut microbiome and brain, termed the microbiome-gut- brain-axis (MGBA), presents a viable therapeutic opportunity to reduce neural injury severity by repopulating the gut with healthy bacterial communities via fecal microbial transplant (FMT). While a myriad of TBI therapeutics have shown promise in preclinical rodent studies, all have failed to demonstrate clinical success, likely due to innate differences in anatomy and physiology between humans and rodents. The piglet model has proven to reliably recapitulate the pathophysiology and functional deficits of human pediatric TBI. Therefore, further research employing a highly translational piglet TBI model is needed to elucidate sensitive prognostic neuroimaging biomarkers and to develop novel therapeutics that will each contribute to improved long-term outcomes for patients. The objectives of these studies were to 1) use DTI tractography to develop novel neuroimaging prognostic biomarkers by determining the correlation between acute white matter integrity and subacute gait deficits and 2) test the efficacy of therapeutic FMT utilizing a pediatric piglet TBI model.