The Effect of Sex Dimorphisms on TBI Injury and Recovery

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Project Summary Every year in the United States alone, an estimated 475,000 children aged 0-14 suffer a traumatic brain injury (TBI) with more than 7,000 deaths, 60,000 hospitalizations, and 600,000 emergency department visits. Study of this prevalent condition has led researchers to believe that sexual dimorphisms in neurodevelopment may contribute to the observed differences in TBI severity and recovery between male and female children. However, it remains unknown how these sexual dimorphisms influence functional neural network reorganization and subsequent changes in cognitive, behavioral, and motor function performance post-TBI. In this proposal, we seek to address this knowledge gap by investigating the influence of dimorphic neuroanatomy on functional neural network recovery in our translational pediatric pig TBI model. We hypothesize innate sexual dimorphisms in piglets will correlate with specific differences in post-TBI neural network damage and reorganization as well as cognitive, behavioral, and motor function performance at acute, sub-acute, and chronic time points. The contribution of this work is highly significant as successful completion of this proposal will improve the current understanding of how sexual dimorphisms may act as a premorbid risk factor that predisposes male and female children to differing levels of TBI severity and recovery. This study also has broad reaching implications in understanding sex differences in other neural injuries and diseases. Finally, testing in a translational pig model is innovative due to representative brain anatomy and TBI pathophysiology between pigs and humans, thus improving the translational potential of study findings.