The Effect of Sex Dimorphisms on TBI Injury and Recovery

项目摘要 仅在美国，每年估计有475，000名0-14岁的儿童遭受创伤性脑损伤 (TBI)超过7,000人死亡，60,000人住院，600,000人急诊。研究 这种普遍的情况使研究人员相信，神经发育中的两性异形可能 有助于观察到的TBI严重程度和恢复之间的差异，男性和女性儿童。然而，在这方面， 这些性二态性如何影响功能性神经网络重组仍然是未知的， TBI后认知、行为和运动功能表现的后续变化。在本提案中，我们 试图通过研究二态神经解剖学对功能的影响来解决这一知识缺口， 在我们的转化小儿猪TBI模型中的神经网络恢复。我们假设先天性两性异形 将与TBI后神经网络损伤和重组的特定差异相关 在急性、亚急性和慢性时间点的认知、行为和运动功能表现。的 这项工作的贡献是非常重要的，因为成功完成这项建议将改善目前的 了解两性异形如何可能作为一个发病前的风险因素，使男性和女性 儿童TBI的严重程度和恢复程度不同。这项研究也具有广泛的影响， 了解其他神经损伤和疾病的性别差异。最后，在平移猪模型中进行测试 由于猪和人之间的代表性脑解剖学和TBI病理生理学， 提高研究成果的转化潜力。

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.