The Effect of Sex Dimorphisms on TBI Injury and Recovery

项目摘要 仅在美国，估计每年就有47.5万名0-14岁的儿童遭受创伤性脑损伤 (TBI)有7000多人死亡，6万人住院，60万人去急诊科就诊。的研究 这种流行的疾病使研究人员相信，神经发育中的性二型可能 导致观察到的男性和女性儿童在脑损伤严重程度和恢复方面的差异。然而， 目前尚不清楚这些性二态如何影响功能神经网络重组和 脑外伤后认知、行为和运动功能表现的后续变化。在这项提案中，我们 通过研究双形态神经解剖学对功能的影响，试图解决这一知识鸿沟 神经网络在我们的平移型小儿颅脑损伤模型中的恢复。我们假设先天的性别二型性 将与脑创伤后神经网络损伤和重组的特定差异相关 作为在急性、亚急性和慢性时间点的认知、行为和运动功能表现。这个 这项工作的贡献是非常重要的，因为这项提案的成功完成将改善目前的 了解性二型性如何可能作为发病前的危险因素，使男性和女性倾向于 儿童对不同程度的脑损伤的严重性和恢复情况。这项研究也具有广泛的深远意义 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 由于具有代表性的脑解剖和人与猪之间的脑损伤病理生理学，具有创新性，因此 提高研究成果的翻译潜力。

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.