The Effect of Sex Dimorphisms on TBI Injury and Recovery

性别二态性对 TBI 损伤和恢复的影响

• 批准号: 10643320
• 负责人: Franklin D West
• 金额: $ 17.75万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10643320
• 关键词: 3-Dimensional; Acute; Address; Affect; Age; American; Anatomy; Atrophic; Behavior; Behavioral; Body Size; Brain; Cause of Death; Cell physiology; Cessation of life; Child; Childhood; Chronic; Cognition; Cognitive; Cognitive deficits; Compensation; Data; Development; Disease; Dorsal; Emergency department visit; Emotional; Endocrine; Family suidae; Female; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Hippocampus; Hospitalization; Human; Hypothalamic structure; Impairment; Injury; Knowledge; Learning; Magnetic Resonance Imaging; Measures; Memory; Modeling; Motor; Neuroanatomy; Outcome; Pathway interactions; Patients; Performance; Pituitary Gland; Positioning Attribute; Predisposing Factor; Recovery; Recovery of Function; Reporting; Research Personnel; Resolution; Rest; Risk Factors; Rodent Model; Severities; Sex Differences; Structure; Testing; Time; Traumatic Brain Injury; Traumatic Brain Injury recovery; United States; Work; aged; brain volume; deep learning model; disability; gait examination; graph theory; gray matter; improved; innovation; insight; male; motor function recovery; nerve injury; neural; neural network; neurodevelopment; neuroprotection; novel; object recognition; pediatric traumatic brain injury; porcine model; prognostic model; psychosocial; putamen; response to injury; restoration; sex; sexual dimorphism; social; translational potential; white matter

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.

项目概要 仅在美国，每年就有估计有 475,000 名 0-14 岁儿童遭受创伤性脑损伤 (TBI) 造成超过 7,000 人死亡、60,000 人住院治疗以及 600,000 人次急诊就诊。研究 这种普遍的情况使研究人员相信神经发育中的性别二态性可能 有助于观察到男女儿童 TBI 严重程度和恢复情况的差异。然而， 目前尚不清楚这些性别二态性如何影响功能性神经网络重组和 TBI 后认知、行为和运动功能表现的后续变化。在这个提案中，我们 通过研究二态神经解剖学对功能的影响来寻求解决这一知识差距 我们的转化儿科猪 TBI 模型中的神经网络恢复。我们假设先天性别二态性 仔猪中的差异也与 TBI 后神经网络损伤和重组的特定差异相关 作为急性、亚急性和慢性时间点的认知、行为和运动功能表现。这 这项工作的贡献非常重要，因为成功完成这项提案将改善当前的情况 了解性别二态性如何作为导致男性和女性易感的病前危险因素 儿童遭受不同程度的 TBI 严重程度和恢复情况。这项研究还具有广泛的影响 了解其他神经损伤和疾病的性别差异。最后，在转化猪模型中进行测试 由于猪和人类之间具有代表性的大脑解剖学和 TBI 病理生理学，因此具有创新性，因此 提高研究结果的转化潜力。