Biomechanics of Pediatric Head Injury

创伤性脑损伤是儿童最常见的死亡原因，但其病因和治疗 儿科头部损伤仍然存在争议。此前，我们建立了一个跨学科的研究 采用急性动物实验、生物力学组织测试、回顾性临床研究、 拟人化的“玩偶”研究和计算机模拟。我们的数据显示，孩子们确实有 不同于成人的伤害机制，需要针对年龄的伤害预防策略和 治疗。在这次竞争性的更新中，我们建立在我们已经建立的基础上，既是为了深化我们的 了解基本的损伤机制，并增强我们的研究结果的临床相关性。我们会 用新的准备来补充我们现有的平台--生存研究，猪的行为结果， 脑血流量(CBF)测量、损伤后呼吸功能不全和损伤治疗研究 加强研究成果从实验室到临床环境的转化。 我们的总体假设是，未成熟的大脑快速旋转而不受冲击，通过 机械和生化信号，导致持续的功能和组织学异常。我们 将比较单发和多发头部损伤后的长期结果，以确定损伤间隔 调节损伤严重程度以及补充叶酸是否减轻轴突损伤(目标1)。我们将使用 人类计算模型将我们的动物研究扩展到周期性震动运动以估计贡献 谐波放大对伤害风险的影响(目标2)。利用动物实验和计算机模型，我们将 确定与CBF和脑干变形的局部快速下降相关的脑应变 与大脑自动调节功能丧失相关(目标3)。我们将通过改变 旋转方向和血管内皮细胞对高渗盐水的反应以验证急性机械和 生化信号通路。在头部损伤后出现呼吸功能不全的仔猪(目标4)中，我们 假设100%FiO2复苏可导致FREE介导的神经病理加重 彻底释放，我们将比较室内空气和100%FIO2，以及使用和不使用的结果 自由基清除剂，以验证功能。建议的研究针对我们的长远目标： 阐明儿童创伤性脑损伤的损伤机制和可能的治疗策略。

Traumatic brain injury is the most common cause of death in childhood, yet etiology and treatment of pediatric head injuries remain controversial. Previously, we established an interdisciplinary research paradigm using acute animal experiments, biomechanical tissue tests, retrospective clinical studies, anthropomorphic "doll" studies, and computational simulations. Our data show that children do indeed have injury mechanisms that are distinct from the adult, and require age-specific injury prevention strategies and treatments. In this competitive renewal, we build on the foundation we have established, both to deepen our understanding of basic injury mechanisms and to enhance the clinical relevance of our findings. We will supplement our current platforms with novel preparations - survival studies, porcine behavioral outcomes, cerebral blood flow (CBF) measures, post-injury respiratory insufficiency, and injury treatment studies - to enhance translation of research findings from the laboratory to the clinical setting. Our overall hypothesis is that rapid rotations of the immature brain without impact produce brain injury via both mechanical and biochemical signals, resulting in sustained functional and histological abnormalities. We will compare long-term outcomes after single and multiple head injuries to determine if injury interval modulates injury severity and if axonal injury is reduced with folate supplementation (Aim 1). We will use human computational models to extend our animal studies to cyclic shaking motions to estimate contribution of harmonic amplification to injury risk (Aim 2). Using animal experiments and computer models, we will identify cerebral strains associated with rapid regional decreases in CBF and brainstem deformations associated with loss of cerebral autoregulation (Aim 3). We will modulate regional deformations by altering rotation direction, and endothelial response with hypertonic saline to validate acute mechanical and biochemical signaling pathways. In piglets with respiratory insufficiency after head injury (Aim 4), we hypothesize that resuscitation with 100% FiO2 results in exacerbated neuropathology mediated by free radical release, and we will compare outcomes with room air and 100% FiO2, as well as with and without free radical scavengers to verify functionality. The proposed studies address our long-term goal of elucidating injury mechanisms and potential treatment strategies for traumatic brain injuries in children.