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Biomechanics of Pediatric Head Injury

小儿头部损伤的生物力学

基本信息

批准号：
8063084
负责人：
Susan Sheps Margulies
金额：
$ 45.72万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-05-15 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8063084
关键词：
Acute Address Adult Age Air Anatomy Animal Experiments Animal Model Animals Attenuated Back Behavior Behavioral Biochemical Biomechanics Brain Brain Injuries Brain Stem Cause of Death Cell Death Cerebral perfusion pressure Cerebrovascular Circulation Cerebrum Child Childhood Childhood Injury Clinical Clinical Research Cognitive Computer Simulation Contusions Craniocerebral Trauma Data Diffuse Edema Etiology Event Family suidae Folate Folic Acid Foundations Free Radical Scavengers Free Radicals Frequencies Funding Goals Head Homeostasis Human Hypoxia Infant Injury Interdisciplinary Study Intervention Intracranial Hemorrhages Intracranial Pressure Ischemic Brain Injury Laboratory Finding Measures Mechanics Mediating Microscopic Microspheres Modeling Motion Motor Multiple Head Injuries Nerve Degeneration Newborn Infant Optics Outcome Pattern Preparation Prevention Prevention strategy Recovery Recovery of Function Research Research Personnel Respiratory Insufficiency Resuscitation Risk Rotation Saline Severities Signal Pathway Signal Transduction Simulate Spatial Distribution Spectrum Analysis Supplementation Swelling Testing Time Tissues Toddler Translational Research Traumatic Brain Injury Unconscious State animal tissue base brain tissue clinically relevant experience functional outcomes human tissue improved injured injury prevention instrument neuropathology nitrone novel pressure programs repaired research study response treatment strategy white matter

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：创伤性脑损伤是儿童期最常见的死亡原因，但儿童头部损伤的病因和治疗仍然存在争议。此前，我们利用急性动物实验、生物力学组织测试、回顾性临床研究、拟人化“娃娃”研究和计算模拟建立了跨学科研究范式。我们的数据表明，儿童确实具有与成人不同的损伤机制，并且需要针对特定年龄的损伤预防策略和治疗。在这次竞争性更新中，我们在已经建立的基础上继续发展，既加深了我们对基本损伤机制的理解，又增强了我们研究结果的临床相关性。我们将用新的准备工作来补充我们现有的平台——生存研究、猪行为结果、脑血流量（CBF）测量、损伤后呼吸功能不全和损伤治疗研究——以加强研究成果从实验室到临床的转化。我们的总体假设是，未成熟大脑在没有冲击的情况下快速旋转会通过机械和生化信号产生脑损伤，导致持续的功能和组织学异常。我们将比较单次和多次头部损伤后的长期结果，以确定损伤间隔是否会调节损伤的严重程度，以及补充叶酸是否可以减少轴突损伤（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循环振动运动，以估计谐波放大对伤害风险的贡献（目标 2）。通过动物实验和计算机模型，我们将确定与 CBF 快速局部减少相关的脑应变以及与大脑自动调节丧失相关的脑干变形（目标 3）。我们将通过改变旋转方向和高渗盐水的内皮反应来调节区域变形，以验证急性机械和生化信号通路。对于头部受伤后呼吸功能不全的仔猪（目标 4），我们假设使用 100% FiO2 进行复苏会导致自由基释放介导的神经病理学加剧，并且我们将比较室内空气和 100% FiO2 以及使用和不使用自由基清除剂的结果，以验证功能。拟议的研究解决了我们阐明儿童创伤性脑损伤的损伤机制和潜在治疗策略的长期目标。