Linking how the mechanics of high rate and impulse of loading to the brain leads to varying types and levels of damage to neuronal structure and function.

将高速率和脉冲负荷的机制如何导致对神经元结构和功能的不同类型和水平的损伤联系起来。

• 批准号: 1706157
• 负责人: Bryan Pfister
• 金额: $ 30.98万
• 依托单位: New Jersey Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1706157&HistoricalAwards=false
• 关键词: Linking; how; mechanics; rate; impulse

PI: Pfister, Bryan Proposal: 1706157 Every fifteen seconds, someone suffers a traumatic brain injury (TBI) -- leading to over 5.3 million Americans coping with varying severity of brain injuries. Compared to severe TBI, little is known about the consequences of mild TBI or blast TBI on neuronal function that can then lead to cognitive deficits and changes in behavior. In addition, there is wide variability in patient outcomes after a TBI. Injury severity may in part depend on how the head is hit. Indeed, the mechanical nature of injury to the head varies greatly from motor vehicle accidents, falls, sports, assaults, and exposure to blasts. The cause of TBI has mostly been described in terms of tissue strains due to the brain motion in the skull. Distinctively different biomechanical insults to the head will translate to unique loading and deformation patterns throughout the brain. The project goal is to define how the mechanical loading and deformation of neuronal cells associated with motor vehicle accidents (non-impact) differ from high rate and impulse loading associated with blunt impact (sport concussion) and blast exposure (extreme rate) in terms of the effect on structure and function of neuronal cells. With appropriate models and information establishing how biomechanics plays an important role in neuronal structure and function, the TBI community will be able to replicate injury as needed for their studies in order to better understand various injury outcomes. This research will include the participation of engineering students at all levels, senior capstone design projects, and a summer programs for undergraduate and high school students. The PI prioritizes and has experience with including and accommodating students with disabilities.Compared to severe forms of traumatic brain injury (TBI), little is known about the consequences of mild TBI or blast TBI on cellular properties, neural networks, and behavior -- the dysfunction at the core of cognitive deficits. Mild injuries do not show the overt tissue damage present in severe cases, and diagnoses are often missed or uncertain. The variations in TBI are also an important biomechanical problem. The mechanical nature of injury to the head can vary greatly between motor vehicle accidents, falls, sports, assaults, and exposure to blasts. The project hypothesizes that the magnitude, rate and impulse of the local mechanics each contribute to cause different alterations in neuronal structure and function that underlie the variety of outcomes seen in TBI patients. Neuronal and axon pathology have been well characterized in animal models from large brain deformations that are typically associated with head rotations. Accordingly, the known mechanisms of TBI have mostly been described in terms of tissue strains. Only recently has research begun exploring blunt impact and blast modes of injury, but with little focus on how the associated high rate and impulse loading causes damage at the neuronal level. This project focuses on defining how these vastly different biomechanical loading parameters affect structure and function of the neuron, which may shed light on different mechanisms of injury that may be important to the diversity of patient outcomes in head injury. Defining studies make use of an in vitro, 3D neuronal culture model of blast injury and an established in vitro stretch injury model to replicate strains, rates and impulses of three modes (non-impact, blunt pact and blast exposure) of injury. The specific aims are to: 1) create a dose curve of cell viability to blast exposure (vs. overpressure and impulse) in a 3D in vitro blast model; 2) investigate the importance of high strain rate and impulse loading to alterations in neuronal structure; and 3) investigate the importance of high strain rate and impulse loading on neuronal electrical activity.

PI：Pfister，Bryan提案：1706157每十五秒钟，有人遭受创伤性脑损伤（TBI） - 导致超过530万美国人应对脑损伤严重程度的不同。与严重的TBI相比，对轻度TBI或BLAST TBI对神经元功能的后果知之甚少，这可以导致认知缺陷和行为变化。此外，TBI后患者的预后有很大的差异。受伤严重程度可能部分取决于头部的击中。实际上，头部受伤的机械性质与机动车事故，跌倒，运动，攻击和暴露于爆炸的情况大不相同。由于头骨的脑运动，TBI的原因主要是用组织菌株描述的。对头部的截然不同的生物力学侮辱将转化为整个大脑中独特的负载和变形模式。项目目标是定义与机动车事故相关的神经元细胞的机械负荷和变形与与钝性撞击（运动脑震荡）和爆炸暴露（极端速率）相关的高速率和冲动载荷相关的神经元细胞的变形（非影响力）如何在神经元细胞的结构和功能方面有所不同。 通过适当的模型和信息，确定生物力学如何在神经元结构和功能中起重要作用，TBI社区将能够根据需要进行研究以更好地了解各种损伤结果。 这项研究将包括各个级别的工程专业学生的参与，高级顶峰设计项目以及针对本科和高中生的夏季计划。 PI优先考虑并具有包括和容纳残疾学生的经验。轻度伤害并未显示在严重情况下存在明显的组织损伤，并且诊断常常被遗漏或不确定。 TBI的变化也是一个重要的生物力学问题。头部受伤的机械性质在机动车事故，跌落，运动，攻击和暴露于爆炸之间的机械性质可能会有所不同。 该项目假设局部力学的幅度，速率和冲动都导致神经元结构和功能的不同变化，这些变化是TBI患者中各种结果的基础。神经元和轴突病理学在来自大脑变形的动物模型中已得到很好的特征，这些大脑变形通常与头部旋转相关。因此，已知的TBI机制主要是用组织菌株描述的。直到最近，研究才开始探索钝性影响和爆炸损伤模式，但很少关注相关的高率和脉冲负荷如何在神经元水平上造成损害。 该项目着重于定义这些截然不同的生物力学负载参数如何影响神经元的结构和功能，这可能会阐明不同的损伤机制，这可能对头部损伤中患者的多样性很重要。 定义研究利用了爆炸损伤的体外，3D神经元培养模型，以及已建立的体外拉伸损伤模型，以复制三种模式（非影响力，钝协议和爆炸暴露）的菌株，速率和冲动。具体目的是：1）在3D体外爆炸模型中创建细胞活力的剂量曲线以爆炸暴露（与超压和冲动）； 2）研究高应变速率和脉冲负荷对神经元结构改变的重要性； 3）研究高应变速率和脉冲负载对神经元电活动的重要性。