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.

PI：Pfister，Bryan提议：每15秒就有1706157人遭受创伤性脑损伤--导致530多万美国人正在应对不同严重程度的脑损伤。与重型脑损伤相比，轻度脑损伤或冲击性脑损伤对神经功能的影响知之甚少，这些脑损伤会导致认知障碍和行为改变。此外，颅脑损伤后患者的预后也有很大的差异。受伤的严重程度可能在一定程度上取决于头部被击中的方式。事实上，头部损伤的机械性质从机动车事故、跌倒、运动、袭击和暴露在爆炸中都有很大的不同。颅脑损伤的原因主要是颅脑运动引起的组织劳损。不同的生物力学对头部的侮辱将转化为整个大脑独特的负荷和变形模式。该项目的目标是确定与机动车辆事故(非撞击)相关的神经细胞的机械载荷和变形在对神经细胞结构和功能的影响方面与与钝器撞击(运动脑震荡)和冲击波暴露(极端速率)相关的高速率和脉冲载荷有何不同。有了适当的模型和信息，确定了生物力学如何在神经元结构和功能中发挥重要作用，脑损伤社区将能够根据他们的研究需要复制损伤，以便更好地了解各种损伤结果。这项研究将包括所有级别的工程学学生的参与，高级顶峰设计项目，以及本科生和高中生的暑期计划。与严重形式的创伤性脑损伤(TBI)相比，人们对轻度脑损伤或冲击性脑损伤对细胞特性、神经网络和行为的影响--认知缺陷的核心功能障碍--知之甚少。轻度损伤不会像严重病例那样显示出明显的组织损伤，而且诊断经常被遗漏或不确定。颅脑损伤的变异也是一个重要的生物力学问题。头部损伤的机械性质在机动车事故、摔倒、运动、袭击和暴露在爆炸中可能有很大的不同。该项目假设，局部机制的大小、速率和脉冲每个都会导致神经元结构和功能的不同变化，这些变化是脑外伤患者看到的各种结果的基础。神经元和轴突病理在大型脑变形的动物模型中得到了很好的表征，这种变形通常与头部旋转有关。因此，已知的脑损伤机制主要是从组织应变的角度来描述的。直到最近，研究才开始探索钝性撞击和冲击波损伤的模式，但很少关注相关的高速率和脉冲加载如何在神经元水平上造成损伤。本项目的重点是确定这些差异很大的生物力学载荷参数如何影响神经元的结构和功能，这可能有助于揭示不同的损伤机制，这可能对颅脑损伤患者预后的多样性具有重要意义。定义性研究利用冲击伤的体外三维神经元培养模型和已建立的体外牵张损伤模型来复制三种损伤模式(非撞击、钝性接触和冲击波暴露)的应变、速率和脉冲。其具体目的是：1)在三维体外BLAST模型中建立爆炸暴露(与超压和脉冲)的细胞活性的剂量曲线；2)研究高应变率和脉冲载荷对神经元结构改变的重要性；以及3)研究高应变率和脉冲载荷对神经元电活动的重要性。

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.