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.

主要研究者：Pfister，Bryan提案：1706157每15秒，就有一个人遭受创伤性脑损伤（TBI）-导致超过530万美国人应对不同程度的脑损伤。与严重TBI相比，人们对轻度TBI或爆炸性TBI对神经元功能的影响知之甚少，这些影响可能导致认知缺陷和行为改变。此外，TBI后患者结局存在广泛的差异。受伤的严重程度可能部分取决于头部是如何被击中的。事实上，头部损伤的机械性质与机动车事故、福尔斯、运动、袭击和爆炸有很大不同。TBI的原因大多被描述为由于颅骨中的脑运动引起的组织应变。对头部的明显不同的生物力学损伤将转化为整个大脑的独特载荷和变形模式。该项目的目标是确定与机动车事故（非冲击）相关的神经元细胞的机械载荷和变形如何不同于与钝力冲击（运动脑震荡）和爆炸暴露（极端速率）相关的高速率和脉冲载荷对神经元细胞结构和功能的影响。 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发挥重要作用，TBI社区将能够根据研究需要复制损伤，以便更好地了解各种损伤结果。 这项研究将包括各级工程专业学生的参与，高级顶点设计项目，以及本科生和高中生的暑期课程。PI优先考虑并拥有包容和容纳残疾学生的经验。与严重形式的创伤性脑损伤（TBI）相比，人们对轻度TBI或爆炸性TBI对细胞特性，神经网络和行为的后果知之甚少-认知缺陷的核心功能障碍。轻度损伤并不表现出严重病例中明显的组织损伤，诊断往往被遗漏或不确定。 TBI的变异性也是一个重要的生物力学问题。在机动车事故、福尔斯、运动、袭击和爆炸中，头部损伤的机械性质可能差异很大。 该项目假设局部力学的幅度、速率和脉冲各自导致神经元结构和功能的不同改变，这些改变是TBI患者中观察到的各种结果的基础。神经元和轴突病理学已经在动物模型中得到很好的表征，这些动物模型来自通常与头部旋转相关的大的脑变形。因此，TBI的已知机制大多是根据组织应变来描述的。直到最近，研究才开始探索钝性冲击和爆炸的损伤模式，但很少关注相关的高速率和脉冲载荷如何在神经元水平上引起损伤。 该项目的重点是定义这些截然不同的生物力学载荷参数如何影响神经元的结构和功能，这可能会揭示不同的损伤机制，这可能对头部损伤患者结局的多样性很重要。 定义性研究利用冲击伤的体外3D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（非冲击、钝击和冲击暴露）的应变、速率和脉冲。具体目标是：1）在3D体外爆炸模型中创建细胞活力对爆炸暴露（相对于超压和脉冲）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.