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.

每15秒，就有一个人遭受创伤性脑损伤（TBI）——导致超过530万美国人面临不同程度的脑损伤。与严重创伤性脑损伤相比，人们对轻度创伤性脑损伤或爆炸性脑损伤对神经元功能的影响知之甚少，从而导致认知缺陷和行为改变。此外，创伤性脑损伤后患者的预后也存在很大差异。受伤的严重程度可能部分取决于头部被击中的方式。事实上，头部损伤的机械性质与机动车事故、跌倒、运动、袭击和爆炸有很大不同。创伤性脑损伤的原因大多被描述为由于大脑在颅骨中的运动而引起的组织应变。对头部的不同生物力学损伤会导致整个大脑的不同载荷和变形模式。该项目的目标是确定与机动车事故（非撞击）相关的神经元细胞的机械载荷和变形与与钝器撞击（运动脑震荡）和爆炸暴露（极端率）相关的高速率和脉冲载荷在神经元细胞结构和功能方面的影响有何不同。有了适当的模型和信息来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社区将能够根据他们的研究需要复制损伤，以便更好地了解各种损伤的结果。这项研究将包括各级工程学生的参与，高级顶点设计项目，以及本科生和高中生的暑期课程。PI优先考虑并具有包容和照顾残疾学生的经验。与严重形式的创伤性脑损伤（TBI）相比，人们对轻度创伤性脑损伤或爆炸性脑损伤对细胞特性、神经网络和行为（认知缺陷的核心功能障碍）的影响知之甚少。轻度损伤不表现出明显的组织损伤，在严重的情况下，诊断经常被遗漏或不确定。创伤性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、跌倒、运动、袭击和爆炸中有很大的不同。该项目假设，局部力学的大小、速率和冲动都有助于引起不同的神经元结构和功能的改变，这些改变是TBI患者各种结果的基础。神经元和轴突病理已经很好地表征了动物模型从大的大脑变形，通常与头部旋转相关。因此，已知的TBI机制大多是根据组织应变来描述的。直到最近才有研究开始探索钝器撞击和爆炸伤害模式，但很少关注相关的高速率和脉冲负荷如何在神经元水平上造成损伤。该项目侧重于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预后的多样性很重要。定义性研究利用体外三维爆炸损伤神经元培养模型和已建立的体外拉伸损伤模型来复制三种损伤模式（非冲击、钝化和爆炸暴露）的应变、速率和脉冲。具体目标是：1)在3D体外blast模型中创建细胞活力暴露（相对于超压和脉冲）的剂量曲线；2)研究高应变率和脉冲加载对神经元结构改变的重要性；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.