Stereotaxic Accessory for Reproducible Neurotrauma

描述（由申请人提供）：本申请是为了继续开发一种商业、电磁、立体定向配件，用于对小鼠或大鼠头部或暴露的皮质的可选位置产生精确和可测量的影响。该装置将用于研究创伤性脑损伤。我们的设计目标是：(1)精确控制冲击的位置和方向；(2)控制冲击的速度和位移；(3)测量这些参数，以及力和能量，以确认和表征创伤。与健康相关：对创伤力学的更好理解将增加我们对损伤的理解，允许数值模型的验证，并改善脑损伤的管理和头部保护的设计。创伤性脑损伤（TBI）引起的冲击完整的头骨是最常见的形式的头部损伤。关于严重、震荡和次震荡事件的长期影响仍有未解决的问题。撞击时神经元应变的程度及其与随后损伤的关系尚不清楚。啮齿动物脑损伤模型是常见的，但损伤装置功能有限，效果多变，影响参数仍不明确。这些缺陷限制了研究人员重复他人工作和确定神经元损伤病因的能力。第一阶段的结果：目的1：构建立体定向附件的原型，以传递大鼠或小鼠的冲击神经损伤。该装置与大多数市售立体定向仪器兼容。一个紧凑的电磁执行器被用来提供一个指定的压痕深度和速度到头骨或大脑。立体定向装置的线性和角度定位能力控制着撞击的位置和方向。头部保持组件进行了修改，以支持头部牢固，同时分配反作用力。目的2：确认该装置在啮齿动物模型中使用新位置和冲击方向产生重复损伤的能力。研究了撞击位置和方向对幼龄大鼠神经元退行性变的影响。新装置产生的冲击在位移和能量方面与重量下降损伤相当，但具有侧向位置和方向。测定并比较创伤后24小时细胞死亡模式。第二阶段的具体目标：目标1 -技术：将力、速度、加速度和触摸传感器整合到基本设备中。将对撞击器进行仪器检测，以实时描述每个事件的特征。目的2-验证：使用该装置对成年C57BU6小鼠在电磁控制皮质损伤（ECI）后的组织学和行为变化进行严格和完整的验证。“控制性皮质冲击”（CCI）模型已广泛应用于小鼠；各种气动装置都会造成伤害。在我们的ECI设备被广泛接受之前，我们必须证明它可以用来复制先前研究中看到的行为变化。

DESCRIPTION (provided by applicant): This application is to continue development of a commercial, electromagnetic, stereotaxic accessory for inducing precise and measurable impacts to selectable locations on the head or exposed cortex of a mouse or rat. The device will be used in the study of traumatic brain injury. Our design objectives are to: (1) control precisely the location and direction of impact; (2) control the velocity and displacement of the impact; and (3) measure these parameters, as well as force and energy, to confirm and characterize the trauma. Health-relatedness: Improved understanding of trauma mechanics will increase our understanding of injury, allow validation of numerical models, and improve management of brain injury and the design of head protection. Traumatic brain injury (TBI) caused by impact to the intact skull is the most prevalent form of head injury. There are unresolved questions about long-term effects of severe, concussive and sub-concussive events. The degree of neuronal strain at impact, and its relationship to subsequent impairment are not well understood. Rodent models of brain injury are common, but injury devices are limited in function, widely variable in effect, and the parameters of impact remain poorly defined. These deficiencies limit the ability of researchers to duplicate the work of others and to define the etiology of neuronal injury. Results from Phase I: AIM 1: Construct a prototype stereotaxic accessory to deliver impact neurotrauma to rat or mouse. The device is compatible with most commercially available stereotaxic instruments. A compact electromagnetic actuator is used to provide a specified indentation depth and speed to the skull or brain. The linear and angular positioning capabilities of the stereotaxic device control the location and direction of impact. Head-holding components were modified to support the head firmly while distributing reaction forces. AIM 2: Confirm the ability of the device to produce a repeatable injury in a rodent model using novel location and direction of impact. A focused study was performed to investigate the effect of impact location and direction on neuronal degeneration in the infant rat. The new device was used to generate an impact equivalent in terms of displacement and energy to weight drop injury, but with a lateral location and direction. Patterns of cell death 24 hours post-trauma were determined and compared. Specific Aims for Phase II: Aim 1 - Technological: Incorporate force, velocity, acceleration, and touch sensors into the basic device. The impacter will be instrumented to characterize each event in real time. Aim 2- Validation: Perform rigorous and complete validation of histological and behavioral changes in the adult C57BU6 mouse after electromagnetically controlled cortical injury (ECI) with this device. The "controlled cortical impact" (CCI) model has been widely used in mice; injuries have been produced with a variety of pneumatic devices. Before our ECI device can be widely accepted we must show that it can be used to duplicate behavioral changes seen in prior studies.