Stereotaxic Accessory for Reproducible Neurotrauma

描述（由申请人提供）：本申请旨在继续开发一种商用电磁立体定位附件，用于对小鼠或大鼠头部或暴露皮质上的可选位置产生精确且可测量的冲击。该器械将用于创伤性脑损伤的研究。我们的设计目标是：（1）精确控制撞击的位置和方向;（2）控制撞击的速度和位移;（3）测量这些参数以及力和能量，以确认和描述创伤。健康相关性：提高对创伤力学的理解将增加我们对损伤的理解，允许验证数值模型，并改善脑损伤的管理和头部保护的设计。创伤性脑损伤（TBI）是由撞击完整颅骨引起的最常见的头部损伤形式。关于严重的、震荡性和亚震荡性事件的长期影响，还有一些尚未解决的问题。神经元应变的程度，在影响，其关系，随后的损害还没有得到很好的理解。啮齿动物脑损伤模型是常见的，但损伤装置的功能有限，效果差异很大，并且撞击参数仍然定义不清。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：构建一个原型立体定位配件，以提供冲击神经创伤大鼠或小鼠。该器械与大多数市售立体定位仪器兼容。紧凑的电磁致动器用于向颅骨或大脑提供指定的压痕深度和速度。立体定位装置的线性和角度定位能力控制撞击的位置和方向。修改了头部固定组件，以在分配反作用力的同时牢固地支撑头部。目的2：使用新的撞击位置和方向，确认器械在啮齿动物模型中产生可重复损伤的能力。本研究旨在探讨撞击位置和方向对幼年大鼠神经元变性的影响。新器械用于产生与重物跌落损伤等同的位移和能量冲击，但具有横向位置和方向。确定并比较创伤后24小时的细胞死亡模式。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纳入基本设备。将对撞击器进行仪表化处理，以真实的时间表征每个事件。目标2-验证：使用该器械对成年C57 BU 6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。“受控皮质撞击”（CCI）模型已被广泛用于小鼠;各种气动装置已造成损伤。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 //: 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.