Stereotaxic Accessory for Reproducible Neurotrauma

描述(由申请人提供)：该申请是为了继续开发一种商业、电磁、立体定位附件，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。该设备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。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，允许验证数字模型，并改进脑损伤的管理和头部保护的设计。颅脑损伤是颅脑损伤中最常见的一种形式，是颅脑损伤最常见的形式。关于严重、脑震荡和亚脑震荡事件的长期影响，还有一些悬而未决的问题。撞击时神经元应变的程度及其与后续损伤的关系尚不清楚。脑损伤的啮齿动物模型很常见，但损伤装置的功能有限，效果差异很大，撞击参数仍不明确。这些缺陷限制了研究人员重复其他人的工作并定义神经元损伤的病因的能力。第一阶段的结果：目标1：构建一个原型立体定位附件来传递冲击性神经损伤给大鼠或小鼠。该装置与大多数商业上可用的立体定向仪器兼容。紧凑型电磁致动器用于为头骨或大脑提供特定的压痕深度和速度。立体定位仪的线性和角度定位能力控制着撞击的位置和方向。对头部保持部件进行了改进，以在分配反作用力的同时牢固地支撑头部。目的2：利用新的撞击位置和方向，确认该装置在啮齿动物模型中产生可重复损伤的能力。为探讨撞击部位和方向对幼年大鼠神经元变性的影响，进行了一项重点研究。这种新的装置被用来产生与重量跌落损伤的位移和能量相等的冲击力，但具有横向位置和方向。测定并比较创伤后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整合到基本设备中。冲击器将被测量，以实时描述每个事件的特征。目的2-验证：使用该设备对成年C57BU6小鼠电磁控制皮质损伤(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)模型在小鼠身上得到了广泛的应用；各种气动装置也造成了损伤。在我们的ECI设备被广泛接受之前，我们必须证明它可以用于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.