Stereotaxic Accessory for Reproducible Neurotrauma

用于可重复性神经创伤的立体定位附件

• 批准号: 7050764
• 负责人: CHARLES William SCOUTEN
• 金额: $ 39.17万
• 依托单位: MYNEUROLAB.COM
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7050764
• 关键词: brain; brain injury; head; injury; measurement; model; skull; trauma

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.

描述（由申请人提供）：本申请旨在继续开发一种商业电磁立体定位配件，用于对小鼠或大鼠头部或暴露皮层上的可选择位置产生精确且可测量的影响。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。健康相关性：加深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。由完整颅骨撞击引起的创伤性脑损伤 (TBI) 是最常见的头部损伤形式。关于严重、震荡和亚震荡事件的长期影响，尚有一些悬而未决的问题。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。啮齿类动物脑损伤模型很常见，但损伤装置的功能有限，效果差异很大，并且影响参数仍然不明确。这些缺陷限制了研究人员重复他人工作和定义神经元损伤病因的能力。第一阶段的结果：目标 1：构建原型立体定位配件，向大鼠或小鼠施加冲击性神经创伤。该设备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入深度和速度。立体定位装置的线性和角度定位功能控制撞击的位置和方向。头部固定部件经过修改，可以牢固地支撑头部，同时分散反作用力。目标 2：使用新颖的冲击位置和方向，确认该设备在啮齿动物模型中产生可重复伤害的能力。进行了一项重点研究，以调查撞击位置和方向对幼年大鼠神经元变性的影响。新设备用于在位移和能量方面产生与重物跌落伤害相当的冲击力，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。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纳入基本设备中。冲击器将配备仪器来实时描述每个事件的特征。目标 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且完整的验证。 “受控皮质冲击”（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于复制先前研究中看到的行为变化。