Stereotaxic Accessory for Reproducible Neurotrauma

描述（由申请人提供）：由撞击完整颅骨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。神经元在撞击时的应变程度及其与随后的损伤和损害的关系尚不清楚。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。本申请旨在开发一种商用立体定位附件，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影响。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）控制撞击的能量、速度、力和位移;（3）测量这些参数以确认和表征创伤。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。 第一阶段的具体目标AIM 1：构建一个原型立体定位附件，以向大鼠或小鼠提供冲击性神经创伤。该装置将与大多数市售的立体定位装置兼容。将使用紧凑型电磁致动器向啮齿动物的头骨或大脑提供指定的力或压痕。立体定位装置的线性和角度定位能力将用于指定撞击的位置和方向。将修改头部固定部件，以牢固地支撑头部，同时将反作用力分布在主要撞击部位以外的位置。最初的原型将被设计用于小鼠或未成年大鼠。目的2：确认器械在啮齿动物模式下/使用新位置和冲击方向产生可重复损伤的能力。将进行一项紧凑的研究，以研究撞击位置和方向对幼年大鼠神经元变性的影响。先前的工作已经建立了3至30天大的大鼠闭合性头部损伤后通过兴奋性毒性和凋亡机制的细胞死亡模式。在以前的工作中，受伤是由重量下降引起的。申报器械将用于在力和能量方面产生等效冲击，但具有横向位置和方向。将确定并比较创伤后24小时的细胞死亡模式。 第二阶段的目标：将在第一阶段完成将紧凑型力、位移和加速度传感器集成到基本装置中。将对打入器和股骨头支撑组件进行器械化。

DESCRIPTION (provided by applicant): 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 injury and impairment, are little 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. This application is to develop a commercial 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 energy, velocity, force, and displacement of the impact; and (3) measure these parameters 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. Specific aims for Phase I AIM 1: Construct a prototype stereotaxic accessory to deliver impact neurotrauma to rat or mouse. The device will be compatible with most commercially available stereotaxic apparatus. A compact electromagnetic actuator will be used to provide a specified force or indentation to skull or brain of the rodent. The linear and angular positioning capabilities of the stereotaxic device will be used to specify the location and direction of impact. Head-holding components will be modified to support the head firmly while distributing reaction forces at locations other than the primary impact site. The initial prototype will be designed for work with the mouse or immature rat. AIM 2: Confirm the ability of the device to produce repeatable injury in a rodent mode/using novel location and direction of impact. A compact study will be performed to investigate the effect of impact location and direction on neuronal degeneration in the infant rat. Previous work has established patterns of cell death by excitotoxic and apoptotic mechanisms following closed-head injury in rats from 3 to 30 days old. In the prior work, injury was induced by weight-drop. The proposed device will be used to generate an equivalent impact in terms of force and energy but with a lateral location and direction. Patterns of cell death 24 hours post-trauma will be determined and compared. Objectives for Phase II: Incorporation of compact force, displacement, and acceleration sensors into the basic device will be accomplished in Phase I1. Both the impacter and the head support components will be instrumented.