Stereotaxic Accessory for Reproducible Neurotrauma

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.