Stereotaxic Accessory for Reproducible Neurotrauma

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.