ANIMAL MODELS OF INJURY

Director: Dr. Barbara Bregman and Dr. Jean Wrathall

Studies to define the mechanisms underlying plasticity require the use of specific CNS injury models in rats or mice. In both instances, the expertise is best provided by individuals through a shared resource, so that individual investigators can make use of the techniques and approaches without having to incur the expense of building the expertise and acquiring the equipment in their individual laboratories. Through this NCARRN, these resources will be available to investigators participating in this program through sabbaticals, through the pilot grants project, and will be available as a national resource for individuals interested in studies to define the mechanisms underlying CNS plasticity and recovery of function after spinal cord injury. Drs. Barbara Bregman and Jean Wrathall co-direct the injury models and behavioral analysis components of the NCARRN.

This core offers expertise in the following CNS injury models: spinal cord injury (surgical hemisection, transection, contusion injury, surgical rhizotomy, sciatic nerve lesions, fluid percussion head injury, and stroke. Each of these techniques are well established in one or more of the participating laboratories. For NCARRN participants requiring short term use of the injury models, this core will generate the animals needed for pilot studies. The core will also provide in-depth training in injury models (generation, post-operative care, data analysis and interpretation) for those individuals and projects requiring long term use of injury models.

Spinal Cord Injury Models: Currently there are a variety of specific spinal cord injury models available for analysis of anatomical reorganization recovery of function after CNS injury. There are surgical approaches using specific spinal cord surgical lesions to damage specific pathways, for example, a hemisection model injuring half of the pathways within the spinal cord, leaving intact the contralateral pathways as controls. Specific spinal cord injury models can also destroy specific pathways, for instance, the sensory pathways in the dorsal columns or descending pathways within the lateral funiculus, for example. Spinal cord lesions can also be made at a variety of different levels within the neuraxis: high cervical injury, mid-thoracic or lumbar levels. In the spinal cord injury models there are also complete spinal cord transection models which interrupt completely all of the pathways projecting to the spinal pattern generators for locomotion. This core facility provides both the expertise to make the lesions and the required expertise in specialized animal care after spinal cord injury. In addition to spinal cord lesions, this core will provide the expertise for sciatic nerve lesions and dorsal rhizotomy injury for those projects requiring such specialized lesions.

Head Injury and Stroke Models: In addition to the well-established spinal cord injury models, there are a number of head injury models available as part of the core resources within this network. A very well-established injury model that mimics that of stroke in humans is a photochemical injury in which Rose Bengal dye is injected into the blood stream. The area of interest to be damaged is then exposed surgically and the lesion created by using photo-illumination. This leads to very precise injury models that mimic that seen in stroke. Traumatic brain injury (TBI) models are also well-established as part of this core. The head injury fluid percussion model allows a traumatic closed head injury in animals. The injury device is available in the Faden laboratory and will be available to all NCARRN participants as part of this Core. In addition to animal head injury models, we also have very well-established as part of this network models of head injury in which cultured neurons are exposed to fluid percussion injury similar to that in the whole animal. The investigators participating within this network will have access to facilities allowing them to address scientific questions of interest from both whole animal and tissue culture approaches.

Motor Behavioral Analysis
One of the unique resources this NCARRN provides is a very extensive and experienced network of equipment and expertise providing behavioral analysis of recovery of motor function after central nervous system injury. The behavioral analysis components include opportunities to learn the techniques associated with spontaneous open-field locomotor function (BBB, CBS) and skilled locomotion (over-ground, treadmill, grid, etc.). In studies of recovery of function it is essential to be able to distinguish between the functions that are lost as a result of the injury and those that recover. It is important that the protocols for analyzing and training the animals in studies of recovery of function are able to distinguish clearly between the inability to use a body part versus the reluctance to use it. There are a variety of resources available to analyze recovery of function after spinal cord injury, traumatic brain injury and stroke. We have in place, as part of this NCARRN, behavioral facilities to allow individual investigators to study recovery of locomotion, including the study of overground locomotion, treadmill locomotion, and locomotion over variety of runways that require accurate foot placement. In addition, we have facilities to study skilled motor function such as reaching.

A number of important resources are available to NCARRN investigators who are investigating neural plasticity through animal-based injury models.Kinematics of locomotion (joint angles, swing: stance ratio, hypermetria, hypometria, etc.) can be studied by quantitatively measuring the angles of hindlimb movement recorded on the video tapes. With the Peak Performance Motus Movement Analysis System, we are able to feed the video image into the computer, store the image, and measure the joint angles, limb excursion, etc. directly. A?Catwalk gait analysis system? is also available for locomotionn analysis. This system utilizes fiber optic technology with sophisticated software to perform footprint and force analysis. The animals run on a glass surface that has light shining through it. As the animal places its paw on the surface, the light is deflected into a mirror that reflects it to a camera. The camera transmits the information into a computer that reconfigures and analyzes it. Different forces produce different reflected colors; therefore the greater the weight support, the brighter the color of footprint. Furthermore, the computer reconstructs the footprints into a trail. From that trail, measures of rotation stride length and base of support can be made.