Cell Death, Repair, and Recovery of Function after Spinal Cord Contusion Injuries in Rats

Abstract

Many attempts to model human spinal cord injury in animals have been made through the years. Recently, some consensus has been reached in terms of the goals of such models. They need to be reliable, consistent, and reproducible from laboratory to laboratory (1). They need to replicate some of the important pathologic features of human spinal cord injury (SCI). The models should allow assessment of some of the mechanistic features of damage and recovery after injury. When large treatment trials are needed, the models need to be efficient, and outcome measures need to be relatively simple. These considerations have led to a number of new models in rats, cats, and other species over the past several years. Our laboratory has worked to develop models in the rat (2–8) and most recently, we have joined a consortium of other laboratories to help standardize a weight-drop model with chronic neurologic and histologic outcome measures (3,9,10) The Multicenter Animal Spinal Cord Injury Study (MASCIS) was formed to combine the expertise of multiple laboratories, to provide for interlaboratory reproducibility in assessing preclinical treatments for SCI (MASCIS was initiated by Dr. Wise Young). As a result of this effort, and the work of many other laboratories, it is now possible to predict outcomes and test therapies efficiently in contusion injury models. The lesions produced by the MASCIS contusion device and by other similar models, for example, the Ohio State University electromechanical model (7,11,12), are characterized by the development of central hemorrhagic necrosis that spreads radially, as well as rostrocaudally over time. The end result is an ellipsoidal, loculated cystic cavity or cell-filled injury site (7,8,13–15). Contusion lesions in rats respond to early pharmacologic interventions similar to human cord injuries (6,16–18), suggesting that this model is useful for assessing clinical treatments. Some of the features of these lesions are shown in Figure 1.