Experimental modelling of human spinal cord injury: A model that crosses the species barrier and mimics the spectrum of human cytopathology

Abstract

Study design: Literature review and presentation of an experimental model of human spinal cord injury, (SCI). Objectives: Experimental designs seek to mimic and model the physical processes by which human SCI occurs and replicate the variety of chronic pathologies that characterize its long term effects. The variations in biological processes that are present between species have contributed to recent difficulties in generalizing experimental findings to the human condition. In this review, one finds: (1) a discourse on the pathological nature of the chronic human lesion, (2) a consideration of how the physical properties of soft tissue injury result in acute and chronic changes in the spinal substance, (3) a description of a device (ESCID) that is able to replicate and dynamically monitor physical indices of SCI as they take place in experimental models, and (4) a summary of how use of this device in different species has allowed the biomechanical descriptors of such injuries to be easily compared even in murine models. Setting: Ohio State University, Ohio, USA. Results: Careful attention to the details of injury device design has finally allowed a direct comparison of contusion-type injury models in the rat and mouse. Biomechanical outcomes with predictive capabilities have evolved that allow the investigator to create the range of pathologies seen in the human lesion even in these small vertebrates. The predictive cytopathology and our ability to manipulate the mouse genome will allow the testing of specific hypotheses related to cause and effect in experimental spinal cord injuries. Since the biomechanics, pathology, and chronic outcomes appear to be similar to those seen in the human, these animal models should facilitate rapid progress in the design of human therapeutics. Conclusions: Biomechanics of certain elements of experimental spinal injury are surprisingly accurate descriptors of acute and chronic pathologies in the spinal cord. This tenet applies across species and has often allowed more accurate design of clinical trials in the past few decades. As molecular approaches to this problem evolve, the use of species with known genomes appear warranted. Models that take advantage of these approaches are likely to produce innovations that quicken the pace of human trial strategies.