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 e ects. The variations in biological processes that are present between species have contributed to recent di culties in generalizing experimental ®ndings to the human condition. In this review, one ®nds: (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 di erent 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 ®nally 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 speci®c hypotheses related to cause and e ect 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.

Wnts Are Expressed in the Spinal Cord of Adult Mice and Are Differentially Induced after Injury

“…8B); these differences may be associated with the different pathophysiological responses between species or even between strains of a given species. [46][47][48] Our results are in accord with the increasingly accepted role for Wnts in the modulation of fundamental aspects of the homeostasis and neuronal function of the adult CNS. 14,17,18,[49][50][51][52][53] In this line of thought, we provide supporting evidences of previous reports describing the expression of most Wnt ligands and receptors by PCR 39 and in situ hybridization analysis, 35 as well as a constitutive active b-catenin-mediated transcription in the dorsal horns and the central canal of the adult spinal cord of mice.…”

Pediatric Spinal Cord Injury in Infant Piglets: Description of a New Large Animal Model and Review of the Literature

“…The injury to the spinal cord found in our study in piglets with traumatic SCI is similar to that reported in other animal models of SCI, as well as in individuals with SCI (65)(66)(67). The pathology of complete or irreversible SCI invariably involves disruption of fiber tracts and spinal cord tissue through the thickness of the spinal cord, whereas incomplete SCI has intact fiber tracts passing through the injury zone.…”

Post-traumatic inflammation following spinal cord injury

“…30,31 The histopathology correlates positively with the biomechanical impact. 32 Lesion cavity Typically, the contusion SCI model is characterized by a central haemorrhagic necrosis that spreads radially and rostrocaudally, resulting in an ellipsoidal, loculated cystic cavity. The cavity is filled with macrophages and lined by activated astrocytes.…”