Modeling spinal cord contusion, dislocation, and distraction: Characterization of vertebral clamps, injury severities, and node of Ranvier deformations

Abstract

Spinal cord contusion and transection models are widely used for studying spinal cord injury (SCI). Clinically, however, other biomechanical injury mechanisms such as vertebral dislocation and distraction frequently occur, but these injuries are difficult to produce in animals. We mechanically characterize a vertebral clamping strategy that enables the modeling of vertebral dislocation and distraction injuries – in addition to the standard contusion paradigm – in the rat cervical spine. These vertebral clamps have a stiffness of 83.6±18.9N/mm and clamping strength 64.7±10.2N which allows injuries to be modeled at high-speed (∼100cm/s). Logistic regression indicated that a moderate-to-severe injury, with an acute mortality rate of 10%, occurs at 2.6mm of C4/5 dorso-ventral dislocation and 4.1mm of rostro-caudal distraction between C4 and C5. Injuries produced by dislocation and distraction exhibited features of axonal damage that were absent in contusion injuries. We conducted morphometric analysis at the nodes of Ranvier using immunohistochemistry for potassium channels (Kv1.2) in the juxtaparanodal region. Following distraction injuries, elongated nodes of Ranvier were observed up to 4mm rostral to the lesion. In contrast, contusion injuries produced distortions in nodal geometry which were restricted to the vicinity of the lesion. The greatest deformations in node of Ranvier geometry occurred at the dislocation epicenter. Given the importance of white matter damage in SCI pathology, the distinctiveness of these injury patterns demonstrate that the dislocation and distraction injury models complement existing contusion models. Together, these three animal models span a broader clinical spectrum for more reliably gauging the potential human efficacy of therapeutic strategies.