Summary Statement

The mechanism of spinal cord injury varies across the human population and this may be important for the development of effective therapies. Therefore, detailed understanding of how variables such as impact velocity and depth affect cord tissue damage is important.

Purpose: Recent studies have shown differences in short term spinal cord pathology between spinal column injury mechanisms, such as contusion and fracture-dislocation. Such differences may exist at longer time points, and thus survival studies are needed in the dislocation models. A more in-depth characterization of the dislocation model is needed for development of a mild-moderate cervical spine dislocation model in a rat that is suitable for survival studies. Specifically, our objective in this study was to determine the dislocation displacement that produces initial spinal column failure in a Sprague-Dawley rat model and to validate a consistent injury at the desired dislocation in-vitro and in-vivo.

Method: For the dislocation model, the dorsal ligaments and facets at C4–C5 were removed to mimic the type of posterior element fracture and ligament injury commonly seen in a bilateral fracture-dislocation. C3 and C4 were clamped together and held stationary while the clamp holding C5 and C6 was connected to an electromagnetic actuator and displaced dorsally to produce the injury while force and displacement were recorded. Twenty-eight isolated cervical spine specimens of Sprague-Dawley rats were used to determine dislocation displacement at initial spinal column failure. The C4–C5 segment sustained dislocation (> 3mm) injury at 0.05mm/s (n=11), 100mm/s (n=4) and 1000mm/s (n=13). Initial spinal column failure was defined at with maximum force during the dislocation. A dislocation displacement of 1.4mm was applied to 7 isolated specimens and 4 anesthetized rats at 430mm/s. The spinal column failure was inspected up to 3 days after injury, as well as hemorrhage of spinal cord in-situ.

Results: The dislocation displacement at in-vitro spinal column failure was 0.95mm±0.32 and not significantly different among specimens at the three dislocation speeds. Under a dislocation displacement of 1.4mm, rupture of the C4–C5 disc occurred in all in-vitro (0.67mm±0.38) and in-vivo (0.65mm±0.17) cases. SCI hemorrhage at epicenter was observed in 3 of 4 cases.

Conclusion: The initial spinal column failure in an innovative SCI model occurs at displacement between 0.65mm and 0.95mm. Dislocation displacement of 1.4mm results in spinal column failure consistently and SCI hemorrhage, and may be suitable for survival studies.

Spinal cord damage was compared after an injury was inflicted by three clinically relevant mechanisms (contusion, dislocation, and distraction). A novel SCI multi-mechanism system has been developed. Central hemorrhage was common to all mechanisms. Increased membrane permeability was localized to the injury epicenter in contusion but spread further in distraction. Dislocation showed intermediate characteristics exhibiting both local neuronal losses at the epicenter and extended regions of membrane permeability. These preliminary observations suggest that distinct injury mechanisms result in differences in the primary damage of the spinal cord.

This work compared primary damage after spinal cord injury (SCI) inflicted by three clinically relevant mechanisms.

Different injury mechanisms result in regional differences in damage to the spinal cord.

Differences in acute damage may help guide targeted therapies following SCI.

At greater distances from the lesion, dextran was excluded from neuronal somata and in the white matter only distinct accumulation was seen at the Nodes of Ranvier. At the injury site, hemorrhage was common to all mechanisms although more diffuse in the distraction injuries. Increased membrane permeability was localized to the injury epicenter in contusion but spread further in distraction. Dislocation showed intermediate characteristics exhibiting both local neuronal losses at the epicenter and extended regions of permeability.

A novel SCI multi-mechanism system was developed which uses an electromagnetic actuator to permit the modeling of injuries along any direction. Dextran was infused into the cisterna magna 1.5 to 2 hours prior to injury in order to visualize increases in membrane permeability. Stereotaxic clamps were designed to rigidly hold the lower cervical vertebrae of deeply anaesthetized rats permitting displacements at speeds of 100cm/s. A range of displacements was used in this pilot series: 0.9 to 1.1mm contusion, 2 to 6mm dislocation and 3 to 8mm axial distraction. Animals were sacrificed at five minutes in order to analyse the primary injury. These preliminary observations suggest that distinct injury mechanisms result in regional differences in the primary damage of spinal cord gray and white matter.