Traumatic Spinal Cord Injury Produced by Controlled Contusion in Mouse

Abstract

Previous work from this laboratory has described a rat spinal cord injury (SCI) model in which the mid-thoracic spinal cord is subjected to a single rapid and calibrated displacement at the site of a dorsal laminectomy. Injury is initiated at the tip of a vertical shaft driven by an electromagnetic shaker. Transducers arranged in series with the shaft record the patterns of displacement and force during the impact sequence. In the present study, this device and the relevant surgical procedures were adapted to produce a spinal contusion injury model in laboratory mice. The signal generator for the injury device has also been converted to a computer-controlled interface to permit extension of the model to other laboratories. Mice were subjected to SCI across a range of severities by varying the amplitude of displacement and the magnitude of measured preload force on the dural surface. A moderate injury produced by displacement of 0.5 mm over 25 msec resulted in initial paralysis and recovery of locomotion with chronic deficits in hindlimb function. The magnitude of the peak force, impulse, power, and energy generated at impact were correlated with behavioral outcome at 1 day postinjury, while peak displacement and impulse were the best predictors of behavioral outcome at 28 days postinjury. The shape of the force recording proved to be a highly sensitive measure of subtle variations in the spinal compartment that were otherwise difficult to detect in this small species. The results demonstrate that the electromagnetic spinal cord injury device (ESCID) can be used to produce a well-controlled contusion injury in mice. The unique features of controlled displacement and monitoring of the biomechanical parameters at the time of impact provide advantages of this model for reducing outcome variability. Use of this model in mice with naturally occurring and genetically engineered mutations will facilitate understanding of the molecular mechanisms of pathophysiology following traumatic spinal cord injury.

Diffusion Tensor Imaging at 3 Hours after Traumatic Spinal Cord Injury Predicts Long-Term Locomotor Recovery

“…The mice were anesthetized with a mixture of ketamine (80 mg=kg) and xylazine (10 mg=kg) intraperitoneally. A modified OSU impacting device (1.3-mm-diameter round tip, 0.2 m=sec impact speed) was employed for contusion injury ( Jakeman et al, 2000;Kim et al, 2009b). Mice received 0.6-, 0.7-, 0.8-, or 0.9-mm (n ¼ 8 for each group) contusive SCIs with a bipolar electromagnetic wave form after dorsal laminectomy at the T8 and T9 vertebral level.…”

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

“…The mouse therefore can become a major focus of injury modeling in the foreseeable future. 16,33,34 The basic injury device (ESCID-2000) utilizes an electromagnet to produce a rapid, single impact spinal cord contusion. The electromagnet is controlled via computer interface using commercially available hardware/software that precipitates the impact sequence.…”

“…The importance of these critical procedures has been discussed elsewhere. 34 A simpli®ed diagram of the injury device is included here to illustrate design principles (Figures 1 and 2). As illustrated, both touch ( Figure 1B) and injury (hit, Figure 2A) signals are generated using the Labview Software (National Instruments) on a conventional PC.…”

“…We have shown previously that distinct histopathological outcome measures can be obtained by changing the amplitude of displacement in our injury models. 33,34 A similar three dimensional analysis will provide the most sensitive measure of the e ects of variations in biomechanical parameters as well as genetic or pharmacological manipulations on the pathology of the chronic lesion.…”

Neural Stem Cell Transplantation in Experimental Contusive Model of Spinal Cord Injury

“…The Ohio State University spinal cord research center has pursued the technological challenge of a device that can be used to induce a particular compression of the spinal cord with parameters of impact controlled by a computer 9 . This was originally designed for use with rats; later it was modified to apply towards mice 10 . The advantages of this kind of approach are that the biomechanics of injury can be studied more in depth and the parameters of injury can be defined in a more complete manner in order to obtain a reproducible experimental model, therefore allowing more precise evaluation of the effects of tested treatments on the functional recovery process.…”