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

Choo, Anthony M.; Liu, Jie; Liu, Zhuowei; Dvorak, Marcel F.; Tetzlaff, Wolfram; Oxland, Thomas R.

doi:10.1016/j.jneumeth.2009.04.007

Cited by 77 publications

(60 citation statements)

References 51 publications

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“…Amongst these injury models, contusion and compression injuries bestinjury severity is dictated by the height from which the weight is dropped. In contrast, in the Ohio State University (OSU) impactor and the multimechanism injury system designed by Choo et al (2009), the maximum displacement of the spinal cord is determined, and the force imparted to the cord is then measured. The IH impactor is distinct in that the user dictates the force applied, and then the displacement is measured.…”

Section: Discussionmentioning

confidence: 99%

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A Contusive Model of Unilateral Cervical Spinal Cord Injury Using the Infinite Horizon Impactor

Lee

Streijger

Tigchelaar

et al. 2012

JoVE

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While the majority of human spinal cord injuries occur in the cervical spinal cord, the vast majority of laboratory research employs animal models of spinal cord injury (SCI) in which the thoracic spinal cord is injured. Additionally, because most human cord injuries occur as the result of blunt, non-penetrating trauma (e.g. motor vehicle accident, sporting injury) where the spinal cord is violently struck by displaced bone or soft tissues, the majority of SCI researchers are of the opinion that the most clinically relevant injury models are those in which the spinal cord is rapidly contused. 1 Therefore, an important step in the preclinical evaluation of novel treatments on their way to human translation is an assessment of their efficacy in a model of contusion SCI within the cervical spinal cord. Here, we describe the technical aspects and resultant anatomical and behavioral outcomes of an unilateral contusive model of cervical SCI that employs the Infinite Horizon spinal cord injury impactor.Sprague Dawley rats underwent a left-sided unilateral laminectomy at C5. To optimize the reproducibility of the biomechanical, functional, and histological outcomes of the injury model, we contused the spinal cords using an impact force of 150 kdyn, an impact trajectory of 22.5°(animals rotated at 22.5°), and an impact location off of midline of 1.4 mm. Functional recovery was assessed using the cylinder rearing test, horizontal ladder test, grooming test and modified Montoya's staircase test for up to 6 weeks, after which the spinal cords were evaluated histologically for white and grey matter sparing.The injury model presented here imparts consistent and reproducible biomechanical forces to the spinal cord, an important feature of any experimental SCI model. This results in discrete histological damage to the lateral half of the spinal cord which is largely contained to the ipsilateral side of injury. The injury is well tolerated by the animals, but does result in functional deficits of the forelimb that are significant and sustained in the weeks following injury. The cervical unilateral injury model presented here may be a resource to researchers who wish to evaluate potentially promising therapies prior to human translation. Video LinkThe video component of this article can be found at

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Section: Discussionmentioning

confidence: 99%

“…8 In our study, functional deficits were assessed with the horizontal ladder test, cylinder rearing test, grooming test and Montoya staircase test. Both the horizontal ladder test and cylinder rearing are valuable assessments after cervical injury models.…”

Section: Discussionmentioning

confidence: 99%

A Contusive Model of Unilateral Cervical Spinal Cord Injury Using the Infinite Horizon Impactor

Lee

Streijger

Tigchelaar

et al. 2012

JoVE

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“…The geometric variable most relevant to AP cervical dislocation is CPD, and changes in this variable have been assessed during simulated frontal and rear impacts (Ito et al, 2004;Ivancic et al, 2006). Using 3-month old Sprague-Dawley rats, Choo et al (2009) classified a 2.6-mm dislocation as moderate-to-severe with a mortality rate of 10%. The current results from Fisher 344 rats indicate that a 2.6-mm C4/C5 dislocation would be 85.8% of CPD for 3-month olds (the age most commonly used for experimental SCI studies), but only 73.0% and 68.8% of CPD for 12-18-and 30-month olds, respectively.…”

Section: Discussionmentioning

confidence: 99%

Effects of Advanced Age on the Morphometry and Degenerative State of the Cervical Spine in a Rat Model

Laing

Cox

Tetzlaff

et al. 2011

The Anatomical Record

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Aging causes changes in the geometry of the human cervical spine that may influence the tissue response to applied loads. Rat models are often used to study spinal cord injuries (SCI) and have the potential to enhance our understanding of the effect of age on SCI. The goal of this study was to characterize the morphometry and degenerative state of the cervical spine in Fisher 344 rats, and to determine the influence of age on these variables. Fifteen rats were split into three age groups: young adult (3 months of age), aged (12-18 months) and geriatric (30 months). Following tissue harvest we used a lCT scanner to image the cervical and upper thoracic spine from each specimen. Analysis software was used to measure variables including canal pinch diameter (the most rostral point on the dorsal aspect of a vertebral body to the most caudal aspect of the lamina on the immediately rostral vertebra), vertebral canal depth, width, and area, vertebral body height, depth, width, and area, and intervertebral disc thickness. Orthopaedic surgeons used midsagittal images to rate the degenerative state of the intervertebral discs. For all measures except disc thickness there was a significant increase (mean (SD) ¼ 15.0 (9.7)%) for the aged compared to young specimens (P < 0.05). There were significant differences between the aged and geriatric specimens for only vertebral body depth (P ¼ 0.016) and area (P ¼ 0.020). Intervertebral disc degeneration was significantly greater on the ventral aspect of the spinal column (P < 0.001), with a trend toward increased degeneration in the geriatric specimens (P ¼ 0.069). The results suggest that agerelated morphometric differences may need to be accounted for in experimental aging models of SCI in rats. Anat Rec, 294:1326Rec, 294: -1336Rec, 294: , 2011. V V C 2011 Wiley-Liss, Inc.

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“…35 The device is capable of providing feedback on cord displacement or force transmitted following injury. The UBC device uses clamps that wedge beneath the transverse processes against the lateral masses of the vertebrae with firm support, allowing researchers to accelerate the device components to high velocities (up to 1 m s À1 ) without vertebral slippage during injury.…”

Section: University Of British Columbia (Ubc) Multimechanism Devicementioning

confidence: 99%

“…Choo et al 35 described a similar procedure to produce an anterior dislocation model where the vertebra is dislocated dorsally. The model attempts to closely reproduce the anterior fracture-dislocation injuries that are more commonly seen than later dislocations.…”

Section: Dislocation Modelmentioning

confidence: 99%

Spinal cord injury models: a review

et al. 2014

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Background: Animal spinal cord injury (SCI) models have proved invaluable in better understanding the mechanisms involved in traumatic SCI and evaluating the effectiveness of experimental therapeutic interventions. Over the past 25 years, substantial gains have been made in developing consistent, reproducible and reliable animal SCI models. Study design: Review. Objective: The objective of this review was to consolidate current knowledge on SCI models and introduce newer paradigms that are currently being developed. Results: SCI models are categorized based on the mechanism of injury into contusion, compression, distraction, dislocation, transection or chemical models. Contusion devices inflict a transient, acute injury to the spinal cord using a weight-drop technique, electromagnetic impactor or air pressure. Compression devices compress the cord at specific force and duration to cause SCI. Distraction SCI devices inflict graded injury by controlled stretching of the cord. Mechanical displacement of the vertebrae is utilized to produce dislocation-type SCI. Surgical transection of the cord, partial or complete, is particularly useful in regenerative medicine. Finally, chemically induced SCI replicates select components of the secondary injury cascade. Although rodents remain the most commonly used species and are best suited for preliminary SCI studies, large animal and nonhuman primate experiments better approximate human SCI. Conclusion: All SCI models aim to replicate SCI in humans as closely as possible. Given the recent improvements in commonly used models and development of newer paradigms, much progress is anticipated in the coming years. Spinal Cord (2014) 52, 588-595; doi:10.1038/sc.2014.91; published online 10 June 2014 INTRODUCTIONSpinal cord injury (SCI) models have proved indispensible not only for investigating the efficacy of therapeutic interventions but also for better understanding the molecular pathways involved. SCI models have evolved significantly over the past century since Allen developed the first weight-drop contusion model in 1911. 1 SCI models aim to recreate features of human SCI as closely as possible. These models vary in terms of the animal utilized, site of injury infliction and injury mechanism.Rats are used most commonly in preliminary studies as they are relatively inexpensive, readily available and have demonstrated similar functional, electrophysiological, and morphological outcomes to humans following SCI. 2 Mice are particularly useful for genetic studies. 3 Nonhuman primate SCI models-including marmosets, macaques and squirrel monkeys-better approximate human SCI than rodent models, and they accommodate assessment of multiple recovery variables and rehabilitative therapy. 4 New world primates like marmosets confer advantages over old world primates as they are smaller, easier to handle, have a higher breeding efficiency and can be bred in experimental colonies. SCI models that incorporate large animals-such as pigs or dogs-can also be used when it is important for furth...

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

Cited by 77 publications

References 51 publications

A Contusive Model of Unilateral Cervical Spinal Cord Injury Using the Infinite Horizon Impactor

A Contusive Model of Unilateral Cervical Spinal Cord Injury Using the Infinite Horizon Impactor

Effects of Advanced Age on the Morphometry and Degenerative State of the Cervical Spine in a Rat Model

Spinal cord injury models: a review

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