Characterization of a novel bidirectional distraction spinal cord injury animal model

Seifert, Jennifer L.; Bell, Jennifer E S; Elmer, Barbara; Sucato, Daniel J.; Romero, Mario I.

doi:10.1016/j.jneumeth.2011.02.003

Cited by 24 publications

(14 citation statements)

References 37 publications

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“…Interestingly, for a wide variety of spinal cord injury models (i.e. compression, dislocation, distraction, and hyperextension — Choo et al, 2007, 2008; Clarke et al, 2008; Lam et al, 2014; Li and Dai, 2009; Russell et al, 2012; Seifert et al, 2011), axonal injury has been shown to be most predominant in the ventral white matter. Such injury is not, however, necessarily limited to neurofilament compaction.…”

Section: Discussionmentioning

confidence: 99%

A novel closed-body model of spinal cord injury caused by high-pressure air blasts produces extensive axonal injury and motor impairments

Mar

Buttlar

et al. 2015

Experimental Neurology

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Diffuse axonal injury is thought to be the basis of the functional impairments stemming from mild traumatic brain injury. To examine how axons are damaged by traumatic events, such as motor vehicle accidents, falls, sports activities, or explosive blasts, we have taken advantage of the spinal cord with its extensive white matter tracts. We developed a closed-body model of spinal cord injury in mice whereby high-pressure air blasts targeted to lower thoracic vertebral levels produce tensile, compressive, and shear forces within the parenchyma of the spinal cord and thereby cause extensive axonal injury. Markers of cytoskeletal integrity showed that spinal cord axons exhibited three distinct pathologies: microtubule breakage, neurofilament compaction, and calpain-mediated spectrin breakdown. The dorsally situated axons of the corticospinal tract primarily exhibited microtubule breakage, whereas all three pathologies were common in the lateral and ventral white matter. Individual axons typically demonstrated only one of the three pathologies during the first 24 h after blast injury, suggesting that the different perturbations are initiated independently of one another. For the first few days after blast, neurofilament compaction was frequently accompanied by autophagy, and subsequent to that, by the fragmentation of degenerating axons. TuJ1 immunolabeling and mice with YFP-reporter labeling each revealed more extensive microtubule breakage than did βAPP immunolabeling, raising doubts about the sensitivity of this standard approach for assessing axonal injury. Although motor deficits were mild and largely transient, some aspects of motor function gradually worsened over several weeks, suggesting that a low level of axonal degeneration continued past the initial wave. Our model can help provide further insight into how to intervene in the processes by which initial axonal damage culminates in axonal degeneration, to improve outcomes after traumatic injury. Importantly, our findings of extensive axonal injury also caution that repeated trauma is likely to have cumulative adverse consequences for both brain and spinal cord.

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Section: Discussionmentioning

confidence: 99%

A novel closed-body model of spinal cord injury caused by high-pressure air blasts produces extensive axonal injury and motor impairments

Mar

Buttlar

et al. 2015

Experimental Neurology

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“…The UTA distractor (Figure 3b) 36 aimed to inflict a bidirectional distraction SCI as compared with the unidirectional injury generated by the UBC device. The UTA distractor used custom clips that are affixed securely to the vertebral body.…”

Section: University Of Texas At Arlington (Uta) Distractormentioning

confidence: 99%

“…It is relatively noninvasive, as a laminectomy is not performed, and computer software is able to record the force delivered to the spinal cord during the injury. 36 Mild, moderate and severe injury was assessed based on a distance distraction of 3, 5 and 7 mm, respectively. They used electrophysiological, behavioral and histological outcomes to measure the grade of injury.…”

Section: University Of Texas At Arlington (Uta) Distractormentioning

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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“…Many studies have investigated the injury conditions of the spinal cord 5,6,14,15 . Studies using living animal models measured the maximum elongation lengths of the spinal cord that could result in neurological signal changes 6,14 .…”

Section: Introductionmentioning

confidence: 99%

Investigation of in vivo three‐dimensional changes of the spinal canal after corrective surgeries of the idiopathic scoliosis

et al. 2021

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Objective To determine the three‐dimensional (3D) changes of the spinal canal length (SCL) after corrective surgeries and their association with the radiographic and clinical outcomes of idiopathic scoliosis patients. The length of the spinal cord has been demonstrated to be strongly correlated with the SCL. Understanding the changes in SCL could help determine the morphologic changes in the spinal cord to prevent spinal cord injury. Methods Twenty‐seven scoliotic patients' 3D spinal canal were investigated using computed tomography images. The SCL between the upper and lower end vertebrae (U/L‐EV) was measured at five locations. The radiographic parameters of each patient and the patient‐reported outcomes (PROs) scores were also collected. The correlations of the changes of the SCLs with the other factors were analyzed. Results The SCL between the U/L‐EV changed non‐uniformly at different locations. The post‐operative SCLs were significantly elongated by 7.5 ± 3.5 mm (6.0 ± 2.5%, P < .001) at the concave side and compressed by −2.6 ± 2.6 mm (−1.9 ± 1.9%, P < .001) at the convex side. The elongations of the SCL at the concave and posterior locations were correlated with the radiographic parameters including the pre‐operative main Cobb angles (r = .511, P = .006; r = .613, P = .001) and apical vertebral translation (AVT) (r = .481, P = .011; r = .684, P = .000). No PRO scores were found to correlate with the SCL changes. Conclusion The corrective surgeries elongated the spinal canal mainly at the concave side and compressed at the convex side. The main thoracic Cobb angle, the changes of AVT, and Cobb angles were moderately associated with the changes of the SCLs, but no PRO score was found to associate with the changes of the SCLs. The data could be instrumental for the improvement of corrective surgeries that are aimed to maximize the correction of scoliosis and minimize the negative effect on the spinal cord to prevent neurological complications.

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Characterization of a novel bidirectional distraction spinal cord injury animal model

Cited by 24 publications

References 37 publications

A novel closed-body model of spinal cord injury caused by high-pressure air blasts produces extensive axonal injury and motor impairments

A novel closed-body model of spinal cord injury caused by high-pressure air blasts produces extensive axonal injury and motor impairments

Spinal cord injury models: a review

Investigation of in vivo three‐dimensional changes of the spinal canal after corrective surgeries of the idiopathic scoliosis

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