Histopathological and Behavioral Characterization of a Novel Cervical Spinal Cord Displacement Contusion Injury in the Rat

Pearse, Damien D.; Lo, Thomas P.; Cho, K. S.; Lynch, Michael P.; Garg, M. S.; Marcillo, Alexander; Sanchez, Andre; Cruz, Yolanda; Dietrich, W. Dalton

doi:10.1089/neu.2005.22.680

Cited by 129 publications

(115 citation statements)

References 66 publications

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“…Behavior was not assessed in the present study. However, it has been reported that rats with contusive SCI at their C5 segment improved to weight-supported locomotion in the open field between the first and second week post-SCI (Pearse et al, 2005). Rats with contusive SCI at their C4-5 segments also were unable to perform a pellet retrieval task until at least 3 weeks afterward due to a lack of limb elevation, shoulder extension, and elbow extension (Schrimsher and Reier, 1993).…”

Section: Discussionmentioning

confidence: 99%

Loss and spontaneous recovery of forelimb evoked potentials in both the adult rat cuneate nucleus and somatosensory cortex following contusive cervical spinal cord injury

Onifer

Nunn

Decker

et al. 2007

Experimental Neurology

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Varying degrees of neurologic function spontaneously recovers in humans and animals during the days and months after spinal cord injury (SCI). For example, abolished upper limb somatosensory potentials (SSEPS) and cutaneous sensations can recover in persons post-contusive cervical SCI. To maximize recovery and the development/evaluation of repair strategies, a better understanding of the anatomical locations and physiological processes underlying spontaneous recovery after SCI is needed. As an initial step, the present study examined whether recovery of upper limb SSEPs after contusive cervical SCI was due to the integrity of some spared dorsal column primary afferents that terminate within the cuneate nucleus and not one of several alternate routes. C5-C6 contusions were performed on male adult rats. Electrophysiological techniques were used in the same rat to determine forelimb evoked neuronal responses in both cortex (SSEPS) and the cuneate nucleus (terminal extracellular recordings). SSEPs were not evoked 2 days post-SCI but were found at 7 days and beyond, with an observed change in latencies between 7 and 14 days (suggestive of spared axon remyelination). Forelimb evoked activity in the cuneate nucleus at 15 but not 3 days post-injury occurred despite dorsal column damage throughout the cervical injury (as seen histologically). Neuroanatomical tracing (using 1% unconjugated cholera toxin B subunit) confirmed that upper limb primary afferent terminals remained within the cuneate nuclei. Taken together, these results indicate Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

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Section: Discussionmentioning

confidence: 99%

Loss and spontaneous recovery of forelimb evoked potentials in both the adult rat cuneate nucleus and somatosensory cortex following contusive cervical spinal cord injury

Onifer

Nunn

Decker

et al. 2007

Experimental Neurology

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“…3 As with the MASCIS and IH devices, the OSU impactor has recently been used to induce injury in the cervical spine of the rat. 15 A limitation of the device is that it is sometimes challenging to determine the zero distance for the impactor as the spinal cord and cerebrospinal fluid is displaced slightly when initially loaded.…”

Section: Infinite Horizon (Ih) Impactormentioning

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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“…Verify the injury visually by bruising on the spinal cord ( Figure. 5E, arrow) and check the injury parameters provided by the NYU software 12,17 ( Figure 6). 7.…”

Section: Stabilizing the Vertebrae And Performing The Impact Injurymentioning

confidence: 99%

“…Positional shifting of the target spine during contact between the impact plunger and the spinal cord alters the resultant injury force. The cervical contusive SCI model is a more clinically relevant model than other forms of SCI, as approximately 50% of human SCI cases occur at this level 8 , and several SCI studies have been performed using animal cervical injury models [9][10][11][12][13][14] . Although contusive SCI models often utilize some form of stabilization by clamping the spinal processes anterior and posterior to the injury site, this preparation is difficult for producing cervical SCI.…”

Section: Introductionmentioning

confidence: 99%

A Novel Vertebral Stabilization Method for Producing Contusive Spinal Cord Injury

Walker

Zhang

et al. 2015

JoVE

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Clinically-relevant animal cervical spinal cord injury (SCI) models are essential for developing and testing potential therapies; however, producing reliable cervical SCI is difficult due to lack of satisfactory methods of vertebral stabilization. The conventional method to stabilize the spine is to suspend the rostral and caudal cervical spine via clamps attached to cervical spinous processes. However, this method of stabilization fails to prevent tissue yielding during the contusion as the cervical spinal processes are too short to be effectively secured by the clamps (Figure 1). Here we introduce a new method to completely stabilize the cervical vertebra at the same level of the impact injury. This method effectively minimizes movement of the spinal column at the site of impact, which greatly improves the production of consistent SCIs. We provide visual description of the equipment (Figure 2-4), methods, and a step-by-step protocol for the stabilization of the cervical 5 vertebra (C5) of adult rats, to perform laminectomy ( Figure 5) and produce a contusive SCI thereafter. Although we only demonstrate a cervical hemi-contusion using the NYU/MASCIS impactor device, this vertebral stabilization technique can be applied to other regions of the spinal cord, or be adapted to other SCI devices. Improving spinal cord exposure and fixation through vertebral stabilization may be valuable for producing consistent and reliable injuries to the spinal cord. This vertebral stabilization method can also be used for stereotactic injections of cells and tracers, and for imaging using two-photon microscopy in various neurobiological studies.

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Histopathological and Behavioral Characterization of a Novel Cervical Spinal Cord Displacement Contusion Injury in the Rat

Cited by 129 publications

References 66 publications

Loss and spontaneous recovery of forelimb evoked potentials in both the adult rat cuneate nucleus and somatosensory cortex following contusive cervical spinal cord injury

Loss and spontaneous recovery of forelimb evoked potentials in both the adult rat cuneate nucleus and somatosensory cortex following contusive cervical spinal cord injury

Spinal cord injury models: a review

A Novel Vertebral Stabilization Method for Producing Contusive Spinal Cord Injury

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