A simple, inexpensive and easily reproducible model of spinal cord injury in mice: Morphological and functional assessment

Marques, Suelen Adriani; Garcez, Valéria Ferreira; Bel, Elaine Aparecida Del; Martínez, Ana Maria Blanco

doi:10.1016/j.jneumeth.2008.10.015

Cited by 67 publications

(31 citation statements)

References 45 publications

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“…20 Use of a modified vascular clip in the mouse was also recently shown to be effective. 21 A spring-loaded clip has also been utilized to induce injury in the thoracic spine of pigs. 22 The advantages of clip compression are that it provides a compression-contusion model that is relatively inexpensive, generates SCI of varying severity and is adaptable for use in all regions of the spine.…”

Section: Clip Compressionmentioning

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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Section: Clip Compressionmentioning

confidence: 99%

Spinal cord injury models: a review

et al. 2014

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“…To date, the vast majority of spinal contusion models in the mouse have targeted thoracic levels, [3][4][5] and it was only very recently that the first mouse model of bilateral cervical contusion SCI was described by Aguilar and Steward. 6 Other available animal models of SCI include crushtype lesions, 7 medullar compressions, 8 and surgical tract axotomies. [9][10][11][12][13] In particular, hemisection models at a high cervical level (C2) have been useful for studying the plasticity, recovery, and repair of descending innervation of the phrenic nucleus, and notably were used to characterize the crossed-phrenic pathway in both mice 13 and rats.…”

Section: Introductionmentioning

confidence: 99%

Degeneration of Phrenic Motor Neurons Induces Long-Term Diaphragm Deficits following Mid-Cervical Spinal Contusion in Mice

Nicaise

Putatunda

Hala

et al. 2012

Journal of Neurotrauma

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A primary cause of morbidity and mortality following cervical spinal cord injury (SCI) is respiratory compromise, regardless of the level of trauma. In particular, SCI at mid-cervical regions targets degeneration of both descending bulbospinal respiratory axons and cell bodies of phrenic motor neurons, resulting in deficits in the function of the diaphragm, the primary muscle of inspiration. Contusion-type trauma to the cervical spinal cord is one of the most common forms of human SCI; however, few studies have evaluated mid-cervical contusion in animal models or characterized consequent histopathological and functional effects of degeneration of phrenic motor neuron-diaphragm circuitry. We have generated a mouse model of cervical contusion SCI that unilaterally targets both C4 and C5 levels, the location of the phrenic motor neuron pool, and have examined histological and functional outcomes for up to 6 weeks post-injury. We report that phrenic motor neuron loss in cervical spinal cord, phrenic nerve axonal degeneration, and denervation at diaphragm neuromuscular junctions (NMJ) resulted in compromised ipsilateral diaphragm function, as demonstrated by persistent reduction in diaphragm compound muscle action potential amplitudes following phrenic nerve stimulation and abnormalities in spontaneous diaphragm electromyography (EMG) recordings. This injury paradigm is reproducible, does not require ventilatory assistance, and provides proof-of-principle that generation of unilateral cervical contusion is a feasible strategy for modeling diaphragmatic/respiratory deficits in mice. This study and its accompanying analyses pave the way for using transgenic mouse technology to explore the function of specific genes in the pathophysiology of phrenic motor neuron degeneration and respiratory dysfunction following cervical SCI.

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“…All surgical procedures and postoperative animal care were carried out in accordance with the Guide for the Care and Use of Laboratory Animals (National Research Council, 1996, USA) and was approved by the Animal Use and Care Committee of School of Medicine, Harbin Medical University. In accordance with the clip compression model described previously [27], all mice were anesthetized by intraperitoneal injection of 10% chloral hydrate (5 mL/kg) and then positioned on a cork platform. The skin was incised along the midline of the back, and the paravertebral muscles of the thoracic-level (T8-T10) vertebrae were dissected out.…”

Section: Animals and Spinal Cord Injurymentioning

confidence: 99%