Animal Models Used in Spinal Cord Regeneration Research

Kwon, Brian K.; Oxland, Tom R; Tetzlaff, Wolfram

doi:10.1097/00007632-200207150-00005

Cited by 184 publications

(118 citation statements)

References 64 publications

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“…39 Thus, in order to assure that natural or intervention-based recovery is truly determined by the Spinal cord injury models T Cheriyan et al transection, the cord should be retransected to observe loss of regained function. 40 Transection models, being relatively easy to perform, have been investigated in a variety of animals including rats, mice, cats, dogs and primates. 41 Partial transection Partial transection, unilateral transection and hemisection of the spinal cord all refer to the process of selectively lesioning the spinal cord (Figures 3a-c).…”

Section: Full Transectionmentioning

confidence: 99%

“…42 In addition, given that hemisection results in a less severe injury than complete transection, postoperative animal care is easier. 40 However, it is more difficult to inflict a consistent injury with a partial transection model, and it can be difficult to determine whether the target tract is completely severed. This concern can be addressed with retrograde labeling or, more recently, somatosensory evoked potentials.…”

Section: Full Transectionmentioning

confidence: 99%

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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: Full Transectionmentioning

confidence: 99%

Section: Full Transectionmentioning

confidence: 99%

Spinal cord injury models: a review

et al. 2014

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“…Rat model, as the most consistently studied and standardized model, has received much attention by scientists for the assessment of locomotive performance and to determine the functional consequences of the initial injury, spontaneous function recovery and the efficacy of therapeutic strategies. [1][2][3] Currently, a number of assessment methods, such as BBB locomotor rating scale, 4,5 modified Tarlov scoring system, 6 grid-walk test, 7 narrow beam test 8 and inclined plane test, 9 have been developed to evaluate the movement recovery after SCI. However, it is believed that these qualitative methods have been designed to assess mainly fine locomotor skills owing to descending fiber regeneration, which results in apparently lack of spontaneous recovery in spinal rodents.…”

Section: Introductionmentioning

confidence: 99%

Observation of locomotor functional recovery in adult complete spinal rats with BWSTT using semiquantitative and qualitative methods

Zhang

Shurong

et al. 2007

Spinal Cord

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Study design: Experimental rat model of spinal cord transection. Setting: China rehabilitation research center. Objective: To investigate locomotor functional recovery in spinal rats with BWSTT using semiquantitative and qualitative methods. Methods: Five-day postoperative (dpo), adult female complete spinal rats (at T 8 level) received 40 days of body weight-supported treadmill training (BWSTT). Signs of functional recovery were examined with average combined scores (ACOS) and Basso Beattie and Bresnahan (BBB) scales at different time points. Results: At 1-dpo, none of the spinal rats exhibited hindlimb movements. The spinal rats displayed functional progress with time, but the rare could recover to full weight-bearing hindlimb at 45-dpo. BBB and ACOS scores in the BWSTT group obtained better scores than those in the spinal cord injury (SCI) group at 30-and 45-dpo. Furthermore, all BBB and ACOS scores of spinal rats reached statistical significance between 7-and 30-dpo, and between 15-and 30-dpo. However, only ACOS but not BBB scores in the SCI and BWSTT groups showed statistics differences between 15-and 45-dpo, and between 30-and 45-dpo. The Spearman correlation coefficients of BBB and ACOS scores were 0.913 and 0.972 for the SCI and BWSTT groups, respectively. Conclusions: The results confirmed the existence of partial spontaneous hindlimb functional recovery in adult chronically spinal cord-transected rats, and that BWSTT can improve motor performance. In addition, our study suggests that qualitative and semiquantiative methods are strongly correlated with locomotor recovery in spinal rats, and the latter may be more sensitive in reflecting minor variance at different time points.

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“…1 These models have allowed the study of potential new treatments and approaches to reduce secondary cellular damage and scar formation or to increase neuronal regeneration and reconnection. 2 Most recently, efforts have been made to develop murine models of SCI because of the ability to use genetically engineered animals and additional molecular tools in neurotrauma research.…”

Section: Introductionmentioning

confidence: 99%

Semiquantitative assessment of hindlimb movement recovery without intervention in adult paraplegic mice

Guertin

2004

Spinal Cord

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Study design: Experimental laboratory investigation of hindlimb movement recovery in chronic paraplegic mice. Objectives: Development of an assessment method to discriminatively quantify motor and locomotor-like movements of paraplegic mice. Setting: Laval University Medical Center, Quebec, Canada. Methods: Signs of 'functional recovery' were examined in open-field condition during 1 month in adult mice with a complete spinal cord transection at the low-thoracic level. Results: None of the mice exhibited hindlimb movements after spinalization. At 7 days, 33% of them displayed weak nonbilaterally alternating movements (NBA). At 14 days, increased NBA were observed and the first bilaterally alternating movements (BA) in 10% of the mice. A progressive increase of movement frequency and amplitude was found after 2-3 weeks. By the end of the month, 86% displayed mixed NBA and BA. However, none of them recovered the ability to stand or bear their own weight with the hindlimbs. Conclusion: This study reports signs of partial hindlimb movement recovery in chronic paraplegic mice and provides evidence of plasticity in sublesional circuits of neurons occurring in the absence of inputs from the brain, locomotor training or pharmacological treatment. This assessment method can be used to characterize hindlimb movements in complete spinal cord transected mice tested in open-field condition.

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Animal Models Used in Spinal Cord Regeneration Research

Abstract: Animal models will continue to play a critical role in the development of experimental therapies for spinal cord injuries. Both sharp and blunt spinal cord injury paradigms have unique characteristics that make them useful in addressing slightly different neurobiologic problems.

Cited by 184 publications

References 64 publications

Spinal cord injury models: a review

Spinal cord injury models: a review

Observation of locomotor functional recovery in adult complete spinal rats with BWSTT using semiquantitative and qualitative methods

Semiquantitative assessment of hindlimb movement recovery without intervention in adult paraplegic mice

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