Device use, locomotor training and the presence of arm swing during treadmill walking after spinal cord injury

Tester, Nicole J.; Howland, Dena R.; Day, Kristin; Suter, Sarah P.; Cantrell, Amy; Behrman, Andrea L.

doi:10.1038/sc.2010.128

Cited by 27 publications

(20 citation statements)

References 21 publications

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“…In conclusion, our findings corroborate the newly emerging observation that adult mammalian spinal cord contains inherent circuits that may be therapeutically recruited and modulated to restore function posttrauma (8,49,53,55). These results collectively suggest it is plausible that direct axonal connections from motor cortex neurons to spinal cord are not essential for reestablishment of basic locomotion after mammalian SCI (55)(56)(57).…”

Section: Discussionsupporting

confidence: 84%

“…Nevertheless, following thoracic lesion of descending motor pathways, neuroplasticity also occurs more caudally in the PSN network and lumbar CPG, a semiautonomous neural circuit for locomotion (45,49). Studies examining "spinalized" cats or humans with incomplete SCI have demonstrated that motor cues, such as weight-suspended treadmill training or treadmill walk, can reanimate the CPG and its reengagement of arm swing, respectively (52,53). Previously, a combinatorial application of direct electrical stimulation or administration of 5-HT receptor agonists enabled locomotion in spinalized rodents with dual spinal cord hemisections by igniting the PSN network for CPG activation through relaying CST signals (44).…”

Section: Discussionmentioning

confidence: 99%

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Defining recovery neurobiology of injured spinal cord by synthetic matrix-assisted hMSC implantation

Ropper

Thakor

Han

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Mesenchymal stromal stem cells (MSCs) isolated from adult tissues offer tangible potential for regenerative medicine, given their feasibility for autologous transplantation. MSC research shows encouraging results in experimental stroke, amyotrophic lateral sclerosis, and neurotrauma models. However, further translational progress has been hampered by poor MSC graft survival, jeopardizing cellular and molecular bases for neural repair in vivo. We have devised an adult human bone marrow MSC (hMSC) delivery formula by investigating molecular events involving hMSCs incorporated in a uniquely designed poly(lactic-co-glycolic) acid scaffold, a clinically safe polymer, following inflammatory exposures in a dorsal root ganglion organotypic coculture system. Also, in rat T9-T10 hemisection spinal cord injury (SCI), we demonstrated that the tailored scaffolding maintained hMSC stemness, engraftment, and led to robust motosensory improvement, neuropathic pain and tissue damage mitigation, and myelin preservation. The scaffolded nontransdifferentiated hMSCs exerted multimodal effects of neurotrophism, angiogenesis, neurogenesis, antiautoimmunity, and antiinflammation. Hindlimb locomotion was restored by reestablished integrity of submidbrain circuits of serotonergic reticulospinal innervation at lumbar levels, the propriospinal projection network, neuromuscular junction, and central pattern generator, providing a platform for investigating molecular events underlying the repair impact of nondifferentiated hMSCs. Our approach enabled investigation of recovery neurobiology components for injured adult mammalian spinal cord that are different from those involved in normal neural function. The uncovered neural circuits and their molecular and cellular targets offer a biological underpinning for development of clinical rehabilitation therapies to treat disabilities and complications of SCI.spinal cord injury | recovery neurobiology | mesenchymal stromal stem cell | PLGA | locomotion R epair of neurotrauma, stroke, and neurodegenerative diseases remains an unmet medical demand because of their pathophysiological complexity and the limited spontaneous healing capacity of adult mammalian CNS. Human mesenchymal stromal stem cells (hMSCs) offer autologous transplantation feasibility (1-4) and have been studied both experimentally and clinically for traumatic brain injury (TBI) and spinal cord injury (SCI) (5-8). Although MSCs possess homeostatic and proneurogenic activities (7, 9), studies relying on neural transdifferentiation (i.e., putative differentiations of MSCs into neural cells without reentering the pluripotency phase) did not show long-term functional improvement in SCI models. The poor outcomes were attributed mainly to suboptimal survival of MSCs, leaving key therapeutic mechanisms undetermined (10). We previously established a 3D cell delivery technology by seeding neural stem cells (NSCs) in biodegradable polymer scaffolds that significantly improved donor efficacy and enabled investigation of NSC repair mechanisms in t...

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Defining recovery neurobiology of injured spinal cord by synthetic matrix-assisted hMSC implantation

Ropper

Thakor

Han

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…To our knowledge, only our group is investigating arm swing during walking post-iSCI. We recently described varied arm swing presentation during walking on a treadmill without assistive devices post-injury [17]. The current study furthers this characterization by describing arm and leg coordination.…”

Section: Introductionsupporting

confidence: 60%

“…Therefore, the 1:1, arm:leg frequency pattern used post-iSCI with slow CWSs may be a compensatory strategy to enhance balance. Experience post-iSCI [17], attributes other than spinal injury (e.g. age, height, weight) known to influence gait [25], and/or the testing environment, however, also should be given equal consideration as factors potentially influencing the results of this study.…”

Section: Discussionmentioning

confidence: 99%

Arm and leg coordination during treadmill walking in individuals with motor incomplete spinal cord injury: A preliminary study

et al. 2012

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Arm and leg coordination naturally emerges during walking, but can be affected by stroke or Parkinson’s disease. The purpose of this preliminary study was to characterize arm and leg coordination during treadmill walking at self-selected comfortable walking speeds (CWSs) in individuals using arm swing with motor incomplete spinal cord injury (iSCI). Hip and shoulder angle cycle durations and amplitudes, strength of peak correlations between contralateral hip and shoulder joint angle time series, the time shifts at which these peak correlations occur, and associated variability were quantified. Outcomes in individuals with iSCI selecting fast CWSs (range, 1.0–1.3 m/s) and speed-matched individuals without neurological injuries are similar. Differences, however, are detected in individuals with iSCI selecting slow CWSs (range, 0.25–0.65 m/s) and may represent compensatory strategies to improve walking balance or forward propulsion. These individuals elicit a 1:1, arm: leg frequency ratio versus the 2:1 ratio observed in non-injured individuals. Shoulder and hip movement patterns, however, are highly reproducible (coordinated) in participants with iSCI, regardless of CWS. This high degree of inter-extremity coordination could reflect an inability to modify a single movement pattern post-iSCI. Combined, these data suggest inter-extremity walking coordination may be altered, but is present after iSCI, and therefore may be regulated, in part, by neural control.

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“…For instance, in human patients with an incomplete spinal cord injury with residual capacity to walk, some of the most visible changes in the locomotor pattern are a reduction in preferred walking speed, an inability to walk at fast speeds, and/or a decreased capacity to sustain walking at fast speeds (Pepin et al 2003a(Pepin et al , 2003b. Spinal cord-injured patients display poor interlimb coordination between the arms and legs, and the majority of patients do not move their arms during walking (Tester et al 2011(Tester et al , 2012. Impairments in interlimb coordination could be due to the slower walking speeds adopted by many spinal cord-injured patients, or the slower walking speeds could impair interlimb coordination.…”

Section: Functional Considerations and Concluding Remarksmentioning

confidence: 99%

Speed-dependent modulation of phase variations on a step-by-step basis and its impact on the consistency of interlimb coordination during quadrupedal locomotion in intact adult cats

Frigon

D’Angelo

Thibaudier

et al. 2014

Journal of Neurophysiology

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Frigon A, D'Angelo G, Thibaudier Y, Hurteau MF, Telonio A, Kuczynski V, Dambreville C. Speed-dependent modulation of phase variations on a step-by-step basis and its impact on the consistency of interlimb coordination during quadrupedal locomotion in intact adult cats. J Neurophysiol 111: 1885-1902, 2014. First published February 12, 2014 doi:10.1152/jn.00524.2013.-It is well established that stance duration changes more than swing duration for a given change in cycle duration. Small variations in cycle duration are also observed at any given speed on a step-by-step basis. To evaluate the step-bystep effect of speed on phase variations, we measured the slopes of the linear regressions between the phases (i.e., stance, swing) and cycle duration during individual episodes at different treadmill speeds in five adult cats. We also determined the pattern of dominance, defined as the phase that varies most with cycle duration. We found a significant effect of speed on hindlimb phase variations, with significant differences observed between the slowest speed of 0.3 m/s compared with faster speeds. Moreover, although patterns of phase dominance were primarily stance/extensor dominated at the slowest speeds, as speed increased the patterns were increasingly categorized as covarying, whereby both stance/extensor and swing/flexor phases changed in approximately equal proportion with cycle duration. Speed significantly affected the relative duration of support periods as well as interlimb phasing between homolateral and diagonal pairs of limbs but not between homologous pairs of limbs. Speed also significantly affected the consistency of interlimb coordination on a step-by-step basis, being less consistent at the slowest speed of 0.3 m/s compared with faster speeds. We found a strong linear relationship between hindlimb phase variations and the consistency of interlimb coordination. Therefore, results show that phase variations on a step-by-step basis are modulated by speed, which appears to influence the consistency of interlimb coordination. locomotion; speed; phase variations; interlimb coordination DURING OVERGROUND OR TREADMILL locomotion, the cycle can be broadly divided into stance and swing phases. Numerous studies have shown that cycle duration is reduced as speed increases, which is accomplished primarily by a reduction in the duration of the stance phase, while the duration of the swing phase is much less affected (reviewed in Frigon 2012;Gossard et al. 2011). This can be demonstrated by plotting the durations of the stance and swing phases as a function of cycle duration and measuring the slopes of the linear regressions (Halbertsma 1983). In most terrestrial walking species, including insects, birds, rodents, reptiles, dogs, cats, macaques, and humans, the slope of the regression between the stance phase and cycle duration (r STA ) is steeper than the slope of the regression between the swing phase and cycle duration (r SW ) (Arshavskii et al.

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Device use, locomotor training and the presence of arm swing during treadmill walking after spinal cord injury

Cited by 27 publications

References 21 publications

Defining recovery neurobiology of injured spinal cord by synthetic matrix-assisted hMSC implantation

Defining recovery neurobiology of injured spinal cord by synthetic matrix-assisted hMSC implantation

Arm and leg coordination during treadmill walking in individuals with motor incomplete spinal cord injury: A preliminary study

Speed-dependent modulation of phase variations on a step-by-step basis and its impact on the consistency of interlimb coordination during quadrupedal locomotion in intact adult cats

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