The Effects of Epidural Stimulation on Individuals with Spinal Cord Injury or Disease and on Animal Models of Spinal Cord Injury: A Systematic Scoping Review

Background As there is no consensus over the efficacy of extracorporeal shockwave therapy in the management of spinal cord injury complications, the current meta-analysis aims to investigate preclinical evidence on the matter. Methods The search strategy was developed based on keywords related to ‘spinal cord injury’ and ‘extracorporeal shockwave therapy’. A primary search was conducted in Medline, Embase, Scopus and Web of Science until the end of 2020. Studies which administered extracorporeal shockwave therapy on spinal cord injury animal models and evaluated motor function and/or histological findings were included. The standardised mean difference with a 95% confidence interval (CI) were calculated. Results Seven articles were included. Locomotion was significantly improved in the extracorporeal shockwave therapy treated group (standardised mean difference 1.68, 95% CI 1.05–2.31, P=0.032). It seems that the efficacy of extracorporeal shockwave therapy with an energy flux density of 0.1 mJ/mm2 is higher than 0.04 mJ/mm2 ( P=0.044). Shockwave therapy was found to increase axonal sprouting (standardised mean difference 1.31, 95% CI 0.65, 1.96), vascular endothelial growth factor tissue levels (standardised mean difference 1.36, 95% CI 0.54, 2.18) and cell survival (standardised mean difference 2.49, 95% CI 0.93, 4.04). It also significantly prevents axonal degeneration (standardised mean difference 2.25, 95% CI 1.47, 3.02). Conclusion Extracorporeal shockwave therapy significantly improves locomotor recovery in spinal cord injury animal models through neural tissue regeneration. Nonetheless, in spite of the promising results and clinical application of extracorporeal shockwave therapy in various conditions, current evidence implies that designing clinical trials on extracorporeal shockwave therapy in the management of spinal cord injury may not be soon. Hence, further preclinical studies with the effort to reach the safest and the most efficient treatment protocol are needed.

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Contusion, dislocation, and distraction: primary hemorrhage and membrane permeability in distinct mechanisms of spinal cord injury

Journal of Neurosurgery Spine ◽

10.3171/spi.2007.6.3.255 ◽

2007 ◽

Vol 6 (3) ◽

pp. 255-266 ◽

Cited By ~ 85

Author(s):

Anthony M. Choo ◽

Jie Liu ◽

Clarrie K. Lam ◽

Marcel Dvorak ◽

Wolfram Tetzlaff ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

White Matter ◽

Animal Models ◽

Membrane Permeability ◽

High Speed ◽

Test System ◽

Fracture Dislocation ◽

Sprague Dawley ◽

Cord Injury

Object In experimental models of spinal cord injury (SCI) researchers have typically focused on contusion and transection injuries. Clinically, however, other injury mechanisms such as fracture–dislocation and distraction also frequently occur. The objective of the present study was to compare the primary damage in three clinically relevant animal models of SCI. Methods Contusion, fracture–dislocation, and flexion–distraction animal models of SCI were developed. To visualize traumatic increases in cellular membrane permeability, fluorescein–dextran was infused into the cerebrospi-nal fluid prior to injury. High-speed injuries (approaching 100 cm/second) were produced in the cervical spine of deeply anesthetized Sprague–Dawley rats (28 SCI and eight sham treated) with a novel multimechanism SCI test system. The animals were killed immediately thereafter so that the authors could characterize the primary injury in the gray and white matter. Sections stained with H & E showed that contusion and dislocation injuries resulted in similar central damage to the gray matter vasculature whereas no overt hemorrhage was detected following distraction. Contusion resulted in membrane disruption of neuronal somata and axons localized within 1 mm of the lesion epicenter. In contrast, membrane compromise in the dislocation and distraction models was observed to extend rostrally up to 5 mm, particularly in the ventral and lateral white matter tracts. Conclusions Given the pivotal nature of hemorrhagic necrosis and plasma membrane compromise in the initiation of downstream SCI pathomechanisms, the aforementioned differences suggest the presence of mechanism-specific injury regions, which may alter future clinical treatment paradigms.

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The current state of knowledge on digital rectal stimulation in traumatic and non-traumatic spinal cord injury: A scoping review

Archives of Physical Medicine and Rehabilitation ◽

10.1016/j.apmr.2020.12.023 ◽

2021 ◽

Author(s):

Joanne Wincentak ◽

Ying Xu ◽

Louise Rudden ◽

Dilshad Kassam-Lallani ◽

Amy Mullin ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Scoping Review ◽

Traumatic Spinal Cord Injury ◽

Current State ◽

Cord Injury

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Systematic Evaluation of Spinal Cord Injury Animal Models in the Field of Biomaterials

Tissue Engineering Part B Reviews ◽

10.1089/ten.teb.2021.0194 ◽

2021 ◽

Author(s):

Kest Verstappen ◽

René Aquarius ◽

Alexey Klymov ◽

Kimberley E. Wever ◽

Lyan Damveld ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Animal Models ◽

Systematic Evaluation ◽

Cord Injury

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Factors Which Facilitate or Impede Interpersonal Interactions and Relationships after Spinal Cord Injury: A Scoping Review with Suggestions for Rehabilitation

Rehabilitation Research and Practice ◽

10.1155/2016/9373786 ◽

2016 ◽

Vol 2016 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Delena Amsters ◽

Sarita Schuurs ◽

Kiley Pershouse ◽

Bettina Power ◽

Yvonne Harestad ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Scoping Review ◽

English Language ◽

International Classification Of Functioning ◽

Interpersonal Interactions ◽

Self Image ◽

Language Studies ◽

Cord Injury ◽

Review Question

Interpersonal interactions and relationships can influence an individual’s perceptions of health and quality of life in the presence of disability. In the case of people with spinal cord injury (SCI), positive interpersonal interactions and relationships have been shown to contribute to resilience and adaptability. Understanding factors which facilitate or impede the development and maintenance of relationships after SCI may form the basis for proactive relationship support for people with SCI. To gain a broad insight into these factors, a scoping review was undertaken. Databases were searched for English language studies published between 2000 and 2015 that informed the review question. Sixty-two (62) studies were identified. Thematic analysis was conducted on data extracted from the studies and 51 factors which may facilitate relationships and 38 factors which may impede relationships after SCI were noted. The majority of factors could be categorized as environmental or personal according to the domains of the International Classification of Functioning, Disability, and Health (ICF). The facilitating factors included partner and social support, reciprocity in relationships, and presenting oneself positively. Impeding factors included physical environmental barriers, real and perceived social biases, and poor self-image. Factors identified may inform the provision of supportive, holistic rehabilitation for people with SCI.

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Improving outcome of sensorimotor functions after traumatic spinal cord injury

F1000Research ◽

10.12688/f1000research.8129.1 ◽

2016 ◽

Vol 5 ◽

pp. 1018 ◽

Cited By ~ 2

Author(s):

Volker Dietz

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Animal Models ◽

Technical Assistance ◽

Cord Injury ◽

Descending Input ◽

Muscle Activations ◽

Clinical Conditions ◽

Functional Movements ◽

Experimental Stage

In the rehabilitation of a patient suffering a spinal cord injury (SCI), the exploitation of neuroplasticity is well established. It can be facilitated through the training of functional movements with technical assistance as needed and can improve outcome after an SCI. The success of such training in individuals with incomplete SCI critically depends on the presence of physiological proprioceptive input to the spinal cord leading to meaningful muscle activations during movement performances. Some actual preclinical approaches to restore function by compensating for the loss of descending input to spinal networks following complete/incomplete SCI are critically discussed in this report. Electrical and pharmacological stimulation of spinal neural networks is still in the experimental stage, and despite promising repair studies in animal models, translations to humans up to now have not been convincing. It is possible that a combination of techniques targeting the promotion of axonal regeneration is necessary to advance the restoration of function. In the future, refinement of animal models according to clinical conditions and requirements may contribute to greater translational success.

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The Hemisection Approach in Large Animal Models of Spinal Cord Injury: Overview of Methods and Applications

Journal of Investigative Surgery ◽

10.1080/08941939.2018.1492048 ◽

2018 ◽

Vol 33 (3) ◽

pp. 240-251

Author(s):

S. Wilson ◽

S. J. Nagel ◽

L. A. Frizon ◽

D. C. Fredericks ◽

N. A. DeVries-Watson ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Animal Models ◽

Large Animal ◽

Large Animal Models ◽

Cord Injury

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High-frequency epidural stimulation across the respiratory cycle evokes phrenic short-term potentiation after incomplete cervical spinal cord injury

Journal of Neurophysiology ◽

10.1152/jn.00913.2016 ◽

2017 ◽

Vol 118 (4) ◽

pp. 2344-2357 ◽

Cited By ~ 7

Author(s):

Elisa J. Gonzalez-Rothi ◽

Kristi A. Streeter ◽

Marie H. Hanna ◽

Anna C. Stamas ◽

Paul J. Reier ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

High Frequency ◽

Muscle Activation ◽

Cervical Spinal Cord ◽

Cervical Spinal Cord Injury ◽

Burst Frequency ◽

Epidural Stimulation ◽

Term Potentiation ◽

Cord Injury

C2 spinal hemilesion (C2Hx) paralyzes the ipsilateral diaphragm, but recovery is possible through activation of “crossed spinal” synaptic inputs to ipsilateral phrenic motoneurons. We tested the hypothesis that high-frequency epidural stimulation (HF-ES) would potentiate ipsilateral phrenic output after subacute and chronic C2Hx. HF-ES (300 Hz) was applied to the ventrolateral C4 or T2 spinal cord ipsilateral to C2Hx in anesthetized and mechanically ventilated adult rats. Stimulus duration was 60 s, and currents ranged from 100 to 1,000 µA. Bilateral phrenic nerve activity and ipsilateral hypoglossal (XII) nerve activity were recorded before and after HF-ES. Higher T2 stimulus currents potentiated ipsilateral phasic inspiratory activity at both 2 and 12 wk post-C2Hx, whereas higher stimulus currents delivered at C4 potentiated ipsilateral phasic phrenic activity only at 12 wk ( P = 0.028). Meanwhile, tonic output in the ipsilateral phrenic nerve reached 500% of baseline values at the high currents with no difference between 2 and 12 wk. HF-ES did not trigger inspiratory burst-frequency changes. Similar responses occurred following T2 HF-ES. Increases in contralateral phrenic and XII nerve output were induced by C4 and T2 HF-ES at higher currents, but the relative magnitude of these changes was small compared with the ipsilateral phrenic response. We conclude that following incomplete cervical spinal cord injury, HF-ES of the ventrolateral midcervical or thoracic spinal cord can potentiate efferent phrenic motor output with little impact on inspiratory burst frequency. However, the substantial increases in tonic output indicate that the uninterrupted 60-s stimulation paradigm used is unlikely to be useful for respiratory muscle activation after spinal injury. NEW & NOTEWORTHY Previous studies reported that high-frequency epidural stimulation (HF-ES) activates the diaphragm following acute spinal transection. This study examined HF-ES and phrenic motor output following subacute and chronic incomplete cervical spinal cord injury. Short-term potentiation of phrenic bursting following HF-ES illustrates the potential for spinal stimulation to induce respiratory neuroplasticity. Increased tonic phrenic output indicates that alternatives to the continuous stimulation paradigm used in this study will be required for respiratory muscle activation after spinal cord injury.

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