The Translesional Spinal Network and Its Reorganization after Spinal Cord Injury

Krůpa, Petr; Siddiqui, Ahad M.; Grahn, Peter J.; Islam, Riazul; Chen, Bingkun K.; Madigan, Nicolas N.; Windebank, Anthony J.; Lavrov, Igor

doi:10.1177/1073858420966276

Cited by 18 publications

(16 citation statements)

References 164 publications

(211 reference statements)

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“…Meanwhile, the supralesional EES at C5 did not affect locomotion in the front legs due to supraspinal control. In this study, electrodes were implanted two weeks before SCI at Th9 following the same protocol but with changing the supralesional stimulation site from C5 to Th5 segment with the idea that EES located closer to the injury may facilitate the newly growing axons through the injury, thereby facilitating the formation of a translesional network and promoting interactions between neural networks above and below the injury [ 35 ]. Animals were implanted with stimulating and reference Teflon-coated wire electrodes (AS632, Cooner Wire Company, Chatsworth, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation

Islamov

Bashirov

Izmailov

et al. 2022

Cells

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The contemporary strategy for spinal cord injury (SCI) therapy aims to combine multiple approaches to control pathogenic mechanisms of neurodegeneration and stimulate neuroregeneration. In this study, a novel regenerative approach using an autologous leucoconcentrate enriched with transgenes encoding vascular endothelial growth factor (VEGF), glial cell line-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) combined with supra- and sub-lesional epidural electrical stimulation (EES) was tested on mini-pigs similar in morpho-physiological scale to humans. The complex analysis of the spinal cord recovery after a moderate contusion injury in treated mini-pigs compared to control animals revealed: better performance in behavioural and joint kinematics, restoration of electromyography characteristics, and improvement in selected immunohistology features related to cell survivability, synaptic protein expression, and glial reorganization above and below the injury. These results for the first time demonstrate the positive effect of intravenous infusion of autologous genetically-enriched leucoconcentrate producing recombinant molecules stimulating neuroregeneration combined with neuromodulation by translesional multisite EES on the restoration of the post-traumatic spinal cord in mini-pigs and suggest the high translational potential of this novel regenerative therapy for SCI patients.

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Section: Methodsmentioning

confidence: 99%

New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation

Islamov

Bashirov

Izmailov

et al. 2022

Cells

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“…According to the American Spinal Injury Association, most patients with complete SCI retain some undamaged descending connections, but their spinal cord excitability is severely disrupted, resulting in the loss of function of the intact spinal circuits below the injury (Rossignol and Frigon, 2011 ; Marder et al, 2014 ; Eisdorfer et al, 2020 ). Evidence suggests that neuromodulation technologies can activate the development of sublesional spinal networks, which are isolated from supraspinal commands after SCI, by reestablishing the levels of excitability, and enabling descending motor signals via residual connections (Krupa et al, 2020 ). Whereas the propriospinal networks and the descending reticulospinal commands are putatively the greatest contributors to recovery from anatomically incomplete lesions, recovery from complete lesions is likely due to local lumbar circuit plasticity driven by afferent input (Eisdorfer et al, 2020 ) (see Figure 2A ).…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

“…There is evidence that sublesional and supralesional spinal circuits can form a translesional spinal network after SCI (Krupa et al, 2020 ). The existence of this translesional spinal network is one potential mechanism by which electrical stimulation neuromodulation promotes sensorimotor recovery.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

“…The existence of this translesional spinal network is one potential mechanism by which electrical stimulation neuromodulation promotes sensorimotor recovery. Evidence largely derived from rodent models of contusion or staggered hemisection suggests that locomotor function depends on relays of spinal INs and connections via newly sprouted axons between spared long tracts and propriospinal circuits (May et al, 2017 ; Krupa et al, 2020 ). Although substantial progress has been made in understanding the mechanisms underpinning some forms of neuromodulation, much remains to be established.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

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Restoring Sensorimotor Function Through Neuromodulation After Spinal Cord Injury: Progress and Remaining Challenges

et al. 2021

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Spinal cord injury (SCI) is a major disability that results in motor and sensory impairment and extensive complications for the affected individuals which not only affect the quality of life of the patients but also result in a heavy burden for their families and the health care system. Although there are few clinically effective treatments for SCI, research over the past few decades has resulted in several novel treatment strategies which are related to neuromodulation. Neuromodulation—the use of neuromodulators, electrical stimulation or optogenetics to modulate neuronal activity—can substantially promote the recovery of sensorimotor function after SCI. Recent studies have shown that neuromodulation, in combination with other technologies, can allow paralyzed patients to carry out intentional, controlled movement, and promote sensory recovery. Although such treatments hold promise for completely overcoming SCI, the mechanisms by which neuromodulation has this effect have been difficult to determine. Here we review recent progress relative to electrical neuromodulation and optogenetics neuromodulation. We also examine potential mechanisms by which these methods may restore sensorimotor function. We then highlight the strengths of these approaches and remaining challenges with respect to its application.

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“…Preclinical research focused on the various types of SCI has confirmed the promising, beneficial effects of immunomodulatory therapy [2][3][4][5][6], stem cells [7][8][9][10][11], trophic factors [12][13][14][15][16], electric stimulation [17][18][19], axonal regeneration and plasticity; all with the potential to enable an improved functional outcome. In the laboratory setting, several models of SCI are used.…”

Section: Introductionmentioning

confidence: 98%

New Model of Ventral Spinal Cord Lesion Induced by Balloon Compression in Rats

et al. 2020

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Despite the variety of experimental models of spinal cord injury (SCI) currently used, the model of the ventral compression cord injury, which is commonly seen in humans, is very limited. Ventral balloon compression injury reflects the common anatomical mechanism of a human lesion and has the advantage of grading the injury severity by controlling the inflated volume of the balloon. In this study, ventral compression of the SCI was performed by the anterior epidural placement of the balloon of a 2F Fogarty’s catheter, via laminectomy, at the level of T10. The balloon was rapidly inflated with 10 or 15 μL of saline and rested in situ for 5 min. The severity of the lesion was assessed by behavioral and immunohistochemical tests. Compression with the volume of 15 μL resulted in severe motor and sensory deficits represented by the complete inability to move across a horizontal ladder, a final Basso, Beattie and Bresnahan (BBB) score of 7.4 and a decreased withdrawal time in the plantar test (11.6 s). Histology and immunohistochemistry revealed a significant loss of white and gray matter with a loss of motoneuron, and an increased size of astrogliosis. An inflation volume of 10 μL resulted in a mild transient deficit. There are no other balloon compression models of ventral spinal cord injury. This study provided and validated a novel, easily replicable model of the ventral compression SCI, introduced by an inflated balloon of Fogarty´s catheter. For a severe incomplete deficit, an inflated volume should be maintained at 15 μL.

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The Translesional Spinal Network and Its Reorganization after Spinal Cord Injury

Cited by 18 publications

References 164 publications

New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation

New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation

Restoring Sensorimotor Function Through Neuromodulation After Spinal Cord Injury: Progress and Remaining Challenges

New Model of Ventral Spinal Cord Lesion Induced by Balloon Compression in Rats

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