Spinal Cord
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2021 ◽  
Amandine Robac ◽  
Pauline Neveu ◽  
Alizée Hugede ◽  
Elisabeth Garrido ◽  
Lionel Nicol ◽  

Abstract Spinal cord injury (SCI) is an incurable condition in which the brain is disconnected partially or completely from the periphery. Mainly SCI are traumatic and are due to traffic, domestic or sport accidents. To date SCI are incurable and let, most of the time, the patients with a permanent loss of sensitive and motor functions. Therefore, since several decades researchers tried to develop treatments to cure SCI. Among them, recently, our lab have demonstrated that in mice, repetitive trans-spinal magnetic stimulation (rTSMS) can, after SCI, modulate the lesion scar and can induce functional locomotor recovery non-invasively. These results are promising, however before to translate them to Humans it is important to reproduce them in a more clinically relevant model. Indeed, SCI do not lead to the same cellular events in mice and Humans. In particular, SCI in Humans induce the formation of cystic cavities. That is why we propose here to validate the effects of rTSMS in rat, animal model in which SCI lead to the formation of cystic cavities, after penetrating and contusive SCI. To do so, several techniques including immunohistochemical, behavioral and MRI have been performed. Our results demonstrate that rTSMS, in both SCI models, modulates the lesion scar by decreasing the formation of cystic cavities and by improving axonal survival. Moreover, rTSMS, in both models, enhances functional locomotor recovery. Altogether, our study describes that rTSMS exerts positive effects after SCI in rats. This study is a further step towards the use of this treatment in Humans.

Johannie Audet ◽  
Charly G. Lecomte

Tonic or phasic electrical epidural stimulation of the lumbosacral region of the spinal cord facilitates locomotion and standing in a variety of preclinical models with severe spinal cord injury. However, the mechanisms of epidural electrical stimulation that facilitate sensorimotor functions remain largely unknown. This review aims to address how epidural electrical stimulation interacts with spinal sensorimotor circuits and discusses the limitations that currently restrict the clinical implementation of this promising therapeutic approach.

2021 ◽  
Vol 15 ◽  
Amrei Zieriacks ◽  
Mirko Aach ◽  
Alexis Brinkemper ◽  
Daniela Koller ◽  
Thomas Armin Schildhauer ◽  

This study aimed to assess the outcome of acute and chronic participants with spinal cord injury (SCI) after 12 weeks of bodyweight supported treadmill training (BWSTT) with a hybrid assistive limb exoskeleton (HAL). Acute participants were defined as ≤12 months between SCI and training, chronic participants >12 months between SCI and training. We assessed whether HAL-assisted BWSTT is advantageous for acute and chronic participants and if length of time post injury impacts the outcome of HAL-assisted BWSTT. As the primary outcome, we assessed the time needed for the 10 meter walk test (10MWT). Hundred and twenty-one individuals participated in a 12-week HAL-assisted BWSTT five times a week. We regularly conducted a 10MWT, a 6 minute walk test (6MWT), and assessed the walking index for spinal cord injury (WISCI II) and lower extremity motor score (LEMS) to evaluate the gait performance without the exoskeleton. Distance and time were recorded by the treadmill while the participant was walking with the exoskeleton. All participants benefit from the 12-week HAL-assisted BWSTT. A significant difference between acute and chronic participants' outcomes was found in 6MWT, LEMS, and WISCI II, though not in 10MWT. Although chronic participants improved significantly lesser than acute participants, they did improve their outcome significantly compared to the beginning. Hybrid assistive limb-assisted BWSTT in the rehabilitation of patients with SCI is advantageous for both acute and chronic patients. We could not define a time related cut-off threshold following SCI for effectiveness of HAL-assisted BWSTT.

2021 ◽  
Vol 31 ◽  
pp. 33-40
Dayu Pan ◽  
Weixiao Liu ◽  
Shibo Zhu ◽  
Baoyou Fan ◽  
Nanxi Yu ◽  

2021 ◽  
Vol 0 (0) ◽  
Lirong Zhang ◽  
Keyue Ruan ◽  
Guoju Sang ◽  
Zhaoyang Xu ◽  
Wu Tong ◽  

Abstract Introduction The pseudorabies virus (PRV) gene encoding thymidine kinase (tk) is an important virulence-associated factor. Attenuation of PRV in susceptible animals is a frequent result of tk deletion. The aim of the study was to assess the pathogenicity of tk-deleted PRV in rats. Material and Methods Sprague Dawley rats were infected with the tk-deleted PRV strain SuHV-1 ΔTK:247via intranasal or intramuscular inoculation. PRV loads in ten tissues from dead and euthanised rats were determined using real-time PCR. Results Infection with SuHV-1 ΔTK:247 could cause death in rats. The 50% lethal dose (LD50) of SuHV-1 ΔTK:247 via intranasal inoculation was 103.16 TCID50 in rats. Intramuscular inoculation required a higher dose of SuHV-1 ΔTK:247 (105.0 TCID50). A high SuHV-1 ΔTK:247 titre was observed in the trigeminal ganglia or spinal cord of dead rats. Conclusion The results of this study show that rats are highly susceptible to PRV infection, and tk deletion did not completely diminish the pathogenicity of PRV in rats.

2021 ◽  
Craig T Jacobs ◽  
Aarti Kejriwal ◽  
Katrinka M Kocha ◽  
Kevin Y Jin ◽  
Peng Huang

During neural development, progenitor cells generate different types of neurons in specific time windows. Despite the characterisation of many of the transcription factor networks involved in these differentiation events, the mechanism behind their temporal regulation is poorly understood. To address this question, we studied the temporal differentiation of the simple lateral floor plate (LFP) domain in the zebrafish spinal cord. LFP progenitors sequentially generate early-born Kolmer-Agduhr″ (KA″) interneurons and late-born V3 interneurons. Analysis using a Notch signalling reporter demonstrates that these cell populations have distinct Notch signalling profiles. Not only do V3 cells receive higher total levels of Notch response, but they collect this response over a longer duration compared to V3 cells. To test whether the duration of Notch signalling determines the temporal cell fate specification, we combined a transgene that constitutively activates Notch signalling in the ventral spinal cord with a heat shock inducible Notch signalling terminator to switch off Notch response at any given time. Sustained Notch signalling results in expanded LFP progenitors while KA″ and V3 interneurons fail to specify. Early termination of Notch signalling leads to exclusively KA″ cell fate, despite the high level of Notch signalling, whereas late attenuation of Notch signalling drives only V3 cell fate. This suggests that the duration of Notch signalling is instructive in cell fate specification. Interestingly, knockdown experiments reveal a role for the Notch ligand Jag2b in maintaining LFP progenitors and limiting their differentiation into KA″ and V3 cells. Our results indicate that Notch signalling is required for neural progenitor maintenance while a specific attenuation timetable defines the fate of the postmitotic progeny.

2021 ◽  
Vol 2 ◽  
Kendra R. Todd ◽  
Jan W. Van Der Scheer ◽  
Jeremy J. Walsh ◽  
Garett S. Jackson ◽  
Gabriel U. Dix ◽  

Introduction: Persons with spinal cord injury (SCI) often report high levels of neuropathic pain (NP) and poor well-being, which may result from increased inflammation. This study examined the impact of sub-maximal aerobic exercise on NP, inflammation and psychological affect among adults with SCI.Methods: Eight active adults with tetraplegia (n-4, AIS A-C) and paraplegia (n = 4, AIS A-C) performed 30-min of arm-crank aerobic exercise and reported their ratings of perceived exertion (RPE) each minute. Measures of NP, affect, and inflammatory cytokines (IL-6, IL-10, IL-1ra, TNF-α) were taken pre-(T0), immediately post-(T1), and 90-min post-exercise (T2).Results: NP decreased between T0 and T1 for tetraplegics (−60%, d = 0.47; CI = −0.32, 2.02) and paraplegics (−16%, d = 0.15; CI = −0.30, 0.90). Correlations between change in cytokines and change in NP were medium-to large for tetraplegics (rs ranged from −0.820 to 0.965) and paraplegics (rs ranged from −0.598 to 0.833). However, the pattern of correlations between change in cytokines and affect was inconsistent between groups. Lower baseline levels of IL-1ra predicted greater decreases in NP immediately post-exercise (r = 0.83, p = 0.01).Conclusion: Sub-maximal exercise can positively impact NP for some persons with SCI. Further experimental research should identify the optimal exercise intensity to reduce NP for persons with SCI, in addition to understanding biomarkers which may predict changes in NP.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT03955523.

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