The Relationship between Trans-Lesional Conduction, Motor Neuron Pool Excitability, and Motor Function in Dogs with Incomplete Recovery from Severe Spinal Cord Injury

Spinal cord epidural stimulation (scES) combined with activity-based training can promote motor function recovery in individuals with motor complete spinal cord injury (SCI). The characteristics of motor neuron recruitment, which influence different aspects of motor control, are still unknown when motor function is promoted by scES. Here, we enrolled five individuals with chronic motor complete SCI implanted with a scES unit to study the recruitment order of motor neurons during standing enabled by scES. We recorded high-density electromyography (HD-EMG) signals on the vastus lateralis muscle, and inferred the order of recruitment of motor neurons from the relation between amplitude and conduction velocity of the scES-evoked EMG responses along the muscle fibers. Conduction velocity of scES-evoked responses was modulated over time, while stimulation parameters and standing condition remained constant, with average values ranging between 3.0±0.1 and 4.4±0.3 m/s. We found that the human spinal circuitry receiving epidural stimulation can promote both orderly (according to motor neuron size) and inverse trends of motor neuron recruitment, and that the engagement of spinal networks promoting rhythmic activity may favor orderly recruitment trends. Conversely, the different recruitment trends did not appear to be related with time since injury or scES implant, nor to the ability to achieve independent knees extension, nor to the conduction velocity values. The proposed approach can be implemented to investigate the effects of stimulation parameters and training-induced neural plasticity on the characteristics of motor neuron recruitment order, contributing to improve mechanistic understanding and effectiveness of epidural stimulation-promoted motor recovery after SCI.

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Adenovirus-mediated FGF-2 gene promotes motor function of rats with spinal cord injury

Academic Journal of Second Military Medical University ◽

10.3724/sp.j.1008.2011.01150 ◽

2011 ◽

Vol 31 (10) ◽

pp. 1150-1152

Author(s):

Yan-ling YANG

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Motor Function ◽

Cord Injury

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Transplantation of Human iPS Cell-Derived Neural Cells with an Artificial Nerve Conduit Leads to Cellular Retention in the Transplanted Area and Improves Motor Function in a Mouse Spinal Cord Injury Model

Journal of St Marianna University ◽

10.17264/stmarieng.10.27 ◽

2019 ◽

Vol 10 (2) ◽

pp. 27-37

Author(s):

Ken Tomochika ◽

Nagisa Arimitsu ◽

Masanori A. Murayama ◽

Chieko Hirotsu ◽

Kazufumi Nagata ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Motor Function ◽

Nerve Conduit ◽

Neural Cells ◽

Ips Cell ◽

Mouse Spinal Cord ◽

Spinal Cord Injury Model ◽

Injury Model ◽

Cord Injury

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Bone marrow mesenchymal stem cells-derived exosomes reduce apoptosis and inflammatory response during spinal cord injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway

Human & Experimental Toxicology ◽

10.1177/09603271211003311 ◽

2021 ◽

pp. 096032712110033

Author(s):

Liying Fan ◽

Jun Dong ◽

Xijing He ◽

Chun Zhang ◽

Ting Zhang

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Bone Marrow ◽

Spinal Cord Injury ◽

Mesenchymal Stem Cells ◽

Motor Function ◽

Inflammatory Factors ◽

Cord Injury ◽

Marrow Mesenchymal Stem Cells ◽

Apoptosis And Inflammation

Spinal cord injury (SCI) is one of the most common destructive injuries, which may lead to permanent neurological dysfunction. Currently, transplantation of bone marrow mesenchymal stem cells (BMSCs) in experimental models of SCI shows promise as effective therapies. BMSCs secrete various factors that can regulate the microenvironment, which is called paracrine effect. Among these paracrine substances, exosomes are considered to be the most valuable therapeutic factors. Our study found that BMSCs-derived exosomes therapy attenuated cell apoptosis and inflammation response in the injured spinal cord tissues. In in vitro studies, BMSCs-derived exosomes significantly inhibited lipopolysaccharide (LPS)-induced PC12 cell apoptosis, reduced the secretion of pro-inflammatory factors including tumor necrosis factor (TNF)-α and IL (interleukin)-1β and promoted the secretion of anti-inflammatory factors including IL-10 and IL-4. Moreover, we found that LPS-induced protein expression of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear transcription factor-κB (NF-κB) was significantly downregulated after treatment with BMSCs-derived exosomes. In in vivo studies, we found that hindlimb motor function was significantly improved in SCI rats with systemic administration of BMSCs-derived exosomes. We also observed that the expression of pro-apoptotic proteins and pro-inflammatory factors was significantly decreased, while the expression of anti-apoptotic proteins and anti-inflammatory factors were upregulated in SCI rats after exosome treatment. In conclusion, BMSCs-derived exosomes can inhibit apoptosis and inflammation response induced by injury and promote motor function recovery by inhibiting the TLR4/MyD88/NF-κB signaling pathway, which suggests that BMSCs-derived exosomes are expected to become a new therapeutic strategy for SCI.

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