Induced Neural Activity Promotes an Oligodendroglia Regenerative Response in the Injured Spinal Cord and Improves Motor Function after Spinal Cord Injury

Abstract BackgroundTo investigate the effect of mmu-miR-27a-5p on macrophage polarization in the injured spinal cord and the recovery of motor function after spinal cord injury (SCI) in mice.MethodsA total of 160 specific-pathogen-free male mice were randomly divided into sham, model, mmu-miR-27a-5p, mmu-miR-27a-5p-negative control (NC) groups, with 40 mice in each group. Hindlimb motor function was assessed using the Basso Mouse scale (BMS) before injury and at 1, 3, 7, and 14 days after surgery. Spinal cord tissue samples were obtained at 1, 3, 7, and 14 days after surgery, and macrophage polarization types were detected by using western blot analysis, immunofluorescence, flow cytometry and RT-qPCR.ResultsThe BMS score in the mmu-miR-27a-5p group was significantly higher than that in the model and mmu-miR-27a-5p-NC groups at 7 and 14 days after SCI (X2=26.45-57.62, P<0.05). No significant changes in the expression of M1 markers IL-1β, TNF-α and M2 markers IL-10, Arginase-1 at each time point in the sham group (P=0.96). The expression of IL-1β and TNF-α was significantly lower, while the expression of IL-10 and Arginase-1 were significantly higher in the mmu-miR-27a-5p group as compared to the model and mmu-miR-27a-5p-NC groups at 7 and 14 days after SCI (P<0.05).ConclusionAdministration of mmu-miR-27a-5p can promote the polarization of macrophages to the M2 phenotype in the injured spinal cord, and improve motor function recovery within 14 days after SCI in mice.

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Therapeutic Stimulation for Restoration of Function After Spinal Cord Injury

Physiology ◽

10.1152/physiol.00010.2017 ◽

2017 ◽

Vol 32 (5) ◽

pp. 391-398 ◽

Cited By ~ 14

Author(s):

Aiva Ievins ◽

Chet T. Moritz

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Motor Function ◽

Injured Spinal Cord ◽

Autonomic Functions ◽

Bladder Control ◽

Cellular Environment ◽

Cord Injury ◽

Incurable Condition ◽

Stimulation Of

Paralysis due to spinal cord injury can severely limit motor function and independence. This review summarizes different approaches to electrical stimulation of the spinal cord designed to restore motor function, with a brief discussion of their origins and the current understanding of their mechanisms of action. Spinal stimulation leads to impressive improvements in motor function along with some benefits to autonomic functions such as bladder control. Nonetheless, the precise mechanisms underlying these improvements and the optimal spinal stimulation approaches for restoration of motor function are largely unknown. Finally, spinal stimulation may augment other therapies that address the molecular and cellular environment of the injured spinal cord. The fact that several stimulation approaches are now leading to substantial and durable improvements in function following spinal cord injury provides a new perspectives on the previously “incurable” condition of paralysis.

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Assessment of neuroprotective role of PPAR-gamma agonist in spinal cord injury as possible therapeutic agents

Journal of Experimental and Applied Animal Sciences ◽

10.20454/jeaas.2018.1387 ◽

2018 ◽

Vol 2 (3) ◽

pp. 251-259

Author(s):

Zahra Jahanbakhsh ◽

Hassan Ghoshooni ◽

Mohammad Taghi Mohammadi

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Oxidative Damage ◽

Motor Function ◽

Ppar Gamma ◽

Control Group ◽

Injured Spinal Cord ◽

Histopathological Changes ◽

Cord Injury ◽

Ppar Gamma Agonist

It has been reported that peroxisome proliferator-activated receptor (PPAR)-gamma agonist, pioglitazone, has several beneficial roles in many pathological states of nervous tissues. Then in the present study, we aimed to examine the neuroprotective actions of pioglitazone (PPAR-gamma agonist) on motor function, histopathological changes and oxidative damage during spinal cord injury (SCI) in rats. Twenty-four male Wistar rats were randomly divided into three groups as follows; sham, control injury and pioglitazone-treated injured groups. SCI was performed according to the Ping-Weight Drop (contusion) model in rat. The animals received pioglitazone (3 mg/kg) intraperitoneally at times of 15 min after injury and then each 12 hours for seven days. At day seven after SCI, the malondialdehyde and glutathione levels were assessed using biochemical techniques. Histopathological alterations in injured spinal cord and motor function recovery were also assessed after six weeks. Induction of SCI in control group significantly increased the malondialdehyde levels (56%, P=0.002) and decreased the content of glutathione (39±4 nMol/mL) compared to control group (49±6 nMol/mL). Pioglitazone in treated injured rats significantly decreased the malondialdehyde levels (37%, P=0.018) but not glutathione levels (42±1 nMol/mL) compared to sham group. In addition, pioglitazone noticeably improved the histopathological changes of injured spinal cord but not motor function. Our findings revealed that pioglitazone decreases histopathological changes and oxidative damage of injured spinal cord. However, it is suggested that pioglitazone must be applied at higher doses for improving motor function during 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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