scholarly journals Ultrashort Wave Combined with Human Umbilical Cord Mesenchymal Stem Cell (HUC-MSC) Transplantation Inhibits NLRP3 Inflammasome and Improves Spinal Cord Injury via MK2/TTP Signalling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Li Na ◽  
Shuai Wang ◽  
Tongtong Liu ◽  
Lixin Zhang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Combination Therapy ◽  
Nlrp3 Inflammasome ◽  
Signalling Pathway ◽  
Regulatory Mechanisms ◽  
Inflammatory Factors ◽  
Expression Levels ◽  
Cord Injury ◽  
Nlrp3 Expression

Objective. To investigate the curative effects of HUC-MSCs combined with USW on spinal cord injury (SCI) and the effects on inflammatory microenvironment and to explore the regulatory mechanisms of MK2/TTP signalling pathway and NLRP3 inflammasome. Methods. The SCI rat model was established using the modified Allen method; rats were administered with USW, HUC-MSCs, and combination therapy of USW and HUC-MSCs; the therapeutic efficacies in each group of rats were monitored and represented in BBB score. SCI levels were observed using HE staining and IF. The microglia polarisation state and released contents of inflammatory factors were detected. IF and Western Blotting were performed on to detect the expression levels of MK2/TTP signalling pathway and NLRP3 inflammasome-related proteins. Furthermore, the regulatory mechanisms of MK2/TTP pathway and NLRP3 were explored by performing on the in vitro study. Results. Combination therapy of USW and HUC-MSCs was found of significant efficacy on improving motor functions of SCI rats, and it was further proved that this combination therapy can reduce spinal cord injury in SCI rats, of which USW plays a more important role. While transplantation of HUC-MSCs can promote microglial cells developing to SCI repair, and M2 microglial cells were taking advantages gradually. The combination therapy can inhibit the expression of MK2; downregulate NLRP3 inflammasome; suppress the expression levels of pro-caspase-1, pro-IL-1β, and pro-IL-18; and simultaneously suppress the release of IL-1β and IL-18, thereby reducing spinal cord neurons apoptosis. It was found that the steady state of microglial polarisation maintained by combined treatment of USW and HUC-MSCs was destroyed with the upregulation of MK2 expression in cells, of which, M1 type microglial cell was dominant and the increased contents of inflammatory factors were detected. However, overexpressed MK2 relieved the inhibition of NLRP3 expression by TTP. Conclusions. Combination therapy of USW and HUC-MSCs can downregulate NLRP3 expression, relieve inflammatory responses, improve immune microenvironment, and rescue spinal cord injury via suppressing phosphorylation level of MK2.

scholarly journals EZH2 Mediates miR-146a-5p/HIF-1α to Alleviate Inflammation and Glycolysis after Acute Spinal Cord Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Shuangfei Ni ◽  
Bo Yang ◽  
Lei Xia ◽  
Huafeng Zhang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cerebrospinal Fluid ◽  
Underlying Mechanism ◽  
Acute Spinal Cord Injury ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Expression Levels ◽  
Tnf Α ◽  
Cord Injury

Acute spinal cord injury (ASCI) is a severe traumatic disease of the central nervous system, the underlying mechanism of which is unclear. This study was intended to study the role of EZH2 and miR-146a-5p/HIF-1α in inflammation and glycolysis after ASCI, providing reference and basis for the clinical treatment and prognosis of ASCI injury. We used lipopolysaccharide (LPS) to induce inflammation of microglia, and we constructed the ASCI animal model. qRT-PCR detected the relative expression levels of EZH2, HIF-1α, miR-146a-5p, IL-6, TNF-α, IL-17, PKM2, GLUT1, and HK2 in cells and tissues. Western blot was performed to detect the expression levels of EZH2, HIF-1α, H3K27me3, IL-6, TNF-α, IL-17, PKM2, GLUT1, and HK2. ChIP verified the enrichment of H3K27me3 in the miR-146a-5p promoter region. Bioinformatics predicted the binding sites of HIF-1α and miR-146a-5p, and dual-luciferase reporter assay verified the binding of HIF-1α and miR-146a-5p. ELISA detects the levels of inflammatory factors IL-6, TNF-α, and IL-17 in the cerebrospinal fluid of rats. The GC-TOFMS was used to detect the changes of glycolytic metabolites in the cerebrospinal fluid of rats. EZH2 could mediate inflammation and glycolysis of microglia. EZH2 regulates inflammation and glycolysis through HIF-1α. EZH2 indirectly regulated the HIF-1α expression by mediating miR-146a-5p. EZH2 mediates miR-146a-5p/HIF-1α to alleviate inflammation and glycolysis in ASCI rats. In the present study, our results demonstrated that EZH2 could mediate miR-146a-5p/HIF-1α to alleviate the inflammation and glycolysis after ASCI. Therefore, EZH2/miR-146a-5p/HIF-1α might be a novel potential target for treating ASCI.

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

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.

scholarly journals Targeting the NLRP3 inflammasome to attenuate spinal cord injury in mice

2017 ◽  
Vol 14 (1) ◽  
Author(s):  
Wu Jiang ◽  
Maoqiang Li ◽  
Fan He ◽  
Shaobo Zhou ◽  
Liulong Zhu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Nlrp3 Inflammasome ◽  
Cord Injury

scholarly journals Molecular Mechanism of MiR-136-5p Targeting NF-κB/A20 in the IL-17-Mediated Inflammatory Response after Spinal Cord Injury

2017 ◽  
Vol 44 (3) ◽  
pp. 1224-1241 ◽  
Author(s):  
Jichen He ◽  
Jinmin Zhao ◽  
Xiaoming Peng ◽  
Xiongzhi Shi ◽  
Shaohui Zong ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Factors ◽  
Scoring Method ◽  
Histological Changes ◽  
Cord Injury ◽  
Rat Astrocytes ◽  
Underlying Mechanisms

Background/Aims: The pathophysiology of spinal cord injury (SCI) results in serious damage to the human body via an increase in the secondary biological processes imposed by activated astrocytes. Abnormal expression of microRNAs after SCI has become a potential research focus. However, the underlying mechanisms are poorly understood. Methods: SCI models were established in rats using Allen’s method, and the BBB scoring method was employed to assess locomotor function. Lentivirus was used to infect rat astrocytes and SCI rats. Real-time PCR and antibody chip were used to measure gene expression and cytokine secretion. Western blot analysis was employed to detect protein expression. HE staining was used to assess the histological changes in SCI. The immunohistochemical staining of A20 and p-NF-κB in SCI was also analyzed. Results: The in vitro experiment showed that miR-136-5p up-regulated the expression of p-NF-κB by down-regulating the expression of A20 so that astrocytes produced inflammatory factors and chemokines. The in vivo experiment indicated that overexpressed miR-136-5p promoted the production of inflammatory factors, chemokines and p-NF-κB in SCI rats, whereas it inhibited the expression of A20 protein and increased inflammatory cell infiltration and injuries in the spinal cord. Conclusion: The current findings indicate that silencing miR-136-5p effectively decreased inflammatory factors and chemokines and protected the spinal cord via NF-κB/A20 signaling in vivo and in vitro. In contrast, overexpression of miR-136-5p had the opposite effect.

Acupuncture for Treatment of Secondary Osteoporosis in Patients with Spinal Cord Injury: A Controlled Study

2014 ◽  
Vol 32 (5) ◽  
pp. 381-386 ◽  
Author(s):  
Qingxi Meng ◽  
Xin Liu ◽  
Qunqun Shan ◽  
Peng Yu ◽  
Zhaohu Mao ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Combination Therapy ◽  
Bone Mineral ◽  
Secondary Osteoporosis ◽  
Mineral Density ◽  
Cord Injury ◽  
Group 2 ◽  
Group 1

Objective We explored the effect of adjunctive acupuncture on secondary osteoporosis in patients with spinal cord injury (SCI). Methods Patients with subacute SCI were recruited and divided into two groups by patient choice: group 1 patients received standard combination therapy and group 2 patients received combination therapy plus acupuncture for 3 months. The concentrations of IgG, IgM and tumour necrosis factor α (TNFα) in serum and the bone mineral density were measured before and after treatment. Result The decrease in the concentration of TNFα and IgM in patients in group 2 compared with those in group 1 was statistically significant. The IgG level showed no significant change in either group. Bone mineral density increased more after adjunctive acupuncture, but the difference was not significant. Conclusions Further research is needed to determine whether acupuncture as an adjunct to combination therapy can reduce osteoporosis in patients with subacute SCI. Trial Registration Number P153-2008-36

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