scholarly journals Overexpression of the transcription factors OCT4 and KLF4 improves motor function after spinal cord injury

2020 ◽  
Vol 26 (9) ◽  
pp. 940-951
Author(s):  
Xianpeng Huang ◽  
Chenggui Wang ◽  
Xiaopeng Zhou ◽  
Jingkai Wang ◽  
Kaishun Xia ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Transcription Factors ◽  
Motor Function ◽  
Cord Injury

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.

Adequate expression of neuropeptide Y is essential for the recovery of zebrafish motor function following spinal cord injury

2021 ◽  
pp. 113831
Author(s):  
Chun Cui ◽  
Lin-Fang Wang ◽  
Shu-Bing Huang ◽  
Peng Zhao ◽  
Yong-Quan Chen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropeptide Y ◽  
Motor Function ◽  
Cord Injury

scholarly journals Photobiomodulation Promotes Repair Following Spinal Cord Injury by Regulating the Transformation of A1/A2 Reactive Astrocytes

2021 ◽  
Vol 15 ◽  
Author(s):  
Xuankang Wang ◽  
Zhihao Zhang ◽  
Zhijie Zhu ◽  
Zhuowen Liang ◽  
Xiaoshuang Zuo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Growth Factor ◽  
Motor Function ◽  
Function Analysis ◽  
Reactive Astrocytes ◽  
Male Rats ◽  
Dependent Manner ◽  
Astrocyte Activation ◽  
Cord Injury

After spinal cord injury (SCI), reactive astrocytes can be classified into two distinctive phenotypes according to their different functions: neurotoxic (A1) astrocytes and neuroprotective (A2) astrocytes. Our previous studies proved that photobiomodulation (PBM) can promote motor function recovery and improve tissue repair after SCI, but little is known about the underlying mechanism. Therefore, we aimed to investigate whether PBM contributes to repair after SCI by regulating the activation of astrocytes. Male rats subjected to clip-compression SCI were treated with PBM for two consecutive weeks, and the results showed that recovery of motor function was improved, the lesion cavity size was reduced, and the number of neurons retained was increased. We determined the time course of A1/A2 astrocyte activation after SCI by RNA sequencing (RNA-Seq) and verified that PBM inhibited A1 astrocyte activation and promoted A2 astrocyte activation at 7 days postinjury (dpi) and 14 dpi. Subsequently, potential signaling pathways related to A1/A2 astrocyte activation were identified by GO function analysis and KEGG pathway analysis and then studied in animal experiments and preliminarily analyzed in cultured astrocytes. Next, we observed that the expression of basic fibroblast growth factor (bFGF) and transforming growth factor-β (TGF-β) was upregulated by PBM and that both factors contributed to the transformation of A1/A2 astrocytes in a dose-dependent manner. Finally, we found that PBM reduced the neurotoxicity of A1 astrocytes to dorsal root ganglion (DRG) neurons. In conclusion, PBM can promote better recovery after SCI, which may be related to the transformation of A1/A2 reactive astrocytes.

scholarly journals Intraspinal Injection of Platelet-Rich Plasma Promotes Regeneration of the Spinal Cord and Improves Locomotor Function by Modulating the Apoptosis and the Wnt Signaling Pathways

2021 ◽  
Author(s):  
Zahra Behroozi ◽  
Fatemeh Ramezani ◽  
farinaz Nasirinezhad
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Wnt Signaling ◽  
Motor Function ◽  
Platelet Rich Plasma ◽  
Wnt Signaling Pathway ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Locomotor Function ◽  
Cord Injury

Abstract Background: There are complex mechanisms for reducing intrinsic repair ability and neuronal regeneration following spinal cord injury (SCI). Platelet-rich plasma (PRP) is a rich source of growth factors and has been used to stimulate regeneration of peripheral nerves in degenerationtive diseases. However, only a few studies have investigated the effects of PRP on the SCI models. We examined whether PRP derived from human umbilical cord blood (HUCB-PRP) could recover motor function in animals with spinal cord injury. We also investigate the role of Wnt signaling pathway.Methods: Ault male Wistar rats were randomly divided into 6 groups (n=60) as control, sham, SCI, vehicle (SCI+platelet-poor plasma), PRP2day (SCI+injection 2 days after SCI) and PRP14day (SCI+injection 14 days after SCI). SCI was performed at the T12-T13 level. BBB tests were done weekly after injury for six weeks. caspase3 expression was determined using the Immunohistochemistry technique. The expression of GSK3β, Tau and MAG were determined using the Western blot technique. Data were analyzed by PRISM & SPSS software. Results: PRP injected animals showed a higher locomotor function recovery than those in the SCI group (p<0.0001). The level of caspase3, GSK3β and CSF- Tau reduced and MAG level in the spinal cord increased by injection of HUCB-PRP in animals with spinal cord injury. Conclusions: Injection of HUCB-PRP enhanced hind limb locomotor performance by modulation of caspase3, GSK3β, tau and MAG expression. Using HUCB-PRP could be a new therapeutic option for recovering the motor function and axonal regeneration after spinal cord injury.

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