scholarly journals miRNA-221 Regulates Spinal Cord Injury-Induced Inflammatory Response through Targeting TNF-α Expression

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Feng Sun ◽  
Haiwei Zhang ◽  
Tianwen Huang ◽  
Jianhui Shi ◽  
Tianli Wei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Mouse Model ◽  
Luciferase Reporter ◽  
Spinal Cord Tissue ◽  
Tnf Α ◽  
Cord Injury ◽  
And Oxidative Stress

Objectives. To investigate the roles of miR-221 in spinal cord injury (SCI) as well as the underlying mechanism. Methods. A mouse model of SCI was generated and used to examine dynamic changes in grip strength of the mouse upper and lower limbs. The expression of miR-221 and tumor necrosis factor-α (TNF-α) was detected by RT-qPCR and Western blot. Levels of inflammation and oxidative stress in microglia cells of the injured mice overexpressing miR-221 were then measured by ELISA. Bioinformatics analysis and dual-luciferase reporter assay were conducted to identify the miR-221 target. Results. We successfully constructed SCI mouse model. The results of qRT-PCR showed that miR-221 was gradually upregulated in the spinal cord tissue of mice in the SCI group with the prolonged injury time. At the same time, the mRNA and protein of TNF-α gradually decreased. We further confirmed through cell experiments that the inflammatory factors TNF-α and IL-6, as well as iNOS and eROS, were upregulated in spinal cord microglia cells of SCI mice, and upregulation of miR-122 can inhibit their expression. Finally, the luciferase reporter experiment confirmed that miR-122 targeted TNF-α. Conclusions. We present evidence that miR-221 promotes functional recovery of the injured spinal cord through targeting TNF-α, while alleviating inflammatory response and oxidative stress.

Effect of Electroacupuncture on Spinal Cord Injury in Mice: Inhibition Of Inflammatory Response and Oxidative Stress via ApoE and Nrf2

2020 ◽  
Author(s):  
Ni Dai ◽  
Chenglin Tang ◽  
Hongdi Zhao ◽  
Pan Dai ◽  
Siqin Huang
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Neuroprotective Effect ◽  
Related Factor ◽  
Cord Injury ◽  
Anti Inflammatory ◽  
And Oxidative Stress

Abstract Background: Spinal cord injury (SCI) is a catastrophic central nervous system disease. Inflammatory response and oxidative stress are two critical factors in the pathophysiological process of SCI and closely involved with Apolipoprotein E(ApoE) and Nuclear factor erythroid 2-related factor (Nrf2). Electroacupuncture (EA) has perfectly neuroprotective effect on SCI. However, the underlying mechanism by which EA mediates the inflammatory response and oxidative stress is not completely elucidated. In the present study, we investigated the signaling pathways that EA regulates inflammatory response and oxidative stress through elevation of ApoE and Nrf2 after SCI.Methods: C57BL/6 Wide Type (WT) mice and ApoE -/- mice were subjected to SCI model by a serrefine clamping. Neurological function was detected by BMS scores, ultrastructure of demyelinationed axons was observed by transmission electron microscopy. ApoE, pro- and anti- inflammatory cytokines, oxidative stress-relevant proteins were determined by histochemistry technology. Two-way ANOVA was applied to BMS scores. One-way ANOVA and Bonferroni's multiple comparison test were used to analyse differences among groups.Results: BMS scores were increased gradually and demyelinated axons were improved by EA gradually with the expression of ApoE. EA can inhibit inflammatory response by activation of ApoE, which decreased pro-inflammatory cytokines(TNF-α, IL-6, and IL-1β) expression and increased anti-inflammatory cytokines(IL-10 and TGF-β1).Meanwhile, EA can also inhibit oxidative stress by elevation of Nrf2,which induced HO-1 and NQO1 expression in WT and ApoE -/- mice.Conclusions: EA is a reliable treatment for promoting functional recovery of SCI. Thesynergisticrole of ApoE and Nrf2 in EA regulating inflammatory response and oxidative stress is decisiveto recovery after SCI.

Therapeutic targets and nanomaterial-based therapies for mitigation of secondary injury after spinal cord injury

Nanomedicine ◽  
2021 ◽  
Vol 16 (22) ◽  
pp. 2013-2028
Author(s):  
Jun Gao ◽  
Minkyung Khang ◽  
Zhen Liao ◽  
Megan Detloff ◽  
Jeoung Soo Lee
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Therapeutic Targets ◽  
Neurological Dysfunction ◽  
Secondary Injury ◽  
Cord Injury ◽  
Blood Spinal Cord Barrier ◽  
And Oxidative Stress

Spinal cord injury (SCI) and the resulting neurological trauma commonly result in complete or incomplete neurological dysfunction and there are few effective treatments for primary SCI. However, the following secondary SCI, including the changes of microvasculature, inflammatory response and oxidative stress around the injury site, may provide promising therapeutic targets. The advances of nanomaterials hold promise for delivering therapeutics to alleviate secondary SCI and promote functional recovery. In this review, we highlight recent achievements of nanomaterial-based therapy, specifically targeting blood–spinal cord barrier disruption, mitigation of the inflammatory response and lightening of oxidative stress after spinal cord injury.

scholarly journals Long noncoding RNA MALAT1 contributes to inflammatory response of microglia following spinal cord injury via the modulation of a miR-199b/IKKβ/NF-κB signaling pathway

2018 ◽  
Vol 315 (1) ◽  
pp. C52-C61 ◽  
Author(s):  
Heng-Jun Zhou ◽  
Li-Qing Wang ◽  
Duan-Bu Wang ◽  
Jian-Bo Yu ◽  
Yu Zhu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Proinflammatory Cytokines ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Tnf Α ◽  
Cord Injury

Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was widely recognized to be implicated in human cancer, vascular diseases, and neurological disorders. This study was to explore the role and underlying mechanism of MALAT1 in acute spinal cord injury (ASCI). ASCI models in adult rats were established and demonstrated by a numerical decrease in BBB scores. Expression profile of MALAT1 and miR-199b following ASCI in rats and in vitro was determined using quantitative real-time PCR. RNA pull-down assays combined with RIP assays were performed to explore the interaction between MALAT1 and miR-199b. In the present study, MALAT1 expression was significantly increased (2.4-fold that of control) in the spinal cord of the rat contusion epicenter accompanied by activation of IKKβ/NF-κB signaling pathway and an increase in the level of proinflammatory cytokines TNF-α and IL-1β. Upon treatment with LPS, MALAT1 expression dramatically increased in the microglia in vitro, but knockdown of MALAT1 attenuated LPS-induced activation of MGs and TNF-α and IL-1β production. Next, we confirmed that LPS-induced MALAT1 activated IKKβ/NF-κB signaling pathway and promoted the production of proinflammatory cytokines TNF-α and IL-1β through downregulating miR-199b. More importantly, MALAT1 knockdown gradually improved the hindlimb locomotor activity of ASCI rats as well as inhibited TNF-α, IL-1β levels, and Iba-1 protein, the marker of activated microglia in injured spinal cords. Our study demonstrated that MALAT1 was dysregulated in ASCI rats and in LPS-activated MGs, and MALAT1 knockdown was expected to attenuate ASCI through repressing inflammatory response of MGs.

scholarly journals Catalpol Protects Against Spinal Cord Injury in Mice Through Regulating MicroRNA-142-Mediated HMGB1/TLR4/NF-κB Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Hougang Xia ◽  
Dandan Wang ◽  
Xiaohui Guo ◽  
Kaidi Wu ◽  
Fuwei Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Inflammatory Factors ◽  
Tunel Staining ◽  
Ros Generation ◽  
Bv2 Cells ◽  
Cord Injury ◽  
Oxidative Response

Background: Spinal cord injury (SCI) is a devastating condition that leads to paralysis, disability and even death in severe cases. Inflammation, apoptosis and oxidative stress in neurons are key pathogenic processes in SCI. Catalpol (CTP), an iridoid glycoside extracted from Rehmannia glutinosa, has many pharmacological activities, such as anti-inflammatory, anti-oxidative and anti-apoptotic properties.Purpose: Here, we investigated whether CTP could exert neuroprotective effects against SCI, and explored the underlying mechanism involved.Methods: SCI was induced by a weight-drop device and treated with CTP (10 mg and 60 mg/kg). Then the locomotor function of SCI mice was evaluated by the BBB scores, spinal cord edema was measured by the wet/dry weight method, oxidative stress markers and inflammatory factors were detected by commercial kits and neuronal death was measured by TUNEL staining. Moreover, the microRNA expression profile in spinal cords from mice following SCI was analyzed using miRNA microarray. In addition, reactive oxygen species (ROS) generation, inflammatory response and cell apoptosis were detected in murine microglia BV2 cells under oxygen-glucose deprivation (OGD) and CTPtreatment.Results: Our data showed that CTP treatment could improve the functional recovery, as well as suppress the apoptosis, alleviate inflammatory and oxidative response in SCI mice. In addition, CTP was found to be up-regulated miR-142 and the protective effects of CTP on apoptosis, inflammatory and oxidative response may relate to its regulation of HMGB1/TLR4/NF-κB pathway through miR-142.Conclusion: Our findings suggest that CTP may protect the spinal cord from SCI by suppression of apoptosis, oxidative stress and inflammatory response via miR-142/HMGB1/TLR4/NF-κB pathway.

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