scholarly journals The Repression of the HMGB1-TLR4-NF-κB Signaling Pathway by Safflower Yellow May Improve Spinal Cord Injury

2021 ◽  
Vol 15 ◽  
Author(s):  
Lu Wang ◽  
Benson O. A. Botchway ◽  
Xuehong Liu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Nerve Tissue ◽  
Inflammatory Factors ◽  
Spinal Cord Tissue ◽  
Pathophysiological Mechanism ◽  
Cord Injury

Spinal cord injury (SCI) often results in abnormal sensory and motor functions. Current interventions for SCI in the clinical setting are not effective partly due to the complexity concerning its pathophysiological mechanism. In the wake of SCI, considerable inflammatory cells assemble around the injured area that induces a series of inflammatory reactions and aggravates tissue lesions, thereby affecting the recovery of the damaged nerve tissue. Therefore, the inhibition of inflammatory responses can improve the repair of the injured spinal cord tissue. Safflower Yellow (SY) is the main active ingredient of Carthamus tinctorius. SY has anti-inflammatory effect, as it can inhibit IκBα phosphorylation to impede the NF-κB signaling pathway and p53 nuclear translocation. Besides, SY can limit the release of pro-inflammatory factors, which in turn may alleviate secondary SCI and prevent further complications. In this report, we analyze the pathophysiological mechanism of SCI, the role of inflammatory responses, and how SY interferes with the HMGB1-TLR-4-NF-κB signaling pathway to attenuate inflammatory responses in SCI.

scholarly journals Preparation of Drug Sustained-Release Scaffold with De-Epithelized Human Amniotic Epithelial Cells and Thiolated Chitosan Nanocarriers and Its Repair Effect on Spinal Cord Injury

2022 ◽  
Vol 2022 ◽  
pp. 1-8
Author(s):  
Lijuan Zhu ◽  
Shaohua Tian ◽  
Zhiyong Li ◽  
Dandan Fan ◽  
Hongwei Gao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Survival Rate ◽  
Inflammatory Factors ◽  
Spinal Cord Tissue ◽  
Thiolated Chitosan ◽  
Cord Injury ◽  
Human Amniotic Epithelial Cells

The disability rate of spinal cord injury (SCI) is extremely high, and stem cell inhibition is one of the most effective schemes in treating the spinal cord, but the survival rate is extremely low after stem cell transplantation, so it cannot be widely used in clinic. Studies have revealed that loading stem cells with biological scaffolds can effectively improve the survival rate and effect after stem cell transplantation. Therefore, this research was devised to analyze the repair effect of thiolated chitosan nanocarriers scaffold carrying de-epithelized human amniotic epithelial cells (HAECs) on SCI. And we used thiolated chitosan as nanocarriers, aiming to provide a reliable theoretical basis for future clinical practice. Through experiments, we concluded that the Tarlov and BBB scores of rats with SCI were raised under the intervention of thiolated chitosan carrying HAECs, while the inflammatory factors in serum, oxidative stress reaction in spinal cord tissue, apoptosis rate of nerve cells, and autophagy protein expression were all suppressed. Thus, the thiolated chitosan carrying HAECs may be applied to treat SCI by suppressing autophagy protein expression, oxidative stress response, and release of inflammatory factors in spinal cord tissue, which may be a new clinical therapy for SCI in the future. Even though we cannot understand exactly the therapeutic mechanism of thiolated chitosan carrying HAECs for SCI, the real clinical application of thiolated chitosan carrying HAECs needs to be confirmed by human experiments.

Critical role of microglia in the inflammatory response after spinal injury

2015 ◽  
Vol 3 (3) ◽  
pp. 453-462
Author(s):  
Ya-Yun Shi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Responses ◽  
Spinal Injury ◽  
Critical Role ◽  
Cell Types ◽  
Inflammatory Factors ◽  
Cytokines And Chemokines ◽  
Cord Injury

Spinal cord injury induces a robust neuroinflammatory response that includes marked changes in the variety of endogenous CNS cell types specially microglia. In response to spinal injury, microglia undergo dramatic changes in cell morphology and promote inflammatory responses, which result in production of inflammatory factors and oxidative stress including reactive oxygen species. Further pro-inflammatory cytokines and chemokines are also rapidly up-regulated and likely contribute to microglial activation. This topic review will explore the current research on microglial responses to spinal injury and the recent progress in the pharmacologic and molecular targeting of microglia in spinal injury. Finally, we explore the argument for a positive versus negative role of microglia after spinal cord injury.

scholarly journals Modulation of inflammatory factors predicts the outcome following spinal cord injury

2020 ◽  
Author(s):  
Zepeng Yu ◽  
Xingwei Sun ◽  
Rui Xia ◽  
Qian Chen ◽  
Qin Wu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axonal Regeneration ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Serum Levels ◽  
High Serum ◽  
Inflammatory Factors ◽  
Mhc I ◽  
Cord Injury

Abstract BACKGROUND : The correlation between inflammatory responses caused by spinal cord injury (SCI) and the prognosis of patients with SCI still remains controversial. METHODS : In the present study, we preliminary investigated the serum levels of interleukin (IL)-4, IL-10, major histocompatibility complex (MHC)-I and inducible nitric oxide synthase (iNOS), and compared the serum IL-4 and IL-10 expression in rats of high BBB scores with these of low Basso-Beattie-Bresnahan(BBB) scores. Besides, the infiltration of macrophage and the axonal regeneration of the injuried spinal cord were observed from day10 to day30. RESULTS : We found that higher serum levels of IL-4 and IL-10 can reflect the restorability degree of SCI and could be potential biomarkers for the prognosis of SCI. The infiltration of M2 subtype of macrophage and the axons regrowth might contribute to better prognosis. CONCLUSIONS ： Collectively, the current study demonstrates that the serum levels of IL-4 and IL-10 are preliminary adopted as serologic markers to forecast SCI, and high serum levels of IL-4 and IL-10 may indicate a better prognosis. Moreover, the way to promote macrophage polarization from M1 to M2 may contribute to better axonal regeneration.

Therapeutic Effects of Azithromycin on Spinal Cord Injury in Male Wistar Rats: A Role for Inflammatory Pathways

2021 ◽  
Author(s):  
Ali Rismanbaf ◽  
Khashayar Afshari ◽  
Mehdi Ghasemi ◽  
Abolfazl Badripour ◽  
Arvin Haj-Mirzaian ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Wistar Rats ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Therapeutic Effects ◽  
Spinal Cord Tissue ◽  
Cord Injury ◽  
Male Wistar Rats

Abstract Background Inflammatory responses, including macrophages/microglia imbalance, are associated with spinal cord injury (SCI) complications. Accumulating evidence also suggests an anti-inflammatory property of azithromycin (AZM). Material and Methods Male Wistar rats were subjected to T9 vertebra laminectomy. SCI was induced by spinal cord compression at this level with an aneurysmal clip for 60 seconds. They were divided into three groups: the sham-operated group and two SCI treatment (normal saline as a vehicle control vs. AZM at 180 mg/kg/d intraperitoneally for 3 days postsurgery; first dose: 30 minutes after surgery) groups. Locomotor scaling and behavioral tests for neuropathic pain were evaluated and compared through a 28-day period. At the end of the study, tissue samples were taken to assess neuroinflammatory changes and neural demyelination using ELISA and histopathologic examinations, respectively. In addition, the proportion of M1/M2 macrophage polarization was assessed by using flow cytometry. Results Post-SCI AZM treatment (180 mg/kg/d for 3 days) significantly improved locomotion (p < 0.01) and decreased sensitivity to mechanical (p < 0.01) and thermal allodynia (p < 0.001). Moreover, there was a significant tumor necrosis factor-α (TNF-α) decline (p < 0.01) and interleukin-10 (IL-10) elevation (p < 0.01) in the spinal cord tissue of the AZM-treated group compared with the control groups 28 days post-SCI. AZM significantly improved neuroinflammation as evidenced by reduction of the M1 expression, elevation of M2 macrophages, and reduction of the M1/M2 ratio in both the dorsal root ganglion and the spinal cord tissue after SCI compared with controls (p < 0.01). Conclusion AZM treatment can be considered a therapeutic agent for SCI, as it could reduce neuroinflammation and SCI sensory/locomotor complications.

scholarly journals Effect of Electroacupuncture Treatment at Dazhui (GV14) and Mingmen (GV4) Modulates the PI3K/AKT/mTOR Signaling Pathway in Rats after Spinal Cord Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Ke Li ◽  
Juntong Liu ◽  
Liangyu Song ◽  
Wei Lv ◽  
Xi Tian ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Sham Operation ◽  
Spinal Cord Tissue ◽  
Group Model ◽  
Injured Spinal Cord ◽  
Mtor Signaling Pathway ◽  
Cord Injury

Electroacupuncture (EA) is widely recognized as clinical treatment of spinal cord injury (SCI). The purpose of this study is to elucidate whether and how the PI3K/AKT/mTOR signaling pathway plays any role in EA treating SCI. Rats were randomly divided into four equal groups: Control Group, Sham-operation Group, Model Group, and EA Group, then further randomly divided into the following subgroups: 1-day (n=12), 1-day rapamycin (n=6), 14-day (n=18), and 28-day (n=18). A rat model of SCI was established by a modified Allen’s weight-drop method. In the EA Group, rats were stimulated on Dazhui (GV14) and Mingmen (GV4) for 20 min by sterilized stainless steel needles. In the EA Group, the Basso, Beattie, and Bresnahan locomotor rating scale showed obvious improved locomotor function, and hematoxylin-eosin staining and magnetic resonance imaging showed that the histological morphology change of injured spinal cord tissue was obviously alleviated. Also, blocking spinal mTOR by injection of rapamycin showed that mTOR existed in the injured spinal cord, and EA could significantly activate mTOR in SCI rats. And immunohistochemistry and western blot analysis on the PI3K/AKT/mTOR signaling pathway showed that levels of PI3K, AKT, mTOR, and p70S6K in the injured spinal cord tissue were greatly increased in the EA Group, while the levels of PTEN and caspase 3 were decreased. The present study suggests that EA could affect cell growth, apoptosis, and autophagy through the PI3K/AKT/mTOR signaling pathway.

scholarly journals Modulation of inflammatory factors predicts the outcome following spinal cord injury

2020 ◽  
Author(s):  
Zepeng Yu ◽  
Xingwei Sun ◽  
Rui Xia ◽  
Qian Chen ◽  
Qin Wu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axonal Regeneration ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Serum Levels ◽  
High Serum ◽  
Inflammatory Factors ◽  
Mhc I ◽  
Cord Injury

Abstract BACKGROUND: The correlation between inflammatory responses caused by spinal cord injury (SCI) and the prognosis of patients with SCI still remains controversial.METHODS: In the present study, we preliminary investigated the serum levels of interleukin (IL)-4, IL-10, major histocompatibility complex (MHC)-I and inducible nitric oxide synthase (iNOS), and compared the serum IL-4 and IL-10 expression in rats of high Basso-Beattie-Bresnahan (BBB) scores with these of low BBB scores. Besides, the infiltration of macrophage and the axonal regeneration of the injured spinal cord were observed from day10 to day30.RESULTS: We found that higher serum levels of IL-4 and IL-10 can reflect the restorability degree of SCI and could be potential biomarkers for the prognosis of SCI. The infiltration of the M2 subtype of macrophage and the axons regrowth might contribute to a better prognosis.CONCLUSIONS：The current study demonstrates that the serum levels of IL-4 and IL-10 are preliminary adopted as serologic markers to forecast SCI, and high serum levels of IL-4 and IL-10 may indicate a better prognosis. Moreover, the way to promote macrophage polarization from M1 to M2 may contribute to better axonal regeneration.

scholarly journals Gut Microbiota Disorders Promote Inflammation and Aggravate Spinal Cord Injury Through the TLR4/MyD88 Signaling Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Zijie Rong ◽  
Yuliang Huang ◽  
Honghua Cai ◽  
Min Chen ◽  
Hao Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Gut Microbiota ◽  
Signaling Pathway ◽  
Nerve Cells ◽  
Inflammatory Factors ◽  
Arginase 1 ◽  
Cord Injury ◽  
Anti Inflammatory ◽  
Myd88 Signaling

Background: In spinal cord injury (SCI), systemic inflammation and the death of nerve cells in the spinal cord are life threatening. The connection between gut microbiota and signaling pathways has been a hot research topic in recent years. The Toll-like receptor 4/Myeloid differentiation factor 88 (TLR4/MyD88) signaling pathway is closely related to the inflammatory response. This study explored whether the gut microbiota imbalance could affect the TLR4/MyD88 signaling pathway to regulate SCI to provide a new basis for SCI research and treatment.Methods: An SCI model was constructed to study the influence on the injury of gut microbiota. 16S amplicon sequencing was used to identify the diversity and abundance of gut microbes. Fecal microbiota transplantation was performed in mice with SCI. ELISA was used to detect the serum levels of pro-inflammatory and anti-inflammatory factors in mice. Hematoxylin and eosin staining was used to observe SCI in mice. Immunofluorescence was used to detect the rates of loss glial fibrillary acidic protein (GFAP), neuronal nuclear protein (NeuN), and ionized calcium-binding adapter molecule 1 (IBA1) in the spinal cord as indicators of apoptosis. The expression of the TLR4/MyD88 signaling pathway was detected by qRT-PCR and western blotting.Results: Significant differences were observed in the gut microbiota of SCI mice and normal mice. The gut microbiota of SCI mice was imbalanced. The levels of pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in SCI mice were increased, as was the level of the toxic induced nitric oxide synthase. The levels of anti-inflammatory factors IL-4, transforming growth factor-β, and IL-10 were decreased, as was the level of arginase-1. The apoptosis rates of GFAP, NeuN, and IBA1 were increased. The TLR4/MyD88 signaling pathway was activated. In the SCI group, inflammation increased after fecal transplantation, apoptosis of GFAP, NeuN, and IBA1 increased, and SCI was more serious.Conclusion: The TLR4/MyD88 signaling pathway promotes the death of nerve cells by inducing inflammation. Gut microbiota dysregulation can lead to aggravated SCI by activating the TLR4/MyD88 signaling pathway.

Interference of interleukin-1β mediated by lentivirus promotes functional recovery of spinal cord contusion injury in rats via the PI3K/AKT signaling pathway

2020 ◽  
Author(s):  
Yi-li Wang ◽  
Xi Hu ◽  
Qin-xuan Li ◽  
Li-xin Zhang ◽  
Qing-jie Xia ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signaling Pathway ◽  
Motor Function ◽  
Akt Signaling ◽  
Inflammatory Factors ◽  
Akt Signaling Pathway ◽  
Cord Injury ◽  
Spinal Cord Contusion ◽  
Recovery Of Motor Function

Abstract Background: Spinal cord contusion (SCC) results in a series of pathophysiologic consequences such as edema, apoptosis, and inflammation. However, inflammation may also be beneficial for the recovery of motor function after SCC, but the underlying mechanisms remain incompletely elucidated. Interleukin-1 beta (IL-1β) is a pro-inflammatory factor that has synergistic effects with other inflammatory factors to aggravate spinal cord injury. Inflammatory factors have been found to activate the serine/threonine-specific protein kinase, protein kinase B (AKT) and to inhibit cell survival, but it is not clear whether inflammation upregulates the expression of IL-1β in the rat model of SCC and subsequently interferes in the phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathway. Therefore, this study explored whether IL-1β affects the recovery of motor function in spinal cord injury by interfering with the PI3K/AKT signaling pathway. Method: SCC rats were established by the Allen method. The Basso Beattie Bresnahan (BBB) scoring was used to assess motor function in the spinal cord of injured rats. Quantitative polymerase chain reaction and Western blot were used to determine the expression of genes and proteins of IL-1β, PI3K, and AKT1. Immunohistochemistry and immunofluorescence were used to locate and detect IL-1β and AKT1 proteins in spinal cord tissue. To further explore the underlying mechanism of IL-1β, lentivirus was constructed by RNA interfering (RNAi) technique to inhibit the expression of IL-1β, and bioinformatics was applied to show the relationship between IL-1β and AKT1. Results: BBB scores decreased after SCC, and IL-1β and AKT1 was located in the cytoplasm of spinal cord anterior horn neurons. In the early stage of SCC, the expression level of IL-1β gene and protein in the experimental group was higher than that in the sham operated group. At the same time, expression of the AKT1 gene decreased. After expression of IL-1β mediated by lentivirus was inhibited, BBB scores increased significantly, and spinal cord motor function improved. Bioinformatic analysis revealed a relationship between IL-1β and AKT1. In addition, AKT1 gene expression was upregulated and PI3K expression was unchanged in the PI3K/AKT signaling pathway. Conclusion IL-1β not only exacerbates the inflammatory response after SCC, but also interferes with motor function. Inhibition of IL-1β may promote recovery of spinal cord injury by upregulating AKT1 in the PI3K/AKT signaling pathway, which provides a new perspective for future clinical practice in treating spinal cord injury

The Regulation of Bone Morphogenetic Protein/Smads Signaling Pathway in Spinal Cord Injury

2020 ◽  
Vol 10 (3) ◽  
pp. 323-328
Author(s):  
Zhigang Zhou ◽  
Kai Cao ◽  
Jianping Liao ◽  
Song Zhou ◽  
Liangliang Zhou ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Treatment Group ◽  
Signaling Pathway ◽  
Rating Scale ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Spinal Cord Tissue ◽  
Cord Injury ◽  
Smad5 Mrna

The incidence of spinal cord injury (SCI) increases year by year. SCI is characterized as high disability rate and poor prognosis. BMP/Smads signaling participates in the formation of osteoblasts and renal failure. This article will explore the regulation of BMP/Smads signaling pathway in SCI. Wistar rats were divided into control group; SCI group; and BMP-2 treatment group that were treated by tail vein injection of BMP-2 antisense oligonucleotide BMP-2 phosphorothioate AODN at 30 min after modeling. Real-time PCR and Western blot were used to detect BMP-2, Smad1, and Smad5 expressions. Hematoxylin-eosin (HE) staining was applied to analyze the change of SCI in each group. Immunohistochemistry (IHC) was selected to test BMPR Ia expression. Basso, Beattie Bresnahan-cocomotor rating scale (BBB) scale and Reuter score were compared. Enzyme-linked immunosorbent assay (ELISA) was adopted to detect TNF-α and Interleukin-2 (IL-2) expressions. Compared with the control group, BMP-2, Smad1, and Smad5 mRNA and protein expressions increased, BBB score declined, Reuter score elevated, and TNF-α and IL-2 secretion enhanced in the SCI group (P < 0.05). HE staining showed spinal cord injury, and IHC exhibited increased expression of BMPR Ia. The TGF-β treatment group significantly reduced the expressions of BMP-2, Smad1, and Smad5 mRNA and protein, increased BBB score, reduced Reuter score, and weakened the secretions of TNF-α and IL-2 (P < 0.05). HE staining demonstrated decreased reduction of spinal cord tissue and declined expression of BMPR Ia. SCI activated BMP/Smads signaling pathway, up-regulated BMPR Ia expression, and promoted inflammation. Regulation of BMP/Smads signaling pathway can downregulate BMPR Ia expression and inhibit inflammation to effectively relieve SCI.

Antithrombin reduces the ischemia/reperfusion-induced spinal cord injury in rats by attenuating inflammatory responses

2004 ◽  
Vol 91 (01) ◽  
pp. 162-170 ◽  
Author(s):  
Koji Hirose ◽  
Yuji Taoka ◽  
Mitsuhiro Uchiba ◽  
Kan-yu Nakano ◽  
Junichi Utoh ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Neurons ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Spinal Cord Tissue ◽  
Protective Effects ◽  
Tissue Levels ◽  
Cord Injury

SummaryAntithrombin (AT) reveals its antiinflammatory activity by promoting endothelial release of prostacyclin (PGI2) in vivo. Since neuroinflammation is critically involved in the development of ischemia/reperfusion (I/R)-induced spinal cord injury (SCI), it is possible that AT reduces the I/R-induced SCI by attenuating the inflammatory responses. We examined this possibility using rat model of I/R-induced SCI in the present study. AT significantly reduced the mortality and motor disturbances by inhibiting reduction of the number of motor neurons in animals subjected to SCI. Microinfarctions of the spinal cord seen after reperfusion were markedly reduced by AT. AT significantly enhanced the I/R-induced increases in spinal cord tissue levels of 6-keto-PGF1α, a stable metabolite of PGI2. AT significantly inhibited the I/R-induced increases in spinal cord tissue levels of TNF-α, rat interleukin-8 and myeloperoxidase. In contrast,Trp49-modified AT did not show any protective effects. Pretreatment with indomethacin significantly reversed the protective effects of AT.An inactive derivative of factor Xa, which selectively inhibits thrombin generation, has been shown to fail to reduce SCI.Taken together, these observations strongly suggested that AT might reduce I/R-induced SCI mainly by the antiinflammatory effect through promotion of endothelial production of PGI2. These findings also suggested that AT might be a potential neuroprotective agent.

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