scholarly journals Protective Effects of CISD2 and Influence of Curcumin on CISD2 Expression in Aged Animals and Inflammatory Cell Model

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 700 ◽  
Author(s):  
Chai-Ching Lin ◽  
Tien-Huang Chiang ◽  
Yu-Yo Sun ◽  
Muh-Shi Lin
Keyword(s):  
Spinal Cord ◽  
Mitochondrial Dysfunction ◽  
Cell Model ◽  
Neural Cells ◽  
Protective Effects ◽  
Curcumin Treatment ◽  
Cord Injury

Background: Inflammation and mitochondrial dysfunction have been linked to trauma, neurodegeneration, and aging. Impairment of CISD2 expression may trigger the aforementioned pathological conditions in neural cells. We previously reported that curcumin attenuates the downregulation of CISD2 in animal models of spinal cord injury and lipopolysaccharide (LPS)-treated neuronal cells. In this study, we investigate (1) the role of CISD2 and (2) how curcumin regulates CISD2 in the aging process. Materials and methods: The serial expression of CISD2 and the efficacy of curcumin treatment were evaluated in old (104 weeks) mice and long-term cultures of neural cells (35 days in vitro, DIV). LPS-challenged neural cells (with or without siCISD2 transfection) were used to verify the role of curcumin on CISD2 underlying mitochondrial dysfunction. Results: In the brain and spinal cord of mice aged P2, 8, 25, and 104 weeks, we observed a significant decrease in CISD2 expression with age. Curcumin treatment in vivo and in vitro was shown to upregulate CISD2 expression; attenuate inflammatory response in neural cells. Moreover, curcumin treatment elevated CISD2 expression levels and prevented mitochondrial dysfunction in LPS-challenged neural cells. The beneficial effects of curcumin in either non-stressed or LPS-challenged cells that underwent siCISD2 transfection were significantly lower than in respective groups of cells that underwent scrambled siRNA-transfection. Conclusions: We hypothesize that the protective effects of curcumin treatment in reducing cellular inflammation associated trauma, degenerative, and aging processes can be partially attributed to elevated CISD2 expression. We observed a reduction in the protective effects of curcumin against injury-induced inflammation and mitochondrial dysfunction in cells where CISD2 expression was reduced by siCISD2.

scholarly journals Sodium Tanshinone IIA Silate Exerts Microcirculation Protective Effects against Spinal Cord Injury In Vitro and In Vivo

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Xing Li ◽  
Dan Luo ◽  
Yu Hou ◽  
Yonghui Hou ◽  
Shudong Chen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Endothelial Cells ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Tanshinone Iia ◽  
Protective Effects ◽  
Cord Injury

Spinal cord microcirculation involves functioning endothelial cells at the blood spinal cord barrier (BSCB) and maintains normal functioning of spinal cord neurons, axons, and glial cells. Protection of both the function and integrity of endothelial cells as well as the prevention of BSCB disruption may be a strong strategy for the treatment of spinal cord injury (SCI) cases. Sodium Tanshinone IIA silate (STS) is used for the treatment of coronary heart disease and improves microcirculation. Whether STS exhibits protective effects for SCI microcirculation is not yet clear. The purpose of this study is to investigate the protective effects of STS on oxygen-glucose deprivation- (OGD-) induced injury of spinal cord endothelial cells (SCMECs) in vitro and to explore effects on BSCB and neurovascular protection in vivo. SCMECs were treated with various concentrations of STS (1 μM, 3 μM, and 10 μM) for 24 h with or without OGD-induction. Cell viability, tube formation, migration, and expression of Notch signaling pathway components were evaluated. Histopathological evaluation (H&E), Nissl staining, BSCB permeability, and the expression levels of von Willebrand Factor (vWF), CD31, NeuN, and Notch signaling pathway components were analyzed. STS was found to improve SCMEC functions and reduce inflammatory mediators after OGD. STS also relieved histopathological damage, increased zonula occludens-1 (ZO-1), inhibited BSCB permeability, rescued microvessels, protected motor neuromas, and improved functional recovery in a SCI model. Moreover, we uncovered that the Notch signaling pathway plays an important role during these processes. These results indicated that STS protects microcirculation in SCI, which may be used as a therapeutic strategy for SCI in the future.

scholarly journals Melatonin protects spinal cord injury by up-regulating IGFBP3 through the improvement of microcirculation in a rat model

RSC Advances ◽  
2019 ◽  
Vol 9 (55) ◽  
pp. 32072-32080
Author(s):  
Kun Wang ◽  
Meng Li ◽  
Linyu Jin ◽  
Chao Deng ◽  
Zhi Chen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Cord Injury

The present study was aimed at the investigation of the effects of melatonin on spinal cord injury (SCI) and the role of IGFBP3 in SCI both in vivo and in vitro.

Circ-Ctnnb1 regulates neuronal injury in spinal cord injury through Wnt/β-catenin signaling pathway

2021 ◽  
Author(s):  
Jialong Qi ◽  
Tao Wang ◽  
Zhidong Zhang ◽  
Zongsheng Yin ◽  
Yiming Liu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signaling Pathway ◽  
Rat Model ◽  
Cell Model ◽  
Neuronal Cells ◽  
Neuronal Cell ◽  
Cord Injury

Study design: Spinal cord injury (SCI) rat model and cell model were established for in vivo and in vitro experiments. Functional assays were utilized to explore the role of the circRNAs derived from catenin beta 1 (mmu_circ_0001859, circ-Ctnnb1 herein) in regulating neuronal cell viability and apoptosis. Bioinformatics analysis and mechanism experiments were conducted to assess the underlying molecular mechanism of circ-Ctnnb1. Objective: We aimed to probe into the biological function of circ-Ctnnb1 in neuronal cells of SCI. Methods: The rat model of SCI and hypoxia-induced cell model were constructed to examine circ-Ctnnb1 expression in SCI through quantitative reverse transcription real-time polymerase chain reaction (RT-qPCR). Basso, Beattie and Bresnahan (BBB) score was utilized for evaluating the neurological function. Terminal-deoxynucleoitidyl Transferase Mediated Nick End labeling (TUNEL) assays were performed to assess the apoptosis of neuronal cells. RNase R and Actinomycin D (ActD) were used to treat cells to evaluate the stability of circ-Ctnnb1. Results: Circ-Ctnnb1 was highly expressed in SCI rat models and hypoxia-induced neuronal cells, and its deletion elevated the apoptosis rate of hypoxia-induced neuronal cells. Furthermore, circ-Ctnnb1 activated the Wnt/β-catenin signaling pathway via sponging mircoRNA-205-5p (miR-205-5p) to up-regulate Ctnnb1 and Wnt family member 2B (Wnt2b). Conclusion: Circ-Ctnnb1 promotes SCI through regulating Wnt/β-catenin signaling via modulating the miR-205-5p/Ctnnb1/Wnt2b axis.

scholarly journals Melatonin Alleviates Microglia-Mediated Neuroinflammation By Suppressing NLRP3 Inflammasome-Mediated Pyroptosis Via ROS/mtDNA/STING Pathway After Spinal Cord Injury

2021 ◽  
Author(s):  
Jin Wang ◽  
Haiyuan Yang ◽  
Fan Zhang ◽  
Minghao Shao ◽  
Haocheng Xu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Cord Injury ◽  
Sting Pathway

Abstract BackgroundMicroglia pyroptosis-induced neuroinflammation has been one of the potential treatment targets for spinal cord injury (SCI). And melatonin is reported to have anti-neuroinflammation effect on SCI, but the underlying mechanism is largely unexplored. In addition, the potential regulatory role of stimulator of interferon genes (STING) mediated innate immune response in the SCI-induced neuroinflammation also remains unknown. The aim of this study is to identify the potential molecular mechanism of the anti-neuroinflammation effect of melatonin in SCI mice and to explore whether STING-mediated signal pathway is involved in this pharmacological process. MethodsIn vivo, the C57BL/6 female mice underwent SCI injury or Sham surgery (laminectomy alone). Melatonin and selective STING antagonist C-176 were administered intraperitoneally after injury in the SCI group once a day for 3 or 28 consecutive days for different experiments. The BMS score system was adopted to assess the motor function of mice. In vitro, the Lipopolysaccharide (LPS)/ATP was combinedly used to induce cell pyroptosis in BV2 microglia and the adenovirus was used to overexpress STING. A series of molecular experiments including Western blot (WB), quantitative real-time polymerase chain reaction (RT-qPCR), enzyme linked immunosorbent assay (ELISA) and immunofluorescence (IF) were performed in vivo and in vitro. ResultsOur results showed that melatonin effectively suppressed NLRP3 inflammasome-induced pyroptosis and STING-mediated pathway after SCI. In addition, C-176 also alleviated the NLRP3 inflammasome-mediated pyroptosis and promoted functional recovery in vivo. In vitro, we also found that melatonin abrogated NLRP3 inflammasome activation in LPS/ATP-induced BV2 cells, while overexpression of STING reversed the anti-pyroptotic role of melatonin. Subsequent results together indicated that the role of melatonin on STING-dependent NLRP3 inflammasome activation may be mediated by decreasing ROS production and cytosolic mtDNA release. ConclusionThis study preliminarily demonstrated that melatonin exerts its anti-neuroinflammation role on SCI by alleviating the NLRP3 inflammasome-mediated pyroptosis, which was mediated by blocking the ROS/mtDNA/STING pathway. It provides us a better understanding of the pathological mechanism after SCI and offer experiment evidence to promote the use of melatonin for SCI.

scholarly journals MicroRNA-129-5p alleviates spinal cord injury in mice via suppressing the apoptosis and inflammatory response through HMGB1/TLR4/NF-κB pathway

2020 ◽  
Vol 40 (3) ◽  
Author(s):  
Guang Wan ◽  
Yongbo An ◽  
Jingang Tao ◽  
Yanli Wang ◽  
Qinglan Zhou ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Cell Model ◽  
Expression Profiles ◽  
Secondary Injury ◽  
High Mobility Group Protein ◽  
Cord Injury

Abstract Secondary injury after spinal cord injury (SCI) is one reversible pathological change mainly involving excessive inflammatory response and neuro-apoptosis. Since in recent years, microRNAs (miRNAs) have been proposed as novel regulators of inflammation in different disease conditions. However, the role of miRNAs in the inflammatory response and apoptosis of secondary injury after SCI remains to be fully elucidated. Here, we tried to explore the influence and mechanism of miRNAs on the neuron inflammatory response and apoptosis after SCI. The expression profiles of miRNA were examined using miRNA microarray, and among the candidate miRNAs, miR-129-5p was found to be the most down-regulated miRNA in spinal tissues. Overexpression of miR-129-5p using agomir-miR-129-5p promoted injury mice functional recovery, suppressed the apoptosis and alleviated inflammatory response in spinal tissues. Using LPS-induced BV-2 cell model, we found miR-129-5p was also proved in protecting inflammatory response and cell apoptosis in vitro. High-mobility group protein B1 (HMGB1), a well-known inflammatory mediator, was found to be directly targeted by miR-129-5p and it was associated with the inhibitory effect of miR-129-5p on the activation of toll-like receptor (TLR)-4 (TLR4)/ nuclear factor-κB (NF-κB) pathway in vitro and in vivo. Further experiments revealed that the anti-apoptosis and anti-inflammatory effects of miR-129-5p were reversed by HMGB1 overexpression in BV-2 cells. Collectively, these data revealed that miR-129-5p alleviated SCI in mice via suppressing the apoptosis and inflammatory response through HMGB1//TLR4/NF-κB pathway. Our data suggest that up-regulation of miR-129-5p may be a novel therapeutic target for SCI.

scholarly journals Knockdown of long non-coding RNA LEF1-AS1 attenuates apoptosis and inflammatory injury of microglia cells following spinal cord injury

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Sheng-Yu Cui ◽  
Wei Zhang ◽  
Zhi-Ming Cui ◽  
Hong Yi ◽  
Da-Wei Xu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Viability ◽  
Microglial Cells ◽  
Protective Effects ◽  
Loss Of Function ◽  
Sprague Dawley ◽  
Cord Injury ◽  
Apoptosis And Inflammation

Abstract Background Spinal cord injury (SCI) is associated with health burden both at personal and societal levels. Recent assessments on the role of lncRNAs in SCI regulation have matured. Therefore, to comprehensively explore the function of lncRNA LEF1-AS1 in SCI, there is an urgent need to understand its occurrence and development. Methods Using in vitro experiments, we used lipopolysaccharide (LPS) to treat and establish the SCI model primarily on microglial cells. Gain- and loss of function assays of LEF1-AS1 and miR-222-5p were conducted. Cell viability and apoptosis of microglial cells were assessed via CCK8 assay and flow cytometry, respectively. Adult Sprague-Dawley (SD) rats were randomly divided into four groups: Control, SCI, sh-NC, and sh-LEF-AS1 groups. ELISA test was used to determine the expression of TNF-α and IL-6, whereas the protein level of apoptotic-related markers (Bcl-2, Bax, and cleaved caspase-3) was assessed using Western blot technique. Results We revealed that LncRNA LEF1-AS1 was distinctly upregulated, whereas miR-222-5p was significantly downregulated in LPS-treated SCI and microglial cells. However, LEF1-AS1 knockdown enhanced cell viability, inhibited apoptosis, as well as inflammation of LPS-mediated microglial cells. On the contrary, miR-222-5p upregulation decreased cell viability, promoted apoptosis, and inflammation of microglial cells. Mechanistically, LEF1-AS1 served as a competitive endogenous RNA (ceRNA) by sponging miR-222-5p, targeting RAMP3. RAMP3 overexpression attenuated LEF1-AS1-mediated protective effects on LPS-mediated microglial cells from apoptosis and inflammation. Conclusion In summary, these findings ascertain that knockdown of LEF1-AS1 impedes SCI progression via the miR-222-5p/RAMP3 axis.

scholarly journals A Collagen-Based Scaffold for Promoting Neural Plasticity in a Rat Model of Spinal Cord Injury

Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2245
Author(s):  
Jue-Zong Yeh ◽  
Ding-Han Wang ◽  
Juin-Hong Cherng ◽  
Yi-Wen Wang ◽  
Gang-Yi Fan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Neural Plasticity ◽  
Collagen Scaffold ◽  
Glial Scar ◽  
Beneficial Effects ◽  
Cord Injury

In spinal cord injury (SCI) therapy, glial scarring formed by activated astrocytes is a primary problem that needs to be solved to enhance axonal regeneration. In this study, we developed and used a collagen scaffold for glial scar replacement to create an appropriate environment in an SCI rat model and determined whether neural plasticity can be manipulated using this approach. We used four experimental groups, as follows: SCI-collagen scaffold, SCI control, normal spinal cord-collagen scaffold, and normal control. The collagen scaffold showed excellent in vitro and in vivo biocompatibility. Immunofluorescence staining revealed increased expression of neurofilament and fibronectin and reduced expression of glial fibrillary acidic protein and anti-chondroitin sulfate in the collagen scaffold-treated SCI rats at 1 and 4 weeks post-implantation compared with that in untreated SCI control. This indicates that the collagen scaffold implantation promoted neuronal survival and axonal growth within the injured site and prevented glial scar formation by controlling astrocyte production for their normal functioning. Our study highlights the feasibility of using the collagen scaffold in SCI repair. The collagen scaffold was found to exert beneficial effects on neuronal activity and may help in manipulating synaptic plasticity, implying its great potential for clinical application in SCI.

scholarly journals PapRIV, a BV-2 microglial cell activating quorum sensing peptide

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yorick Janssens ◽  
Nathan Debunne ◽  
Anton De Spiegeleer ◽  
Evelien Wynendaele ◽  
Marta Planas ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Cell Model ◽  
Dependent Manner ◽  
Communication Signals ◽  
Gram Positive Bacteria ◽  
A Cell ◽  
Gastro Intestinal Tract

AbstractQuorum sensing peptides (QSPs) are bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced by Bacillus cereus species. PapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and reach the brain. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite still remained active. PapRIV is thus able to cross the gastro-intestinal tract and the blood–brain barrier and shows in vitro activating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction.

scholarly journals Immunosuppressants Affect Human Neural Stem Cells In Vitro but Not in an In Vivo Model of Spinal Cord Injury

2013 ◽  
Vol 2 (10) ◽  
pp. 731-744 ◽  
Author(s):  
Christopher J. Sontag ◽  
Hal X. Nguyen ◽  
Noriko Kamei ◽  
Nobuko Uchida ◽  
Aileen J. Anderson ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
In Vivo Model ◽  
Human Neural Stem Cells ◽  
Cord Injury

scholarly journals Depolarization and electrical stimulation enhance in vitro and in vivo sensory axon growth after spinal cord injury

2018 ◽  
Vol 300 ◽  
pp. 247-258 ◽  
Author(s):  
Ioana Goganau ◽  
Beatrice Sandner ◽  
Norbert Weidner ◽  
Karim Fouad ◽  
Armin Blesch
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Electrical Stimulation ◽  
Axon Growth ◽  
Sensory Axon ◽  
Cord Injury
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