Resveratrol on the Inflammatory Environment of Rat Bone Marrow Mesenchymal Cells

2021 ◽  
Vol 11 (10) ◽  
pp. 1932-1939
Author(s):  
Shaofeng Tang ◽  
Nvzhao Yao ◽  
Dahai Qin
Keyword(s):  
Spinal Cord ◽  
Sham Group ◽  
Inflammatory Factors ◽  
Sham Operation ◽  
Spinal Cord Tissue ◽  
Sham Operation Group ◽  
Western Blot Method ◽  
Cord Injury ◽  
Operation Group ◽  
Bone Marrow Mesenchymal Cells

Our study assesses the mechanism of Sirt-1 signaling pathway and inflammation changes after spinal cord injury (SCI). SD rats were assigned into Sham group and SCI group. The Sham group only received bites off the corresponding vertebral lamina without the blow operation. The Western Blot method was used to detect Sirt-1 level, ELISA analyzed IL-1β and IL-6 level in the spinal cord tissues along with measuring Sirt-1 and TNF-α level by immunofluorescence staining. Sirt-1 changed with the time after SCI and was significantly higher than sham operation group at 1 day after injury, reaching the highest level at 3 days followed by a decrease. IL-1β and IL-6 after SCI was significantly higher than sham operation group at 1 day after injury. Immunofluorescence double staining showed that Sirt-1 and TNF-α expression in spinal cord tissue after injury were upregulated. The expression of Sirt-1 changed with time after SCI, and was consistent with the trend of changes in inflammatory factors. In conclusion, Sirt-1 is related to the changes of inflammatory factors after SCI, indicating that Sirt-1 may be involved in inflammation after SCI.

scholarly journals The effect of lithium chloride on the motor function of spinal cord injury–controlled rat and the relevant mechanism

2019 ◽  
Vol 17 ◽  
pp. 205873921985285
Author(s):  
Gang Chen ◽  
Yimin Liang ◽  
Fanghu Chen ◽  
Haifeng Wang ◽  
Guoming Zhu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Lithium Chloride ◽  
Sham Operation ◽  
Model Group ◽  
Nissl Staining ◽  
Sham Operation Group ◽  
Significant Difference ◽  
Cord Injury ◽  
Operation Group

The objective of this study is to discuss the effect and mechanism of lithium chloride on the rehabilitation of locomotion post spinal cord injury (SCI) by observing the effect of lithium chloride on the expression of the brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) pathway. In total, 36 Sprague-Dawley (SD) rats were randomly divided into the sham operation group (n = 12), model group (n = 12), and lithium chloride group (n = 12). The sham operation group underwent laminectomy, while for the model group and the lithium chloride group with the NYU spinal cord impactor the SCI model was established. Basso, Beattie, and Bresnahan (BBB) score was used to evaluate locomotion after administration for 1, 3, 5, and 7 days, and the tissues were gathered for Nissl staining, transmission electron microscopy, immunofluorescence, and Western blot. With a statistical difference ( P < 0.05) on the 3rd day and significant difference ( P < 0.01) on the 5th day post administration, a higher BBB score was observed in the lithium chloride group indicating that lithium chloride improved the locomotion function after SCI. A better structure and morphology of neuron were observed by Nissl staining in the lithium chloride group. Lithium chloride promoted BDNF secretion from neurons in the spinal cord anterior horn with a significant difference compared to the model group ( P < 0.01). Compared with the model group, lithium chloride significantly promoted the expression of BDNF protein and phosphorylated TrkB protein ( P < 0.05), but no difference in the expression of TrkB was detected. Lithium chloride can alleviate the locomotion function after SCI with a mechanism that it can promote BDNF secretion from neurons in the spinal cord anterior horn and phosphorylation of TrkB to upregulate the BDNF/TrkB pathway supporting survival of neurons and regeneration and remyelination of axons.

scholarly journals Exendin-4 improves neuron protection and functional recovery in experimental spinal cord injury in rats through regulating PCBP2 expression

2020 ◽  
Author(s):  
Huaichao Luo ◽  
Qingwei Wang ◽  
Lei Wang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Apoptosis ◽  
Sham Group ◽  
Sham Operation ◽  
Therapeutic Effects ◽  
Rat Models ◽  
Apoptosis Rate ◽  
Cord Injury ◽  
Group A

AbstractAimsIn the present research, we assessed the therapeutic effects of Exendin-4 (Ex-4) on rat models with spinal cord injury (SCI).Materials and methods36 male Sprague–Dawley rats were randomly allocated into three groups, including sham operation group, SCI group and SCI+Ex-4 group (Ex-4 treatment (10 µg/rat) after SCI, i.p.). In the SCI group, a laminectomy was performed at the T10 vertebrae, followed by weight-drop contusion of the spinal cord. In the sham group, a laminectomy was carried out without SCI contusion.Key findingsOur results showed that Basso-Beattie-Bresnahan scale scores were significantly decreased after SCI, and were obviously improved in SCI rats with Ex-4 administration. Additionally, the water content of spinal cord in SCI group was dramatically increased than that in sham group, and after Ex-4 treatment, degree of edema of spinal cord was remarkably reduced. And also, concentration levels of inflammatory cytokines (IL-1α, IL-1β, IL-6 and TNF-α) in the spinal cord were significantly elevated after SCI, and were remarkably reduced in SCI rats with Ex-4 administration. Subsequently, cell apoptosis rate in the injured spinal cord was significantly increased, and after Ex-4 treatment, cell apoptosis rate was remarkably decreased. We also revealed that levels of PCBP2 mRNA and protein were significantly up-regulated after SCI, and were dramatically dropped in SCI rats with Ex-4 administration.SignificanceTake altogether, our findings disclosed that Ex-4 plays a role in promoting neurological function recovery and inhibiting neuronal apoptosis through effecting PCBP2 expression in SCI rat models.

scholarly journals Transcriptomic analysis of α-synuclein knockdown after T3 spinal cord injury in rats

2019 ◽  
Author(s):  
Hong Zeng ◽  
Bao-fu Yu ◽  
Nan Liu ◽  
Yan-yan Yang ◽  
Hua-yi Xing ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Lentiviral Vector ◽  
Cell Junction ◽  
Receptor Interaction ◽  
Sham Operation ◽  
Rna Seq ◽  
Sprague Dawley ◽  
Sham Operation Group ◽  
Cord Injury

Abstract Abstract Background Endogenous α-synuclein (α-Syn) is involved in many pathophysiological processes in the secondary injury stage after acute spinal cord injury (SCI), and the mechanism governing these functions has not been thoroughly elucidated to date. This research aims to characterize the effect of α-Syn knockdown on transcriptional levels after SCI and to determine the mechanisms underlying α-Syn activity based on RNA-seq. Result The establishment of a rat model of lentiviral vector-mediated knockdown of α-Syn in Sprague-Dawley rats with T3 spinal cord contusion. The results of the RNA-SEQ analysis showed that there were 191 differentially expressed genes (DEGs) between the SCI group and the LV_SCI group, and 96 DEGs in the LV_SCI group compared with the sham operation group (CON group). The top 20 biological transition terms were identified by Gene ontology (GO) analysis. The Kyoto Gene and Genomic Encyclopedia (KEGG) analysis showed that the LV_SCI group significantly up-regulated the cholinergic synaptic pathway and the neuroactive ligand receptor interaction signaling pathway. Enriched chord analysis analyzes key genes. Further cluster analysis, gene and protein interaction network analysis showed that Chrm2 and Chrnb2 together observed the LV_SCI group to promote the proliferation of Chrm2 and Chrnb2 and the neurogenesis of the injury site by immunofluorescence. Further by subcellular localization, the LV_SCI group enhanced the expression of Chrnb2 at the cell membrane and cell junction. Conclusion Knockdown of α-synuclein after spinal cord injury enhance motor function and promote neurogenesis probably through enhancing cholinergic signaling pathways and neuroreceptor interactions. This study not only further clarifies the understanding of the mechanism of knockdown of α-synuclein on SCI but also helps to guide the treatment strategy for 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.

scholarly journals Repairing and Analgesic Effects of Umbilical Cord Mesenchymal Stem Cell Transplantation in Mice with Spinal Cord Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ling-ling Wu ◽  
Xiao-ming Pan ◽  
Hao-hao Chen ◽  
Xiao-yan Fu ◽  
Jinzhan Jiang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Treatment Group ◽  
Pain Threshold ◽  
Inflammatory Factors ◽  
Histological Evaluation ◽  
Spinal Cord Tissue ◽  
Model Group ◽  
Analgesic Effects ◽  
Cord Injury ◽  
Over Time

Transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) into spinal cord injury (SCI) may alleviate neuropathic pain and promote functional recovery. The underlying mechanism likely involves activation of glial cells and regulation of inflammatory factors but requires further validation. SCI was induced in 16 ICR mice using an SCI compression model, followed by injection of lentiviral vector-mediated green fluorescent protein- (GFP-) labeled hUC-MSCs 1 week later. Behavioral tests, histological evaluation, and inflammatory factor detection were performed in the treatment (SCI+hUC-MSCs) and model (SCI) groups. Histological evaluation revealed GFP expression in the spinal cord tissue of the treatment group, implying that the injected MSCs successfully migrated to the SCI. The Basso, Beattie, and Bresnahan (BBB) scores showed that motor function gradually recovered over time in both groups, but recovery speed was significantly higher in the treatment group than in the model group. The pain threshold in mice decreased after SCI but gradually increased over time owing to the self-repair function of the body. The corresponding pain threshold of the treatment group was significantly higher than that of the model group, indicating the therapeutic and analgesic effects of hUC-MSCs. Expression of IL-6 and TNF-α in the spinal cord tissue of the treated group decreased, whereas glial cell line-derived neurotrophic factor (GDNF) expression along with ED1 expression increased compared with those in the model group, suggesting that SCI activated ED1 inflammatory macrophages/microglia, which were subsequently reduced by hUC-MSC transplantation. hUC-MSCs are speculated to enhance the repair of the injured spinal cord tissue and exert an analgesic effect by reducing the secretion of inflammatory factors IL-6 and TNF-α and upregulating the expression of GDNF.

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 MiR-139-5p alleviates neural cell apoptosis induced by spinal cord injury through targeting TRAF3

2020 ◽  
Author(s):  
Ziying Zhang ◽  
Lifang Shen ◽  
Yingying Yan
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Cell Apoptosis ◽  
Target Genes ◽  
Neural Cell ◽  
Sham Operation ◽  
Sham Operation Group ◽  
Cord Injury

Spinal cord injury (SCI) is a neurological trauma that causes loss of locomotor function and sensory deficit. Previous studies showed that miRNAs play a crucial role in SCI. This study further evaluated the potential role of miR-139-5p in the neural cell apoptosis after SCI in rats. A rat SCI model was successfully established and miR-139-5p expression level in SCI rats was down-regulated compared to the sham group (sham operation group) determined by qRT-PCR. MiR-139-5p overexpression via administration with miR-139-5p agomir improved locomotor functional recovery, attenuated allodynia and hyperalgesia and alleviated neural cell apoptosis in SCI rats. In addition, TRAF3 (TNF receptor-associated factor 3 ) was identified to be a target of miR-139-5p by searching the proposed target genes in TargetScan 7.1 database. Co-transfection of miR-139-5p agomir and adenovirus of TRAF3 plasmids significantly improved functional recovery and alleviated neural cell apoptosis. Therefore, TRAF3 mediated the anti-apoptosis effect of miR-139-5p in SCI rats and miR-139-5p could be a promising candidate for SCI therapy by alleviating neural cell apoptosis through targeting TRAF3.

A long-term survival rat model of spinal cord ischemia injury: Thoracic aortic occlusion combined with aortic bypass circulation

Vascular ◽  
2021 ◽  
pp. 170853812110601
Author(s):  
Cheng-yong Yin ◽  
Jun-jie Fei ◽  
Yu-yin Duan ◽  
Ke Yang ◽  
Xin Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Treatment Group ◽  
Thoracic Aorta ◽  
Aortic Occlusion ◽  
Control Group ◽  
Sham Operation ◽  
Term Survival ◽  
Sham Operation Group ◽  
Aortic Bypass ◽  
Operation Group

Objective This study aims to investigate the methods for rat spinal cord ischemia injury models with a high long-term survival rate. Methods The rats were divided into three groups: the treatment group, the control group, and the sham operation group. The treatment group had a blocked thoracic aorta (landing zone 3 by Ishimaru – T11) + aortic bypass circulation for 20 min. In the control group, the thoracic aorta at the landing zone 3 was blocked for 20 min. In the sham operation group, only thoracotomy without thoracic aortic occlusion was performed. The mean arterial blood pressure (MABP) of the thoracic aorta and caudal artery before and after thoracic aortic occlusion was monitored intraoperatively. Spinal cord function was monitored by a transcranial motor evoked potential (Tc-MEP) during the operation. Spinal cord function was evaluated by the BBB scale (Basso, Beattie, & Bresnahan locomotor rating scale) scores at multiple postoperative time points. The spinal cord sections of the rats were observed for 7 days after surgery, and the survival curves were analyzed for 28 days after surgery. Results After aortic occlusion, the MABP of thoracic aorta decreased to 6% of that before occlusion, and the MABP of caudal artery decreased to 63% of that before occlusion in the treatment group. In the control group, the MABP of both thoracic aorta and caudal artery decreased to 19% of that before occlusion. The Tc-MEP waveform of the treatment group disappeared after 6 min, and that of the control group disappeared after 8 min until the end of surgery. There was no change in the Tc-MEP waveform in the sham operation group. The BBB score of the treatment group decreased more obviously than the control group, and there was a significant difference. There was no decrease in the sham group. Spinal cord sections showed a large number of degeneration and necrosis of neurons, infiltration of inflammatory cells, and proliferation of surrounding glial cells in the treatment group. In the control group, multiple neurons were necrotic. The histology of the sham operation group was normal. The 28-day survival rate of the treatment group was 73.3%, which was higher than the control group (40.0%), and there was a significant difference ( p < 0.05). Conclusion Thoracic aortic occlusion combined with aortic bypass is an effective modeling method for rats with accurate modeling effects and high long-term survival rates.

scholarly journals Expression of Slit and Robo During Remodeling of Corticospinal Tract in Cervical Spinal Cord in Middle Cerebral Artery Occlusion Rats

2021 ◽  
Author(s):  
Zhenhao Ying ◽  
Junxuan Wu ◽  
Wenjun Jiang ◽  
Guoli Zhang ◽  
Weiming Zhu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Function ◽  
Corticospinal Tract ◽  
Cervical Spinal Cord ◽  
Artery Occlusion ◽  
Sham Operation ◽  
Model Group ◽  
Sham Operation Group ◽  
Operation Group ◽  
Cerebral Artery Occlusion

Abstract Background: Slits and Robos were associated with the generation of axons of corticospinal tract during the corticospinal tract (CST) remodeling after the cerebral ischemic stroke (CIS). However, little is known about the mechanism of CST remodeling. In this study, we detected the expression of Slits and Robos in middle cerebral artery occlusion (MCAO) rats to investigate the roles of Slits and Robos in the CIS. Methods: MCAO model was established using modified Zea Longa method. Beam walking test (BWT) was conducted to evaluate the motor function. The images of the track of cortical spinal cord beam on day 7, 14 and 21 were observed by anterograde CST tracing. Biopinylated dextan amine (BDA) was used to mark CST anterogradely. Expression of GAP-43 mRNA and GAP-43 protein in cervical spinal cord was detected by Real-Time PCR and Western blot analysis, respectively. The expression of Slit1, Slit2 and Robo1 in cervical spinal cord was detected by immunofluorescence staining.Results: The scores in the model group were significantly reduced compared to sham-operation group on day 7 (P<0.001), 14 (P<0.001) and 21 (P<0.001), respectively. There was no significant difference in the score on day 7, 14 and 21 of the sham-operation groups (P>0.05). In contrast, significant increase was noticed in the scores in model group, presenting a time-dependent manner. More CST staining fibers could be observed at the degenerative side in the model group compared with that of the sham-operation group on day 21. GAP-43 mRNA expression in the model group showed significant increase compared to that of sham-operation group on day 14 (P=0.015) and 21 days (P=0.002). The expression of GAP-43 protein in model group showed significant increase compared to that of sham-operation group on day 14 (P=0.022) and day 21 (P=0.008), respectively. The expression of Slit1 and Slit2 showed increase on day 14 and day 21, while the expression of Robo1 showed significant decrease in MCAO rats.Conclusion: Up-regulation of Slit1 and Slit2 and the downregulation of Robo1 may be related to the axons of CST midline crossing in spinal cord of MCAO rat during the spontaneous recovery of impaired motor function.

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.

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