scholarly journals Effects of MicroRNA-494 on Astrocyte Proliferation and Synaptic Remodeling in the Spinal Cord of a Rat Model of Chronic Compressive Spinal Cord Injury by Regulating the Nogo/Ngr Signaling Pathway

2018 ◽  
Vol 48 (3) ◽  
pp. 919-933 ◽  
Author(s):  
Yuan Wang ◽  
Jing-Chuan Sun ◽  
Hai-Bo Wang ◽  
Xi-Ming Xu ◽  
Yong Yang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signaling Pathway ◽  
Motor Neurons ◽  
Rat Model ◽  
Target Genes ◽  
Quantitative Polymerase Chain Reaction ◽  
Astrocyte Proliferation ◽  
Synaptic Remodeling ◽  
Cord Injury

Background/Aims: Chronic compression of the spinal cord causes the loss of motor neurons in the anterior horn, but the precise and extensive mechanism for the loss is not completely determined. Therefore, this study aims to explore the role of microRNA-494 (miR-494) in the proliferation of astrocytes and in the synaptic remodeling in the spinal cord of a rat model of chronic spinal cord injury (SCI) by regulating the Nogo/NgR signaling pathway. Methods: A rat model of chronic, compressive SCI was established, and the spinal cord state, blood supply changes, and astrocyte apoptosis were observed. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to detect expression of miR-494 and the Nogo/NgR signaling pathway-related genes. Fluorescence in situ hybridization (FISH) was used for detecting miR-494 expression and distribution. Results: Higher miR-494 expression was accompanied by the inhibition of astrocyte proliferation and synaptic remodeling. In addition, CDK6 could be regulated by miR-494 and was shown to be one of the target genes of miR-494. Positive expression of miR-494 detected by FISH was consistent with the results from RT-qPCR that miR-494 could downregulate CDK6 gene expression. Moreover, the direct miR-494 target CDK6 plays important inhibitory roles in chronic SCI by suppressing the Nogo/ NgR signaling pathway. Conclusions: The results demonstrated that miR-494 inhibition can promote astrocyte proliferation and synaptic remodeling by suppressing the Nogo/NgR signaling pathway in a rat model of chronic SCI.

scholarly journals MicroRNA-146a Contributes to SCI Recovery via Regulating TRAF6 and IRAK1 Expression

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Jinsong Wei ◽  
Jiafeng Wang ◽  
Yulan Zhou ◽  
Shouquan Yan ◽  
Keshen Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Proinflammatory Cytokine ◽  
Target Genes ◽  
Sham Group ◽  
Luciferase Assay ◽  
Tight Control ◽  
Cord Injury ◽  
Novel Therapeutic

MicroRNA-146a participates in spinal cord injury (SCI) recovery. Until recently, how miRNA-146a participates in SCI remained unclear. In this study, we tried to explore the roles of miRNA-146a in the recovery of SCI using a rat model. The expression of the probable target genes of miRNA-146a (including IRAK1 and TARF6) as well as proinflammation cytokines were measured until 7 days after surgery in the three groups (sham group, SCI group, and miRNA-146a antagomir injection group). Also, the animals’ motivations were estimated using Basso Beattie Bresnahan (BBB) during the whole experiment. A luciferase assay was performed to demonstrate that miRNA-146a could directly target the mRNAs of IRAK1 and TRAF6. Our experiments indicate that miRNA-146a inhibits proinflammatory cytokine secretion by suppressing IRAK1 and TRAF6 expression in the SCI model. In contrast, miRNA-146a may be upregulated by inflammatory mediators via the IRAK1/TRAF6 pathway in the spinal cord. As a negative feedback element, miRNA-146a could make sure that the expression of IRAK1- and TRAF6-mediated genes was under tight control. Thus, miRNA-146a may serve as a novel therapeutic target for SCI interventions.

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 Up-regulation of MicroRNAs-21 and -223 in a Sprague-Dawley Rat Model of Traumatic Spinal Cord Injury

2020 ◽  
Vol 10 (3) ◽  
pp. 141
Author(s):  
Hyo-Jin Chung ◽  
Wook-Hun Chung ◽  
Sun-Hee Do ◽  
Jae-Hoon Lee ◽  
Hwi-yool Kim
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Rating Scale ◽  
Quantitative Polymerase Chain Reaction ◽  
Balloon Catheter ◽  
Traumatic Spinal Cord Injury ◽  
Sprague Dawley ◽  
Time Points ◽  
Cord Injury

In this experimental animal study, we examined alterations in the degree of transcription of two microRNAs (miRs)—miR-21 and -223—in a Sprague-Dawley (SD) rat model of traumatic spinal cord injury (TSCI). Depending on the volume of the balloon catheter (V), a total of 75 male SD rats were divided into the three experimental groups: the sham group (n = 25; V = 0 μL), the mild group (n = 25; V = 20 μL), and the severe group (n = 25; V = 50 μL). Successful induction of TSCI was confirmed on both locomotor rating scale at 4 h and 1, 3 and 7 days post-lesion and histopathologic examinations. Then, RNA isolation and quantitative polymerase chain reaction (PCR) were performed. No differences in the level of miR-21 expression were found at the first time point studied (4 h post-lesion) between the three experimental groups, whereas such differences were significant at all the other time points (p < 0.05). Moreover, there were significant alterations in the level of miR-223 expression at all time points studied through all the experimental groups (p < 0.05). Furthermore, locomotor rating scale scores had a linear relationship with the level of miR-21 expression (R2 = 0.4363, Y = 1.661X + 3.096) and that of miR-223 one (R2 = 0.9104, Y = 0.8385X + 2.328). Taken together, we conclude that up-regulation of miR-21 and -223 might be closely associated with progression and the early course of TSCI, respectively.

scholarly journals Implication of cholinergic transmission in rat model of spinal cord injury: A potential therapeutic target

2021 ◽  
Vol 18 (4) ◽  
pp. 741-745
Author(s):  
Hongzhe Liu ◽  
Lei Chang ◽  
Shuai Peng ◽  
Bin Liu ◽  
Mingyan Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Quantitative Polymerase Chain Reaction ◽  
Motor Deficits ◽  
Cholinergic Transmission ◽  
Binding Studies ◽  
Adult Rats ◽  
Male Adult ◽  
Cord Injury

Purpose: To assess the involvement of cholinergic transmission in the etiology of spinal cord injury (SCI) in a rat model. Methods: Male adult rats (Wistar) with body weight ranging from 200 to 250 g were equally allocated into 2 groups: test (SCI) and control (non-SCI). Clipping method was used to induce SCI. Thereafter, motor function was measured using rotarod. Each rat was sacrificed by decapitation, and the cortex was excised for use in the study of the involvement of cholinergic transmission in SCI using real time quantitative polymerase chain reaction (RT-PCR) and western blot analysis (WBA). Results: Significant upregulation in acetylcholine esterase (AChE) was observed in the cortex of SCI rats, relative to non-SCI rats (p < 0.005). Results from cholinergic receptor binding studies revealed significantly decreased maximum binding (Bmax) and dissociation constant (kd) values for muscarinic receptors in SCI rats, when compared to non-SCI rats. Moreover, the reduction in intensity of cholinergic receptors was significantly greater in the cerebral cortex of SCI group compared to non-SCI group. Conclusion: The results of this study suggested that the reduction in cortical cholinergic transmission impairs motor functions in SCI, and plays a major role in motor deficits in SCI.

scholarly journals Restoration of breathing after opioid overdose and spinal cord injury using temporal interference stimulation

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Michael D. Sunshine ◽  
Antonino M. Cassarà ◽  
Esra Neufeld ◽  
Nir Grossman ◽  
Thomas H. Mareci ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Neurons ◽  
Drug Overdose ◽  
Cervical Spinal Cord ◽  
Opioid Overdose ◽  
Electrode Position ◽  
Spinal Motor Neurons ◽  
Cord Injury ◽  
Low Amplitude

AbstractRespiratory insufficiency is a leading cause of death due to drug overdose or neuromuscular disease. We hypothesized that a stimulation paradigm using temporal interference (TI) could restore breathing in such conditions. Following opioid overdose in rats, two high frequency (5000 Hz and 5001 Hz), low amplitude waveforms delivered via intramuscular wires in the neck immediately activated the diaphragm and restored ventilation in phase with waveform offset (1 Hz or 60 breaths/min). Following cervical spinal cord injury (SCI), TI stimulation via dorsally placed epidural electrodes uni- or bilaterally activated the diaphragm depending on current and electrode position. In silico modeling indicated that an interferential signal in the ventral spinal cord predicted the evoked response (left versus right diaphragm) and current-ratio-based steering. We conclude that TI stimulation can activate spinal motor neurons after SCI and prevent fatal apnea during drug overdose by restoring ventilation with minimally invasive electrodes.

scholarly journals CD157 in bone marrow mesenchymal stem cells mediates mitochondrial production and transfer to improve neuronal apoptosis and functional recovery after spinal cord injury

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Li ◽  
Heyangzi Li ◽  
Simin Cai ◽  
Shi Bai ◽  
Huabo Cai ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Motor Neurons ◽  
Functional Recovery ◽  
Mitochondrial Transfer ◽  
Cord Injury ◽  
Marrow Mesenchymal Stem Cells

Abstract Background Recent studies demonstrated that autologous mitochondria derived from bone marrow mesenchymal stem cells (BMSCs) might be valuable in the treatment of spinal cord injury (SCI). However, the mechanisms of mitochondrial transfer from BMSCs to injured neurons are not fully understood. Methods We modified BMSCs by CD157, a cell surface molecule as a potential regulator mitochondria transfer, then transplanted to SCI rats and co-cultured with OGD injured VSC4.1 motor neuron. We detected extracellular mitochondrial particles derived from BMSCs by transmission electron microscope and measured the CD157/cyclic ADP-ribose signaling pathway-related protein expression by immunohistochemistry and Western blotting assay. The CD157 ADPR-cyclase activity and Fluo-4 AM was used to detect the Ca2+ signal. All data were expressed as mean ± SEM. Statistical analysis was analyzed by GraphPad Prism 6 software. Unpaired t-test was used for the analysis of two groups. Multiple comparisons were evaluated by one-way ANOVA or two-way ANOVA. Results CD157 on BMSCs was upregulated when co-cultured with injured VSC4.1 motor neurons. Upregulation of CD157 on BMSCs could raise the transfer extracellular mitochondria particles to VSC4.1 motor neurons, gradually regenerate the axon of VSC4.1 motor neuron and reduce the cell apoptosis. Transplantation of CD157-modified BMSCs at the injured sites could significantly improve the functional recovery, axon regeneration, and neuron apoptosis in SCI rats. The level of Ca2+ in CD157-modified BMSCs dramatically increased when objected to high concentration cADPR, ATP content, and MMP of BMSCs also increased. Conclusion The present results suggested that CD157 can regulate the production and transfer of BMSC-derived extracellular mitochondrial particles, enriching the mechanism of the extracellular mitochondrial transfer in BMSCs transplantation and providing a novel strategy to improve the stem cell treatment on SCI.

scholarly journals Multi-pronged neuromodulation intervention engages the residual motor circuitry to facilitate walking in a rat model of spinal cord injury

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marco Bonizzato ◽  
Nicholas D. James ◽  
Galyna Pidpruzhnykova ◽  
Natalia Pavlova ◽  
Polina Shkorbatova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Stress Responses ◽  
Learning Algorithm ◽  
Lumbar Spinal Cord ◽  
Cord Injury ◽  
Potential Synergy ◽  
Lumbar Spinal ◽  
Deep Brain

AbstractA spinal cord injury usually spares some components of the locomotor circuitry. Deep brain stimulation (DBS) of the midbrain locomotor region and epidural electrical stimulation of the lumbar spinal cord (EES) are being used to tap into this spared circuitry to enable locomotion in humans with spinal cord injury. While appealing, the potential synergy between DBS and EES remains unknown. Here, we report the synergistic facilitation of locomotion when DBS is combined with EES in a rat model of severe contusion spinal cord injury leading to leg paralysis. However, this synergy requires high amplitudes of DBS, which triggers forced locomotion associated with stress responses. To suppress these undesired responses, we link DBS to the intention to walk, decoded from cortical activity using a robust, rapidly calibrated unsupervised learning algorithm. This contingency amplifies the supraspinal descending command while empowering the rats into volitional walking. However, the resulting improvements may not outweigh the complex technological framework necessary to establish viable therapeutic conditions.

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