Autophagy induced by Schwann cell-derived exosomes promotes recovery after spinal cord injury in rats

AbstractSpinal cord injury (SCI) is catastrophic to humans and society. However, there is currently no effective treatment for SCI. Autophagy is known to serve critical roles in both the physiological and pathological processes of the body, but its facilitatory and/or deleterious effects in SCI are yet to be completely elucidated. This study aimed to use primary Schwann cell-derived exosomes (SCDEs) to treat rats after SCI. In the present study, SCDEs were purified and their efficacy in ameliorating the components of SCI was examined. Using both in vivo and in vitro experiments, it was demonstrated that SCDEs increased autophagy and decreased apoptosis after SCI, which promoted axonal protection and the recovery of motor function. Furthermore, it was discovered that an increased number of SCDEs resulted in a decreased expression level of EGFR, which subsequently inhibited the Akt/mTOR signaling pathway, which upregulated the level of autophagy to ultimately induce microtubule acetylation and polymerization. Collectively, the present study identified that SCDEs could induce axonal protection after SCI by increasing autophagy and decreasing apoptosis, and it was suggested that this may involve the EGFR/Akt/mTOR signaling pathway.

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In vivo and in vitro models of traumatic injuries of the spinal cord

Cell and Organ Transplantology ◽

10.22494/cot.v5i1.71 ◽

2017 ◽

Vol 5 (1) ◽

pp. 87-93

Author(s):

O. Rybachuk ◽

I. Arkhypchuk ◽

Yu. Lazarenko

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Traffic Accidents ◽

Experimental Models ◽

The Body ◽

Nerve Tissue ◽

Economic Losses ◽

Cord Injury

In recent years, there is a growing interest in the mechanisms of regeneration of damaged nerve tissue, including the spinal cord, as its injuries are quite common due to traffic accidents, industrial injuries and military actions. Damage to the spinal cord results in the loss of functional activity of the body below the injury site, which affects person’s ability to self-service and significantly reduces its efficiency. The effects of spinal injuries annually cause significant social and economic losses worldwide, including Ukraine. The development of new treatments for pathologies of the central nervous system requires mandatory pre-testing of their effectiveness in experiments in vitro and in vivo. Therefore, searching and creation of optimal animal model of spinal cord injury is in order to it meets most complete picture of the damage characteristic of real conditions in humans. This is an important task of modern neurophysiology. Such models can be used, primarily, for a more detailed clarification of the pathogenesis of all levels of nerve tissue damage and research of its own recovery potential by endogenous reparation mechanisms. In addition, experimental models allow to estimate the safety and predict the effectiveness of various therapeutic approaches to spinal cord injury.

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

Developmental Neuroscience ◽

10.1159/000521172 ◽

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.

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Beneficial Effects of Resveratrol-Mediated Inhibition of the mTOR Pathway in Spinal Cord Injury

Neural Plasticity ◽

10.1155/2018/7513748 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Jingying Zhou ◽

Xue Huo ◽

Benson O. A. Botchway ◽

Luyao Xu ◽

Xiaofang Meng ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Signaling Pathway ◽

Mammalian Target Of Rapamycin ◽

Mtor Pathway ◽

Mtor Signaling ◽

High Rate ◽

Mtor Signaling Pathway ◽

Beneficial Effects ◽

Cord Injury

Spinal cord injury (SCI) causes a high rate of morbidity and disability. The clinical features of SCI are divided into acute, subacute, and chronic phases according to its pathophysiological events. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in cell death and inflammation in the acute phase and neuroregeneration in the subacute/chronic phases at different times. Resveratrol has the potential of regulating cell growth, proliferation, metabolism, and angiogenesis through the mTOR signaling pathway. Herein, we explicate the role of resveratrol in the repair of SCI through the inhibition of the mTOR signaling pathway. The inhibition of the mTOR pathway by resveratrol has the potential of serving as a neuronal restorative mechanism following SCI.

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Gal-3 is a potential biomarker for spinal cord injury and Gal-3 deficiency attenuates neuroinflammation through ROS/TXNIP/NLRP3 signaling pathway

Bioscience Reports ◽

10.1042/bsr20192368 ◽

2019 ◽

Vol 39 (12) ◽

Cited By ~ 6

Author(s):

Zhouliang Ren ◽

Weidong Liang ◽

Jun Sheng ◽

Chuanhui Xun ◽

Tao Xu ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Signaling Pathway ◽

In Vitro Model ◽

Sd Rat ◽

Potential Biomarker ◽

Cord Injury ◽

Vitro Model

Abstract Spinal cord injury (SCI) often occurs in young and middle-aged population. The present study aimed to clarify the function of Galectin-3 (Gal-3) in neuroinflammation of SCI. Sprague–Dawley (SD) rat models with SCI were established in vivo. PC12 cell model in vitro was induced by lipopolysaccharide (LPS). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Gene chip were used to analyze the expression levels of genes in the signaling pathway. Histological assessment, ELISA and Western blotting were conducted to evaluate the effects of Gal-3 upon the SCI model. In the in vivo SD rat model, Gal-3 expression level was up-regulated. The inhibition of Gal-3 attenuated the neuroinflammation in SCI model. The inhibition of Gal-3 could also mitigate the neuroinflammation and reactive oxygen species (ROS) in in vitro model. ROS reduced the effect of Gal-3 on oxidative stress in in vitro model. Down-regulating the content of TXNIP decreased the effect of Gal-3 on neuroinflammation in in vitro model. Suppressing the level of NLRP3 could weaken the effect of Gal-3 on neuroinflammation in in vitro model. Our data highlight that the Gal-3 plays a vital role in regulating the severity of neuroinflammation of SCI by enhancing the activation of ROS/TXNIP/NLRP3 signaling pathway. In addition, inflammasome/IL-1β production probably acts as the therapeutic target in SCI.

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

Neural Plasticity ◽

10.1155/2020/5474608 ◽

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.

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