scholarly journals The GDF11 Promotes Nerve Regeneration After Sciatic Nerve Injury in Adult Rats by Promoting Axon Growth and Inhibiting Neuronal Apoptosis

2022 ◽  
Vol 9 ◽  
Author(s):  
Junhao Lin ◽  
Jie Shi ◽  
Xiang Min ◽  
Si Chen ◽  
Yunpeng Zhao ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Injury ◽  
Cell Apoptosis ◽  
Neuronal Apoptosis ◽  
Axonal Growth ◽  
Sciatic Nerve Injury ◽  
Smad Pathway ◽  
Sciatic Nerves

Introduction: Sciatic nerve injury is a common injury of the nervous system. Stem cell-based therapies, drug-based therapies and rehabilitation physiotherapy therapies are currently available, but their limited therapeutic efficacy limits their use. Here, we aimed to explore a novel lentiviral-based gene therapeutic strategy and to elaborate its mechanism.Materials and Methods: Recombinant GDF11 protein was used for the in vitro treatment of dorsal root ganglion (DRG) cells. Lentivirus was used to construct a vector system for the in vivo expression of GDF11. The nerve conduction function was detected using action-evoked potentials at different time periods, and the regulatory effect of nerves on target organs was detected by weighing the gastrocnemius muscle. Immunofluorescence of NF200 and S100 was used to show the regeneration of the sciatic nerve, and myelin and Nissl staining were performed to observe the pathological features of the tissue. Western was used to validate signaling pathways. The expression of related genes was observed by qPCR and Western blotting, and cell apoptosis was detected by flow cytometry.Result: GDF11 promotes the axonal growth of DRG cells and inhibits DGR cell apoptosis in vitro. GDF11 acts by activating the Smad pathway. GDF11 promotes the recovery of damaged sciatic nerve function in rats, the regeneration of damaged sciatic nerves in rats, and myelin regeneration of damaged sciatic nerves in rats. GDF11 also exerts a protective effect on neuronal cells in rats.Conclusion: Based on the present study, we conclude that GDF11 promotes axonal growth and inhibits DRG cell apoptosis in vitro through the Smad pathway, and lentivirus-mediated GDF11 overexpression in vivo can promote the recovery of sciatic nerves after transection by promoting axonal growth and inhibiting neuronal apoptosis in the spinal cord.

scholarly journals Recovery from rat sciatic nerve injury in vivo through the use of differentiated MDSCs in vitro

2012 ◽  
Vol 5 (1) ◽  
pp. 193-196 ◽  
Author(s):  
XIANGYI ZENG ◽  
LI ZHANG ◽  
LIANG SUN ◽  
DAI ZHANG ◽  
HENGWU ZHAO ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Injury ◽  
Sciatic Nerve Injury ◽  
Rat Sciatic Nerve

scholarly journals miRNA-155 silencing reduces sciatic nerve injury in diabetic peripheral neuropathy

2019 ◽  
Vol 63 (3) ◽  
pp. 227-238 ◽  
Author(s):  
Ji Chen ◽  
Chao Li ◽  
Wenjie Liu ◽  
Bin Yan ◽  
Xiaoling Hu ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
Diabetic Peripheral Neuropathy ◽  
Sciatic Nerve Injury ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Gene Assay

Neuropathic pain represents one of the most common complications associated with diabetes mellitus (DM) that impacts quality of life. Accumulating studies have highlighted the involvement of miRNAs in DM. Thus, the current study aimed to investigate the roles of miR-155 in diabetic peripheral neuropathy (DPN). In vitro DPN models were established using rat Schwann cells (SCs) by treatment with 5.5 mM glucose. Gain- or loss-of-function studies were conducted to determine the effect of miR-155 on Nrf2, cellular function, reactive oxygen species and inflammation. Rat DNP models were established by streptozotocin injection and damage of sciatic nerve. Next, miR-155 antagomir or agomir was employed to investigate the effects associated with miR-155 on motor and sciatic nerve conduction velocity (MNCV, SNCV), angiogenesis and inflammatory response in vivo. Nrf2 was identified to be a target of miR-155 by dual-luciferase reporter gene assay. Silencing of miR-155 or restoration of Nrf2 promoted cell proliferation, inhibited apoptosis and alleviated inflammation in vitro. miR-155 antagomir-induced inhibition increased MNCV and SNCV, strengthened angiogenesis and alleviated inflammation in DPN rats. Additionally, the effects exerted by miR-155 were reversed when Nrf2 was restored both in vitro and in vivo. Taken together, the key findings of our study provide evidence indicating that miR-155 targeted and suppressed Nrf2 in DPN. miR-155 silencing was found to alleviate sciatic nerve injury in DPN, highlighting its potential as a therapeutic target for DPN.

scholarly journals 3D-printed nerve guidance conduits multi-functionalized with canine multipotent mesenchymal stromal cells promote neuroregeneration after sciatic nerve injury in rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Diego Noé Rodríguez-Sánchez ◽  
Giovana Boff Araujo Pinto ◽  
Luciana Politti Cartarozzi ◽  
Alexandre Leite Rodrigues de Oliveira ◽  
Ana Livia Carvalho Bovolato ◽  
...  
Keyword(s):  
Growth Factor ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Sciatic Nerve Injury ◽  
Motor Deficits ◽  
3D Printed

Abstract Background Nerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth are supported and enhanced by growth factor and cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for nerve regeneration. Methods 3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected to critical sciatic nerve damage (12-mm gap) were divided into sham, autograft, PCL (empty NGC), and PCL + MSCs (NGC multi-functionalized with 106 canine AdMSCs embedded in heterologous fibrin biopolymer) groups. In vitro, the cells were characterized and directly stimulated with interferon-gamma to evaluate their neuroregeneration potential. In vivo, the sciatic and tibial functional indices were evaluated for 12 weeks. Gait analysis and nerve conduction velocity were analyzed after 8 and 12 weeks. Morphometric analysis was performed after 8 and 12 weeks following lesion development. Real-time PCR was performed to evaluate the neurotrophic factors BDNF, GDNF, and HGF, and the cytokine and IL-10. Immunohistochemical analysis for the p75NTR neurotrophic receptor, S100, and neurofilament was performed with the sciatic nerve. Results The inflammatory environment in vitro have increased the expression of neurotrophins BDNF, GDNF, HGF, and IL-10 in canine AdMSCs. Nerve guidance conduits multi-functionalized with canine AdMSCs embedded in HFB improved functional motor and electrophysiological recovery compared with PCL group after 12 weeks. However, the results were not significantly different than those obtained using autografts. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. Increased immunostaining of BDNF, GDNF, and growth factor receptor p75NTR was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL + MSCs group. A trend demonstrating higher reactivity of Schwann cells and axonal branching in the sciatic nerve was observed, and canine AdMSCs were engrafted at 30 days following repair. Conclusions 3D-printed NGCs multi-functionalized with canine AdMSCs embedded in heterologous fibrin biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach supports the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats.

Continuation of fast axonal transport in regenerating axons in vitro

1979 ◽  
Vol 57 (11) ◽  
pp. 1251-1255
Author(s):  
M. A. Bisby ◽  
C. E. Hilton
Keyword(s):  
Sciatic Nerve ◽  
Vagus Nerve ◽  
Axonal Transport ◽  
Nerve Injury ◽  
Axon Regeneration ◽  
Free Medium ◽  
Fast Axonal Transport ◽  
Sensory Axons

A previous study by McLean and co-workers reported that regenerating axons of the rabbit vagus nerve were unable to sustain axonal transport in vitro for several months after nerve injury. In contrast, we found that sensory axons of the rat sciatic nerve were able to transport 3H-labeled protein into their regenerating portions distal to the site of injury within a week after injury when placed in vitro. Transport in vitro was not significantly less than transport in axons maintained in vivo for the same period. Transport occurred in the medium that was used by the McLean group, but was significantly reduced in calcium-free medium. When axon regeneration was delared, only small amounts of activity were present in the nerve distal to the site of injury, showing that labeled protein normally present in that part of the nerve was associated with axons and was not a result of local precursor uptake by nonneural elements in the sciatic nerve. We were not able to explain the failure of McLean and co-workers to demonstrate transport in vitro in regenerating vagus nerve, but we conclude that there is no general peculiarity of growing axons that makes them unable to sustain transport in vitro.

scholarly journals The dynamic changes of main cell types in the microenvironment of sciatic nerves following sciatic nerve injury and the influence of let-7 on their distribution

RSC Advances ◽  
2018 ◽  
Vol 8 (72) ◽  
pp. 41181-41191 ◽  
Author(s):  
Tianmei Qian ◽  
Pan Wang ◽  
Qianqian Chen ◽  
Sheng Yi ◽  
Qianyan Liu ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Cell Types ◽  
Sciatic Nerve Injury ◽  
Dynamic Changes ◽  
Main Cell ◽  
Sciatic Nerves

Schwann cells (SCs), fibroblasts and macrophages are the main cells in the peripheral nerve stumps.

scholarly journals Preparation of Encapsulated Resveratrol Liposome Thermosensitive Gel and Evaluation of Its Capability to Repair Sciatic Nerve Injury in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Hui Yao ◽  
Hao Lu ◽  
Rong Zou ◽  
Xiwen Chen ◽  
Hanlin Xu
Keyword(s):  
Sciatic Nerve ◽  
Nerve Injury ◽  
Drug Loading ◽  
Particle Diameter ◽  
Sciatic Nerve Injury ◽  
Release Time ◽  
Temperature Sensitive ◽  
Polymer Gel ◽  
Injury Model

The purpose of this study was to prepare a liposomal temperature-sensitive gel able to slowly release resveratrol after local intramuscular injection. The best formulation of resveratrol liposomes was based on the highest encapsulation efficiency and drug loading designed by Box-Behnken. The prepared liposomes were approximately circular, with a mean particle diameter of 161.5±0.12 nm and zeta potential of -6.9 mV. The optimized liposomes were dispersed in a polymer gel (PLGA-PEG-PLGA) for preparation of an in situ-formed gel at 35±2°C. In vitro release of the prepared liposome temperature-sensitive gel was studied and compared with ordinary drug-releasing gels, revealing a significantly longer drug release time. Finally, a rat sciatic nerve injury model was used to evaluate the pharmacological activity of the liposome temperature-sensitive gels for the repair of damaged nerves. The results indicate that the gel was able to promote recovery of damaged nerves.

Detergent‐based decellularized peripheral nerve allografts: An in vivo preclinical study in the rat sciatic nerve injury model

2020 ◽  
Vol 14 (6) ◽  
pp. 789-806 ◽  
Author(s):  
Jesús Chato‐Astrain ◽  
Charlot Philips ◽  
Fernando Campos ◽  
Daniel Durand‐Herrera ◽  
Oscar D. García‐García ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Preclinical Study ◽  
Sciatic Nerve Injury ◽  
Rat Sciatic Nerve ◽  
Injury Model

scholarly journals In-vivo analysis of nerve regeneration after sciatic nerve injury in a rat model

2016 ◽  
Vol 3 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Clint Hansen ◽  
Tony M. Dinis ◽  
Guillaume Vidal ◽  
Khalil Ben-Mansour ◽  
Damien Bresson ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Rat Model ◽  
Sciatic Nerve Injury ◽  
In Vivo Analysis

scholarly journals Quantitative Proteomic Analysis of Mouse Sciatic Nerve Reveals Post-injury Upregulation of ADP-Dependent Glucokinase Promoting Macrophage Phagocytosis

2021 ◽  
Vol 14 ◽  
Author(s):  
Kai Zhang ◽  
Qingyao Wang ◽  
Yiyao Liang ◽  
Yu Yan ◽  
Haiqiong Wang ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Injury ◽  
Proteomic Analysis ◽  
Inflammatory Responses ◽  
Post Injury ◽  
Injured Nerve ◽  
Protein Levels ◽  
Macrophage Phagocytosis

Nerve injury induces profound and complex changes at molecular and cellular levels, leading to axonal self-destruction as well as immune and inflammatory responses that may further promote neurodegeneration. To better understand how neural injury changes the proteome within the injured nerve, we set up a mouse model of sciatic nerve injury (SNI) and conducted an unbiased, quantitative proteomic study followed by biochemical assays to confirm some of the changed proteins. Among them, the protein levels of ADP-dependent glucokinase (ADPGK) were significantly increased in the injured sciatic nerve. Further examination indicated that ADPGK was specifically expressed and upregulated in macrophages but not neurons or Schwann cells upon injury. Furthermore, culturing immortalized bone marrow-derived macrophages (iBMDMs) in vitro with the conditioned media from transected axons of mouse dorsal root ganglion (DRG) neurons induced ADPGK upregulation in iBMDMs, suggesting that injured axons could promote ADPGK expression in macrophages non-cell autonomously. Finally, we showed that overexpression of ADPGK per se did not activate macrophages but promoted the phagocytotic activity of lipopolysaccharides (LPS)-treated macrophages. Together, this proteomic analysis reveals interesting changes of many proteins within the injured nerve and our data identify ADPGK as an important in vivo booster of injury-induced macrophage phagocytosis.

scholarly journals In Vitro and In Vivo Effects of Nobiletin on DRG Neurite Elongation and Axon Growth after Sciatic Nerve Injury

2021 ◽  
Vol 18 (17) ◽  
pp. 8988
Author(s):  
Tae-Beom Seo ◽  
Yoon-A Jeon ◽  
Sang Suk Kim ◽  
Young Jae Lee
Keyword(s):  
Sciatic Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Axon Growth ◽  
Sciatic Nerve Injury ◽  
Dependent Manner ◽  
Neurite Elongation ◽  
Sciatic Nerve Regeneration

Sciatic nerve injury (SNI) leads to sensory and motor dysfunctions. Nobiletin is a major component of polymethoxylated flavonoid extracted from citrus fruits. The role of nobiletin on sciatic nerve regeneration is still unclear. Thus, the purpose of this study was to investigate whether nobiletin increases DRG neurite elongation and regeneration-related protein expression after SNI. Cytotoxicity of nobiletin was measured in a concentration–dependent manner using the MTT assay. For an in vitro primary cell culture, the sciatic nerve on the middle thigh was crushed by holding twice with forceps. Dorsal root ganglion (DRG) and Schwann cells were cultured 3 days after SNI and harvested 36 h later and 3 days later, respectively. In order to evaluate specific regeneration-related markers and axon growth in the injured sciatic nerve, we applied immunofluorescence staining and Western blot techniques. Nobiletin increased cell viability in human neuroblastoma cells and inhibited cytotoxicity induced by exposure to H2O2. Mean neurite length of DRG neurons was significantly increased in the nobiletin group at a dose of 50 and 100 μM compared to those at other concentrations. GAP-43, a specific marker for axonal regeneration, was enhanced in injury preconditioned Schwann cells with nobiletin treatment and nobiletin significantly upregulated it in injured sciatic nerve at only 3 days post crush (dpc). In addition, nobiletin dramatically facilitated axonal regrowth via activation of the BDNF-ERK1/2 and AKT pathways. These results should provide evidence to distinguish more accurately the biochemical mechanisms regarding nobiletin-activated sciatic nerve regeneration.

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