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.

scholarly journals Salidroside promotes sciatic nerve regeneration following combined application epimysium conduit and Schwann cells in rats

2020 ◽  
Vol 245 (6) ◽  
pp. 522-531
Author(s):  
Jiaqi Li ◽  
Yongguang Zhang ◽  
Zhimin Yang ◽  
Jingxian Zhang ◽  
Ren Lin ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Western Blot ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Motor Function ◽  
Nerve Conduit ◽  
Combined Application ◽  
Post Operation ◽  
Sciatic Nerve Regeneration

Schwann cell and nerve conduit are crucial for nerve regeneration and re-myelination after peripheral nerves injury. To investigate the effects of Salidroside on autogenous epimysium conduit mixed with BD matrigel and RSC96 Schwann cells on an animal model with 5 mm sciatic nerve defect injury in rat, motor function, muscle reinnervation, immunohistochemical staining, retrograded tracing and Western blot were used in this study. The results showed that Salidroside enhanced the compound effects of epimysium conduit mixed with BD matrigel and RSC96 Schwann cells to improve the sciatic functional index and the gastrocnemius muscle weight ratio, which were better than EPM group at 8 weeks and 12 weeks post operation. Immunofluorescence and Western blot results of P75NTR showed that Salidroside improved the sciatic nerve regeneration, and retrograded tracing of CTB-Alexa 488 also supported that Salidroside was better to promote CTB tracer transporting from the distal nerve defect to the ipsilateral dorsal root ganglion and ventral horn of L3-L5 spinal cord on post-operation 8 weeks and 12 weeks. Our results demonstrated that Salidroside improved the effect of autogenous epimysium conduit mixed with BD matrigel and RSC96 Schwann cells on sciatic nerve regeneration in our study. Impact statement Peripheral nerve injury and regeneration remain a major challenge. Although nerve conduit and Schwann cells have been used to study the nerve regeneration, our results demonstrated that Salidroside improved the regenerative effect in a rat model with sciatic nerve injury model, following a combined application of autogenous epimysium conduit mixed with Schwann cells. Different concentrations of Salidroside combining autogenous epimysium conduit and Schwann cells were applied to compare the epimysium conduit group and the epimysium conduit combining Schwann cells group. Based on the results of motor function and muscle reinnervation evaluation, as well as neuronal tracing and expression of P75NTR, our study for the first time suggests that Salidroside may improve the regeneration effect on the sciatic nerve following a combined application of epimysium conduit and RSC96 Schwann cells in rats.

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.

Sciatic Nerve Regeneration in Mice Induced by Transplantation of in Vitro Differentiated Nucleus Pulposus Progenitor Cells

2014 ◽  
Vol 4 (1_suppl) ◽  
pp. s-0034-1376535-s-0034-1376535
Author(s):  
T. Ishii ◽  
D. Sakai ◽  
T. Nukaga ◽  
J. Mochida
Keyword(s):  
Sciatic Nerve ◽  
Nerve Regeneration ◽  
Progenitor Cells ◽  
Nucleus Pulposus ◽  
Sciatic Nerve Regeneration

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 Dexmedetomidine to Help Nerve Regeneration in a Rat Sciatic Nerve Injury Model

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Wook Jeong ◽  
Hsichiang Kung ◽  
Chia Chi Cheng ◽  
Changwoo Lim ◽  
Min Jung Jung ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Peripheral Nerve Regeneration ◽  
Sciatic Nerve Injury ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Adrenoceptor Agonist ◽  
Group 3 ◽  
Group 2

Background. Several studies have shown that dexmedetomidine (DXM), a selective α2-adrenoceptor agonist, also has neuroprotective effects. However, its effect on impaired peripheral nerve regeneration has not been studied. Materials and Methods. Forty-five Sprague-Dawley rats were randomly assigned to three groups: group 1 (control SHAM), group 2 (sciatic nerve injury + normal saline), and group 3 (sciatic nerve injury + DXM). The rats of group 3 were subdivided into the following three groups: DXM 0.5, 6, and 20 μg·kg−1 (groups 3A, 3B, and 3C, resp.). The sciatic nerve injury was assessed for nerve regeneration at 2 and 6 weeks. Results. There were no differences between groups 2 and 3 in their sciatic functional index (SFI) values or histological findings at 2 weeks postinjury. However, SFI differences were statistically significant at 6 weeks postinjury in group 3. The gross findings with H&E staining showed that the number of axons was higher in group 3 than in group 2. There was no histological difference according to the DXM concentration. Conclusion. The coincidental functional and histological assessment results of this study suggest that DXM for 6 weeks positively affects damaged peripheral nerves.

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.

MIF/CD74 axis participates in inflammatory activation of Schwann cells following sciatic nerve injury

2019 ◽  
Vol 50 (4) ◽  
pp. 355-367 ◽  
Author(s):  
Honghua Song ◽  
Ziwen Zhu ◽  
Yue Zhou ◽  
Nan Du ◽  
Tiancheng Song ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Sciatic Nerve Injury ◽  
Inflammatory Activation

IL-6/STAT3 growth signalling induced by exercise conditioning promotes regeneration of injured rat sciatic nerve: return to an old cytokine

2017 ◽  
Vol 13 (1) ◽  
pp. 45-52
Author(s):  
H. Ashour ◽  
L.A. Rashed ◽  
M.M. Sabry
Keyword(s):  
Sciatic Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Compound Muscle Action Potential ◽  
Tissue Expression ◽  
Sciatic Nerve Injury ◽  
Nerve Tissue ◽  
Injury Group ◽  
Growth Promoting ◽  
Nerve Muscle

The effects of interleukin-6 (IL-6), a growth promoting myokine through signal transduction, and activator of transcription 3 (STAT3), as a growth promoting signal, in peripheral nerve injury (PNI) are still unclear, including whether exercise pre- and/or post-conditioning are useful in nerve regeneration. Four groups were included in the study: sham for sciatic nerve injury (control), sciatic nerve injury group (SNI), exercise post-conditioning (SNI+Ex) and exercise pre- and post-conditioning (Ex+SNI+Ex). IL-6 levels were measured in serum, muscle, nerve and its surrounding fascia. Elevated levels of IL-6 in serum, nerve, muscle and fascia revealed that IL-6 induced in nerve by exercise were: (1) local nerve tissue expression; (2) serum diffused as a myokine from contracting muscle; and (3) diffused for surrounding peri-tendinous region. Evaluation of nerve functions shows that, exercise post-conditioning significantly improved (P<0.05) nerve functions in the form of nerve conduction velocity (NCV) (19.21±4.30 vs 10.96±3.08 m/s), compound muscle action potential amplitude (CMAP) (0.26±0.06 vs 0.18±0.06 mv), histologic improvement in myelination% (35.63±3.92 vs 21.13±4.26) and number of nerve fibres (181.75±9.6 vs 145.75±9.67). However, combined pre- and post-conditioning improved NCV (26.95±2.41 vs 19.21±4.30 m/s) and % myelination (43.50±3.16 vs 35.63±3.92) (P<0.05) when compared with the exercise post-conditioning group. In conclusion, IL-6 induced by exercise is valuable in nerve regeneration. The IL-6/STAT3 growth pathway could be a treatment target in clinical trials in PNI conditions.

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