scholarly journals IL-17F depletion accelerates chitosan conduit guided peripheral nerve regeneration

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Feixiang Chen ◽  
Weihuang Liu ◽  
Qiang Zhang ◽  
Ping Wu ◽  
Ao Xiao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Knockout Mice ◽  
Inflammatory Markers ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Wild Type ◽  
Anti Inflammatory

AbstractPeripheral nerve injury is a serious health problem and repairing long nerve deficits remains a clinical challenge nowadays. Nerve guidance conduit (NGC) serves as the most promising alternative therapy strategy to autografts but its repairing efficiency needs improvement. In this study, we investigated whether modulating the immune microenvironment by Interleukin-17F (IL-17F) could promote NGC mediated peripheral nerve repair. Chitosan conduits were used to bridge sciatic nerve defect in IL-17F knockout mice and wild-type mice with autografts as controls. Our data revealed that IL-17F knockout mice had improved functional recovery and axonal regeneration of sciatic nerve bridged by chitosan conduits comparing to the wild-type mice. Notably, IL-17F knockout mice had enhanced anti-inflammatory macrophages in the NGC repairing microenvironment. In vitro data revealed that IL-17F knockout peritoneal and bone marrow derived macrophages had increased anti-inflammatory markers after treatment with the extracts from chitosan conduits, while higher pro-inflammatory markers were detected in the Raw264.7 macrophage cell line, wild-type peritoneal and bone marrow derived macrophages after the same treatment. The biased anti-inflammatory phenotype of macrophages by IL-17F knockout probably contributed to the improved chitosan conduit guided sciatic nerve regeneration. Additionally, IL-17F could enhance pro-inflammatory factors production in Raw264.7 cells and wild-type peritoneal macrophages. Altogether, IL-17F may partially mediate chitosan conduit induced pro-inflammatory polarization of macrophages during nerve repair. These results not only revealed a role of IL-17F in macrophage function, but also provided a unique and promising target, IL-17F, to modulate the microenvironment and enhance the peripheral nerve regeneration.

scholarly journals Gellan Gum-based luminal fillers for peripheral nerve regeneration: an in vivo study in the rat sciatic nerve repair model

2018 ◽  
Vol 6 (5) ◽  
pp. 1059-1075 ◽  
Author(s):  
C. R. Carvalho ◽  
S. Wrobel ◽  
C. Meyer ◽  
C. Brandenberger ◽  
I. F. Cengiz ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Experimental Work ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Gellan Gum ◽  
In Vivo Study ◽  
Rat Sciatic Nerve

This experimental work considers the innovative use of the biomaterial Gellan Gum (GG) as a luminal filler for nerve guidance channels.

Effects of human amniotic fluid on peripheral nerve scarring and regeneration in rats

2003 ◽  
Vol 98 (2) ◽  
pp. 371-377 ◽  
Author(s):  
Güzin Yeşim Özgenel ◽  
Gülaydan Filiz
Keyword(s):  
Peripheral Nerve ◽  
Amniotic Fluid ◽  
Nerve Regeneration ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Control Group ◽  
Human Amniotic Fluid ◽  
Content Type ◽  
Repair Site ◽  
Fine Print

Object. Peripheral nerve repair surgery is still replete with challenges. Despite technical improvements in microsurgery, classic methods of nerve repair have failed to provide satisfactory results. The purpose of this study was to investigate the effects of amniotic fluid from humans on peripheral nerve scarring and regeneration in rats. Methods. Forty adult Sprague—Dawley rats were used in this study. After the right sciatic nerve in each rat was transected and repaired using an epineural suture procedure, the nerves were divided into two groups according to the solution applied around the repair site: experimental group, 0.3 ml human amniotic fluid (HAF); and control group, 0.3 ml saline. Macroscopic and histological evaluations of peripheral nerve scarring were performed 4 weeks postsurgery. Nerves treated with HAF demonstrated a significant reduction in the amount of scar tissue surrounding the repair site (p < 0.05). No evidence of a reaction against HAF was noted. Functional nerve regeneration was measured once every 2 weeks by using a sciatic function index until 12 weeks postsurgery. Functional recovery in nerves treated with amniotic fluid occurred significantly faster than that in nerves treated with saline (p < 0.05). Peripheral nerve regeneration was evaluated histomorphologically at 12 weeks postsurgery. Nerves treated with amniotic fluid showed significant improvement with respect to the indices of fiber maturation (p < 0.05). Conclusions. Preliminary data show that HAF enhances peripheral nerve regeneration. The preventive effect of HAF on epineural scarring and the rich content of neurotrophic and neurite-promoting factors possibly contribute to this result.

Calcitonin gene-related peptide (CGRP): role in peripheral nerve regeneration

2018 ◽  
Vol 29 (4) ◽  
pp. 369-376 ◽  
Author(s):  
Albert M. Chung
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Calcitonin Gene Related Peptide ◽  
Demyelinating Diseases ◽  
Mitogen Activated Protein Kinase ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Cord Injury

Abstract Calcitonin gene-related peptide (CGRP) is a neuropeptide that has an important anti-inflammatory role in the immune system. Research has shown that CGRP is an integral part in peripheral nerve regeneration by (1) suppressing tumor necrosis factor-α, (2) forming an initial nerve bridge by increasing fibroblast motility and extracellular matrix synthesis, (3) vascularizing the spinal cord injury site, and (4) inducing Schwann cell (SC) proliferation. In this treatise, the following hypotheses will be explored: (1) CGRP is induced by c-Jun to regulate SC dedifferentiation, (2) CGRP promotes the chemotaxic migration of SCs along the nerve bridge, and (3) CGRP induces myelinophagy by activating various signaling pathways, such as p38 mitogen-activated protein kinase and Raf/extracellular signal-regulated kinase. These processes provide a framework for understanding the role of CGRP in peripheral nerve regeneration, which may be important in developing better strategies for nerve repair and gaining further insight into demyelinating diseases.

scholarly journals Fibroblast Growth Factor 13 Facilitates Peripheral Nerve Regeneration through Maintaining Microtubule Stability

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Rui Li ◽  
Xuetao Tao ◽  
Minghong Huang ◽  
Yan Peng ◽  
Jiahong Liang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Fibroblast Growth Factor ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Fibroblast Growth ◽  
Promising Alternative ◽  
Microtubule Stability

Peripheral nerve injury (PNI), resulting in the impairment of myelin sheaths and axons, seriously affects the transmission of sensory or motor nerves. Growth factors (GFs) provide a biological microenvironment for supporting nerve regrowth and have become a promising alternative for repairing PNI. As one number of intracellular growth factor family, fibroblast growth factor 13 (FGF13) was regard as a microtubule-stabilizing protein for regulating cytoskeletal plasticity and neuronal polarization. However, the therapeutic efficiency and underlying mechanism of FGF13 for treating PNI remained unknown. Here, the application of lentivirus that overexpressed FGF13 was delivered directly to the lesion site of transverse sciatic nerve for promoting peripheral nerve regeneration. Through behavioral analysis and histological and ultrastructure examinations, we found that FGF13 not only facilitated motor and sense functional recovery but also enhanced axon elongation and remyelination. Furthermore, pretreatment with FGF13 also promoted Schwann cell (SC) viability and upregulated the expression cellular microtubule-associated proteins in vitro PNI model. These data indicated FGF13 therapeutic effect was closely related to maintain cellular microtubule stability. Thus, this work provides the evident that FGF13-medicated microtubule stability is necessary for promoting peripheral nerve repair following PNI, highlighting the potential therapeutic value of FGF13 on ameliorating injured nerve recovery.

scholarly journals Peripheral Nerve Regeneration and Muscle Reinnervation

2020 ◽  
Vol 21 (22) ◽  
pp. 8652 ◽  
Author(s):  
Tessa Gordon
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Low Frequency ◽  
Nerve Fibers ◽  
Target Organs ◽  
Neuronal Soma ◽  
Original Target ◽  
Surgical Manipulations

Injured peripheral nerves but not central nerves have the capacity to regenerate and reinnervate their target organs. After the two most severe peripheral nerve injuries of six types, crush and transection injuries, nerve fibers distal to the injury site undergo Wallerian degeneration. The denervated Schwann cells (SCs) proliferate, elongate and line the endoneurial tubes to guide and support regenerating axons. The axons emerge from the stump of the viable nerve attached to the neuronal soma. The SCs downregulate myelin-associated genes and concurrently, upregulate growth-associated genes that include neurotrophic factors as do the injured neurons. However, the gene expression is transient and progressively fails to support axon regeneration within the SC-containing endoneurial tubes. Moreover, despite some preference of regenerating motor and sensory axons to “find” their appropriate pathways, the axons fail to enter their original endoneurial tubes and to reinnervate original target organs, obstacles to functional recovery that confront nerve surgeons. Several surgical manipulations in clinical use, including nerve and tendon transfers, the potential for brief low-frequency electrical stimulation proximal to nerve repair, and local FK506 application to accelerate axon outgrowth, are encouraging as is the continuing research to elucidate the molecular basis of nerve regeneration.

Transplantation of olfactory ensheathing cells enhances peripheral nerve regeneration after microsurgical nerve repair

2009 ◽  
Vol 1254 ◽  
pp. 10-17 ◽  
Author(s):  
Christine Radtke ◽  
Ayal A. Aizer ◽  
Samuel K. Agulian ◽  
Karen L. Lankford ◽  
Peter M. Vogt ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Olfactory Ensheathing Cells ◽  
Ensheathing Cells

GELATIN-TRICALCIUM PHOSPHATE MEMBRANE MODIFIED WITH NGF AND CULTURED SCHWANN CELLS FOR PERIPHERAL NERVE REPAIR: A TISSUE ENGINEERING APPROACH

2006 ◽  
Vol 18 (02) ◽  
pp. 47-54 ◽  
Author(s):  
MING-HONG CHEN ◽  
PEI-RU CHEN ◽  
MEI-HSIU CHEN ◽  
SUNG-TSANG HSIEH ◽  
JING-SHAN HUANG ◽  
...  
Keyword(s):  
Growth Factors ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Tricalcium Phosphate ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Nerve Growth ◽  
Nerve Growth Factors ◽  
Cultured Schwann Cells

This study attempted to enhance the efficacy of peripheral nerve regeneration using our previously developed gelatin-tricalcium phosphate (GTG) conduits by incorporating them with nerve growth factors and cultured Schwann cells. The nerve growth factors were covalently immobilized onto the GTG conduits (GEN) using carbodiimide. Schwann cells were harvested from neonatal Lewis rats, cultured for seven days and injected into the GEN conduits. The experiment was performed in three groups: GTG conduits, GEN conduits and GEN conduits with Schwann cells injected (GEN+Sc). The effects of different conduits (GTG, GEN and GEN with Schwann cells) on the peripheral nerve regeneration were evaluated in rat sciatic nerve repair model. 24 weeks after implantation of conduits, degradation of the conduits in all groups was illustrated by the fragmentation of the conduits. All conduits were well tolerated by the host tissue. Under microscopic evaluations, regenerated nerve tissue with myelinated and unmyelinated axons presented in all groups. Histomorphometrically, the total nerve area of GEN+Sc group was significantly higher than GTG group. Conversely, the autotomy score evaluated 12 weeks after nerve repair showed better results for GTG group. Besides, GEN+Sc group had the highest average recovery index of compound muscle action potential, but the difference among each group did not reach statistical significance. Although the electrophysiological recovery of nerve was not significantly improved with GEN+Sc conduit, nerve repair using tissue engineered conduits still provided better histological results. However, it should be noticed that autotomy may be the price paid for enhanced peripheral nerve.

Platelet-Rich Fibrin Conduits as an Alternative to Nerve Autografts for Peripheral Nerve Repair

2017 ◽  
Vol 33 (08) ◽  
pp. 549-556 ◽  
Author(s):  
Marcela Fernandes ◽  
Sandra Valente ◽  
João Santos ◽  
Rebeca Furukawa ◽  
Carlos Fernandes ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Motor Neurons ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Nerve Fibers ◽  
Nerve Graft ◽  
Platelet Rich Fibrin ◽  
Significant Difference ◽  
Autogenous Vein

Background Peripheral nerves have limited regeneration capacity despite best efforts. Platelet-rich fibrin (PRF) contains growth factors that may stimulate peripheral nerve regeneration. This study verified whether nerve regeneration using autogenous vein conduits filled with PRF is comparable to autologous nerve graft, which is the standard treatment. Methods The sciatic nerve of the right paw of inbred rats was dissected, and a 10-mm segment was removed from rats randomized to receive autologous nerve graft (GRAFT) or vein conduit filled with PRF (PRF). A third group (SHAM) underwent surgery without nerve resection. The sciatic functional index (SFI) was measured 0, 30, 60, and 90 days postsurgery. Morphometry and morphology of the distal nerve injury were examined. Motor neurons in the anterior horn of spinal cord stained with FluoroGold and counted. Results No significant difference in SFI was observed between the GRAFT and PRF groups at any time point (all p > 0.05); however, SFI was lower in both groups compared with SHAM (p < 0.05). Morphometric and morphologic indexes were not significantly different between the GRAFT and PRF groups (p > 0.05); however, nerve fibers, axons, and myelin sheaths were thinner in both groups compared with SHAM (p = 0.0001). Average motor neurons' count was similar between the GRAFT and PRF groups (p = 0.91); the count was lower in both groups compared with SHAM (p = 0.002 and p = 0.001), respectively. Conclusion Autologous nerve GRAFT and PRF-filled autogenous vein conduits were associated with similar outcomes, and worse than those observed in SHAM controls. Vein conduits filled with PRF may be a favorable alternative treatment to nerve grafts.

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