Nerve repair: Experimental and clinical evaluation of neurotrophic factors in peripheral nerve regeneration

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.

Download Full-text

Peripheral Nerve Regeneration and Nerve Repair

10.1007/springerreference_118043 ◽

2012 ◽

Cited By ~ 1

Keyword(s):

Peripheral Nerve ◽

Nerve Regeneration ◽

Nerve Repair ◽

Peripheral Nerve Regeneration

Download Full-text

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

Biomaterials Science ◽

10.1039/c7bm01101f ◽

2018 ◽

Vol 6 (5) ◽

pp. 1059-1075 ◽

Cited By ~ 17

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.

Download Full-text

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

Journal of Neurosurgery ◽

10.3171/jns.2003.98.2.0371 ◽

2003 ◽

Vol 98 (2) ◽

pp. 371-377 ◽

Cited By ~ 41

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.

Download Full-text

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

Reviews in the Neurosciences ◽

10.1515/revneuro-2017-0060 ◽

2018 ◽

Vol 29 (4) ◽

pp. 369-376 ◽

Cited By ~ 11

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.

Download Full-text

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

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/5481228 ◽

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.

Download Full-text

Peripheral Nerve Regeneration and Muscle Reinnervation

International Journal of Molecular Sciences ◽

10.3390/ijms21228652 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8652 ◽

Cited By ~ 1

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.

Download Full-text