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Neurosurgical Focus Feb 2009Nerve tubes, guides, or conduits are a promising alternative for autologous nerve graft repair. The first biodegradable empty single lumen or hollow nerve tubes are... (Review)
Review
Nerve tubes, guides, or conduits are a promising alternative for autologous nerve graft repair. The first biodegradable empty single lumen or hollow nerve tubes are currently available for clinical use and are being used mostly in the repair of small-diameter nerves with nerve defects of < 3 cm. These nerve tubes are made of different biomaterials using various fabrication techniques. As a result these tubes also differ in physical properties. In addition, several modifications to the common hollow nerve tube (for example, the addition of Schwann cells, growth factors, and internal frameworks) are being investigated that may increase the gap that can be bridged. This combination of chemical, physical, and biological factors has made the design of a nerve conduit into a complex process that demands close collaboration of bioengineers, neuroscientists, and peripheral nerve surgeons. In this article the authors discuss the different steps that are involved in the process of the design of an ideal nerve conduit for peripheral nerve repair.
Topics: Absorbable Implants; Guided Tissue Regeneration; Humans; Interdisciplinary Communication; Materials Testing; Nerve Growth Factors; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Peripheral Nervous System Diseases; Polymers; Schwann Cells
PubMed: 19435445
DOI: 10.3171/FOC.2009.26.2.E5 -
Anatomical Record (Hoboken, N.J. : 2007) Aug 2019Peripherally projecting neurons undergo significant morphological changes during development and regeneration. This neuroplasticity is controlled by growth factors,... (Review)
Review
Peripherally projecting neurons undergo significant morphological changes during development and regeneration. This neuroplasticity is controlled by growth factors, which bind specific membrane bound kinase receptors that in turn activate two major intracellular signal transduction cascades. Besides the PI3 kinase/AKT pathway, activated extracellular signal-regulated kinase (ERK) plays a key role in regulating the mode and speed of peripheral axon outgrowth in the adult stage. Cell culture studies and animal models revealed that ERK signaling is mainly involved in elongative axon growth in vitro and long-distance nerve regeneration in vivo. Here, we review ERK dependent morphological plasticity in adult peripheral neurons and evaluate the therapeutic potential of interfering with regulators of ERK signaling to promote nerve regeneration. Anat Rec, 302:1261-1267, 2019. © 2019 Wiley Periodicals, Inc.
Topics: Animals; Extracellular Signal-Regulated MAP Kinases; Humans; MAP Kinase Signaling System; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves
PubMed: 30951263
DOI: 10.1002/ar.24126 -
Cellular Physiology and Biochemistry :... 2018Myelination, degeneration and regeneration are implicated in crucial responses to injury in the peripheral nervous system. Considering the progression of amyotrophic...
BACKGROUND
Myelination, degeneration and regeneration are implicated in crucial responses to injury in the peripheral nervous system. Considering the progression of amyotrophic lateral sclerosis (ALS), we used the superoxide dismutase 1 (SOD1)-G93A transgenic mouse model of ALS to investigate the effects of mutant SOD1 on the peripheral nerves.
METHODS
Changes in peripheral nerve morphology were analyzed in SOD1 mutant mice at various stages of the disease by toluidine blue staining and electron microscopy (EM). Schwann cell proliferation and recruitment of inflammatory factors were detected by immunofluorescence staining and quantitative reverse transcription PCR and were compared between SOD1 mutant mice and control mice. Furthermore, western blotting (WB) and TUNEL staining were used to investigate axonal damage and Schwann cell survival in the sciatic nerves of mice in both groups.
RESULTS
An analysis of the peripheral nervous system in SOD1-G93A mice revealed the following novel features: (i) Schwann cells and axons in mutant mice underwent changes that were similar to those seen in the control mice during the early development of peripheral nerves. (ii) The peripheral nerves of SOD1-G93A mice developed progressive neuropathy, which presented as defects in axons and myelin, leading to difficulty in walking and reduced locomotor capacity at a late stage of the disease. (iii) Macrophages were recruited and accumulated, and nerve injury and a deficit in the blood-nerve barrier were observed. (iv) Proliferation and the inflammatory micro-environment were inhibited, which impaired the regeneration and remyelination of axons after crush injury in the SOD1-G93A mice.
CONCLUSIONS
The mutant human SOD1 protein induced axonal and myelin degeneration during the progression of ALS and participated in axon remyelination and regeneration in response to injury.
Topics: Amyotrophic Lateral Sclerosis; Animals; Axons; Disease Models, Animal; Disease Progression; Humans; Mice; Mice, Transgenic; Nerve Regeneration; Peripheral Nerves; Point Mutation; Schwann Cells; Superoxide Dismutase; Superoxide Dismutase-1
PubMed: 29742495
DOI: 10.1159/000489627 -
Hand (New York, N.Y.) Mar 2023Acellular nerve allografts have been used successfully and with increasing frequency to reconstruct nerve injuries. As their use has been expanded to treat longer gap,...
BACKGROUND
Acellular nerve allografts have been used successfully and with increasing frequency to reconstruct nerve injuries. As their use has been expanded to treat longer gap, larger diameter nerve injuries, some failed cases have been reported. We present the histomorphometry of 5 such cases illustrating these limitations and review the current literature of acellular nerve allografts.
METHODS
Between 2014 and 2019, 5 patients with iatrogenic nerve injuries to the median or ulnar nerve reconstructed with an AxoGen AVANCE nerve allograft at an outside hospital were treated in our center with allograft excision and alternative reconstruction. These patients had no clinical or electrophysiological evidence of recovery, and allograft specimens at the time of surgery were sent for histomorphological examination.
RESULTS
Three patients with a median and 2 with ulnar nerve injury were included. Histology demonstrated myelinated axons present in all proximal native nerve specimens. In 2 cases, axons failed to regenerate into the allograft and in 3 cases, axonal regeneration diminished or terminated within the allograft.
CONCLUSIONS
The reported cases demonstrate the importance of evaluating the length and the function of nerves undergoing acellular nerve allograft repair. In long length, large-diameter nerves, the use of acellular nerve allografts should be carefully considered.
Topics: Humans; Peripheral Nerve Injuries; Allografts; Nerve Regeneration; Transplantation, Homologous; Peripheral Nerves
PubMed: 33880944
DOI: 10.1177/15589447211003175 -
Journal of Cellular and Molecular... Jan 2019Seeking for effective drugs which are beneficial to facilitating axonal regrowth and elongation after peripheral nerve injury (PNI) has gained extensive attention....
Seeking for effective drugs which are beneficial to facilitating axonal regrowth and elongation after peripheral nerve injury (PNI) has gained extensive attention. Fibroblast growth factor 21 (FGF21) is a metabolic factor that regulates blood glucose and lipid homeostasis. However, there is little concern for the potential protective effect of FGF21 on nerve regeneration after PNI and revealing related molecular mechanisms. Here, we firstly found that exogenous FGF21 administration remarkably promoted functional and morphologic recovery in a rat model of sciatic crush injury, manifesting as persistently improved motor and sensory function, enhanced axonal remyelination and regrowth and accelerated Schwann cells (SCs) proliferation. Furthermore, local FGF21 application attenuated the excessive activation of oxidative stress, which was accompanied with the activation of nuclear factor erythroid-2-related factor 2 (Nrf-2) transcription and extracellular regulated protein kinases (ERK) phosphorylation. We detected FGF21 also suppressed autophagic cell death in SCs. Additionally, treatment with the ERK inhibitor U0126 or autophagy inhibitor 3-MA partially abolishes anti-oxidant effect and reduces SCs death. Taken together, these results indicated that the role of FGF21 in remyelination and nerve regeneration after PNI was probably related to inhibit the excessive activation of ERK/Nrf-2 signalling-regulated oxidative stress and autophagy-induced cell death. Overall, our work suggests that FGF21 administration may provide a new therapy for PNI.
Topics: Animals; Antioxidants; Autophagic Cell Death; Axons; Cell Proliferation; Cells, Cultured; Fibroblast Growth Factors; Male; NF-E2-Related Factor 2; Nerve Regeneration; Oxidative Stress; Peripheral Nerve Injuries; Peripheral Nerves; Rats; Rats, Sprague-Dawley; Remyelination; Schwann Cells; Sciatic Nerve; Signal Transduction
PubMed: 30450828
DOI: 10.1111/jcmm.13952 -
International Journal of Molecular... Jan 2023Despite advances in microsurgery, full functional recovery of severe peripheral nerve injuries is not commonly attained. The sheep appears as a good preclinical model...
Despite advances in microsurgery, full functional recovery of severe peripheral nerve injuries is not commonly attained. The sheep appears as a good preclinical model since it presents nerves with similar characteristics to humans. In this study, we induced 5 or 7 cm resection in the peroneal nerve and repaired with an autograft. Functional evaluation was performed monthly. Electromyographic and ultrasound tests were performed at 6.5 and 9 months postoperation (mpo). No significant differences were found between groups with respect to functional tests, although slow improvements were seen from 5 mpo. Electrophysiological tests showed compound muscle action potentials (CMAP) of small amplitude at 6.5 mpo that increased at 9 mpo, although they were significantly lower than the contralateral side. Ultrasound tests showed significantly reduced size of tibialis anterior (TA) muscle at 6.5 mpo and partially recovered size at 9 mpo. Histological evaluation of the grafts showed good axonal regeneration in all except one sheep from autograft 7 cm (AG7) group, while distal to the graft there was a higher number of axons than in control nerves. The results indicate that sheep nerve repair is a useful model for investigating long-gap peripheral nerve injuries.
Topics: Humans; Sheep; Animals; Peripheral Nerve Injuries; Peripheral Nerves; Peroneal Nerve; Axons; Nerve Regeneration; Sciatic Nerve
PubMed: 36674848
DOI: 10.3390/ijms24021333 -
Neurologia Medico-chirurgica Apr 2000In this review, various conventional nerve repair techniques including direct epineurial repair, grouped fascicular repair, fascicular repair, and nerve grafting are... (Review)
Review
In this review, various conventional nerve repair techniques including direct epineurial repair, grouped fascicular repair, fascicular repair, and nerve grafting are described. The indications for use, as well as the relative advantage and disadvantage, of each technique are discussed. The experimental and clinical evidence from a review of the pertinent literature does not demonstrate a significant difference in outcome of one method over the others. Surgical decisions should be made by a thorough evaluation of all aspects of the nerve injury and surgical methods. All nerve injuries cannot be repaired using only one type of nerve repair method. The surgeon should be familiar with all the techniques described and be prepared to use them under appropriate circumstances.
Topics: Humans; Nerve Regeneration; Nerve Transfer; Peripheral Nerve Injuries; Peripheral Nerves; Tissue Transplantation; Transplantation, Autologous
PubMed: 10853317
DOI: 10.2176/nmc.40.187 -
International Journal of Molecular... Mar 2022A growing body of studies indicate that small noncoding RNAs, especially microRNAs (miRNA), play a crucial role in response to peripheral nerve injuries. During...
A growing body of studies indicate that small noncoding RNAs, especially microRNAs (miRNA), play a crucial role in response to peripheral nerve injuries. During Wallerian degeneration and regeneration processes, they orchestrate several pathways, in particular the MAPK, AKT, and EGR2 (KROX20) pathways. Certain miRNAs show specific expression profiles upon a nerve lesion correlating with the subsequent nerve regeneration stages such as dedifferentiation and with migration of Schwann cells, uptake of debris, neurite outgrowth and finally remyelination of regenerated axons. This review highlights (a) the specific expression profiles of miRNAs upon a nerve lesion and (b) how miRNAs regulate nerve regeneration by acting on distinct pathways and linked proteins. Shedding light on the role of miRNAs associated with peripheral nerve regeneration will help researchers to better understand the molecular mechanisms and deliver targets for precision medicine.
Topics: Humans; MicroRNAs; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Schwann Cells; Sciatic Nerve
PubMed: 35408800
DOI: 10.3390/ijms23073440 -
Development (Cambridge, England) Jul 2011In peripheral nerves, Schwann cells form the myelin sheath that insulates axons and allows rapid propagation of action potentials. Although a number of regulators of...
In peripheral nerves, Schwann cells form the myelin sheath that insulates axons and allows rapid propagation of action potentials. Although a number of regulators of Schwann cell development are known, the signaling pathways that control myelination are incompletely understood. In this study, we show that Gpr126 is essential for myelination and other aspects of peripheral nerve development in mammals. A mutation in Gpr126 causes a severe congenital hypomyelinating peripheral neuropathy in mice, and expression of differentiated Schwann cell markers, including Pou3f1, Egr2, myelin protein zero and myelin basic protein, is reduced. Ultrastructural studies of Gpr126-/- mice showed that axonal sorting by Schwann cells is delayed, Remak bundles (non-myelinating Schwann cells associated with small caliber axons) are not observed, and Schwann cells are ultimately arrested at the promyelinating stage. Additionally, ectopic perineurial fibroblasts form aberrant fascicles throughout the endoneurium of the mutant sciatic nerve. This analysis shows that Gpr126 is required for Schwann cell myelination in mammals, and defines new roles for Gpr126 in axonal sorting, formation of mature non-myelinating Schwann cells and organization of the perineurium.
Topics: Animals; Cochlear Nerve; Early Growth Response Protein 2; Immunohistochemistry; Mice; Mice, Knockout; Microscopy, Electron, Transmission; Myelin Basic Protein; Myelin P0 Protein; Octamer Transcription Factor-6; Peripheral Nerves; Peripheral Nervous System Diseases; Receptors, G-Protein-Coupled; Reverse Transcriptase Polymerase Chain Reaction; Schwann Cells
PubMed: 21613327
DOI: 10.1242/dev.062224 -
International Journal of Molecular... Nov 2020Schwann cells, the most abundant glial cells of the peripheral nervous system, represent the key players able to supply extracellular microenvironment for axonal... (Review)
Review
Schwann cells, the most abundant glial cells of the peripheral nervous system, represent the key players able to supply extracellular microenvironment for axonal regrowth and restoration of myelin sheaths on regenerating axons. Following nerve injury, Schwann cells respond adaptively to damage by acquiring a new phenotype. In particular, some of them localize in the distal stump to form the Bungner band, a regeneration track in the distal site of the injured nerve, whereas others produce cytokines involved in recruitment of macrophages infiltrating into the nerve damaged area for axonal and myelin debris clearance. Several neurotrophic factors, including pituitary adenylyl cyclase-activating peptide (PACAP), promote survival and axonal elongation of injured neurons. The present review summarizes the evidence existing in the literature demonstrating the autocrine and/or paracrine action exerted by PACAP to promote remyelination and ameliorate the peripheral nerve inflammatory response following nerve injury.
Topics: Animals; Axons; Cell Survival; Humans; Myelin Sheath; Nerve Fibers; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Pituitary Adenylate Cyclase-Activating Polypeptide; Schwann Cells; Trauma, Nervous System
PubMed: 33153152
DOI: 10.3390/ijms21218233