scholarly journals Recent Findings on the Effects of Pharmacological Agents on the Nerve Regeneration after Peripheral Nerve Injury

2020 ◽  
Vol 18 (11) ◽  
pp. 1154-1163
Author(s):  
Samira Bolandghamat ◽  
Morteza Behnam-Rassouli
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Molecular Mechanisms ◽  
Functional Disability ◽  
Nerve Repair ◽  
Invasive Treatment ◽  
Pharmacological Agents ◽  
Non Invasive ◽  
Repair Techniques

: Peripheral nerve injuries (PNIs) are accompanied with neuropathic pain and functional disability. Despite improvements in surgical repair techniques in recent years, the functional recovery is yet unsatisfied. Indeed a successful nerve repair depends not only on the surgical strategy but also on the cellular and molecular mechanisms involved in traumatic nerve injury. In contrast to all strategies suggested for nerve repair, pharmacotherapy is a cheap, accessible and non-invasive treatment that can be used immediately after nerve injury. This study aimed to review the effects of some pharmacological agents on the nerve regeneration after traumatic PNI evaluated by functional, histological and electrophysiological assessments. In addition, some cellular and molecular mechanisms responsible for their therapeutic actions, restricted to neural tissue, are suggested. These findings can not only help to find better strategies for peripheral nerve repair, but also to identify the neuropathic effects of various medications and their mechanisms of action.

scholarly journals Mesenchymal Stem Cell Treatment Perspectives in Peripheral Nerve Regeneration: Systematic Review

2021 ◽  
Vol 22 (2) ◽  
pp. 572
Author(s):  
Andrea Lavorato ◽  
Stefania Raimondo ◽  
Marina Boido ◽  
Luisa Muratori ◽  
Giorgia Durante ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
High Survival ◽  
Nerve Lesion ◽  
Differentiation Potential

Traumatic peripheral nerve lesions affect hundreds of thousands of patients every year; their consequences are life-altering and often devastating and cause alterations in movement and sensitivity. Spontaneous peripheral nerve recovery is often inadequate. In this context, nowadays, cell therapy represents one of the most innovative approaches in the field of nerve repair therapies. The purpose of this systematic review is to discuss the features of different types of mesenchymal stem cells (MSCs) relevant for peripheral nerve regeneration after nerve injury. The published literature was reviewed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A combination of the keywords “nerve regeneration”, “stem cells”, “peripheral nerve injury”, “rat”, and “human” were used. Additionally, a “MeSH” research was performed in PubMed using the terms “stem cells” and “nerve regeneration”. The characteristics of the most widely used MSCs, their paracrine potential, targeted stimulation, and differentiation potentials into Schwann-like and neuronal-like cells are described in this paper. Considering their ability to support and stimulate axonal growth, their remarkable paracrine activity, their presumed differentiation potential, their extremely low immunogenicity, and their high survival rate after transplantation, ADSCs appear to be the most suitable and promising MSCs for the recovery of peripheral nerve lesion. Clinical considerations are finally reported.

Role of Central Plasticity in the Outcome of Peripheral Nerve Regeneration

Neurosurgery ◽  
2015 ◽  
Vol 77 (3) ◽  
pp. 418-423 ◽  
Author(s):  
Chandan B. Mohanty ◽  
Dhananjaya Bhat ◽  
Bhagavatula Indira Devi
Keyword(s):  
Clinical Outcome ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Brain Plasticity ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Short Review ◽  
Repair Techniques

Abstract The optimal refinement in nerve repair techniques has reached a plateau, making it imperative to continually explore newer avenues for improving the clinical outcome of peripheral nerve regeneration. The aim of this short review is to discuss the role and mechanism of brain plasticity in nerve regeneration, as well as to explore the possible application of this knowledge for improving the clinical outcome following nerve repair.

scholarly journals Insights Into the Role and Potential of Schwann Cells for Peripheral Nerve Repair From Studies of Development and Injury

2021 ◽  
Vol 13 ◽  
Author(s):  
Anjali Balakrishnan ◽  
Lauren Belfiore ◽  
Tak-Ho Chu ◽  
Taylor Fleming ◽  
Rajiv Midha ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Molecular Mechanisms ◽  
Nerve Repair ◽  
Motor Deficits ◽  
Repair Capacity ◽  
Peripheral Nerve Repair ◽  
Cell Replacement

Peripheral nerve injuries arising from trauma or disease can lead to sensory and motor deficits and neuropathic pain. Despite the purported ability of the peripheral nerve to self-repair, lifelong disability is common. New molecular and cellular insights have begun to reveal why the peripheral nerve has limited repair capacity. The peripheral nerve is primarily comprised of axons and Schwann cells, the supporting glial cells that produce myelin to facilitate the rapid conduction of electrical impulses. Schwann cells are required for successful nerve regeneration; they partially “de-differentiate” in response to injury, re-initiating the expression of developmental genes that support nerve repair. However, Schwann cell dysfunction, which occurs in chronic nerve injury, disease, and aging, limits their capacity to support endogenous repair, worsening patient outcomes. Cell replacement-based therapeutic approaches using exogenous Schwann cells could be curative, but not all Schwann cells have a “repair” phenotype, defined as the ability to promote axonal growth, maintain a proliferative phenotype, and remyelinate axons. Two cell replacement strategies are being championed for peripheral nerve repair: prospective isolation of “repair” Schwann cells for autologous cell transplants, which is hampered by supply challenges, and directed differentiation of pluripotent stem cells or lineage conversion of accessible somatic cells to induced Schwann cells, with the potential of “unlimited” supply. All approaches require a solid understanding of the molecular mechanisms guiding Schwann cell development and the repair phenotype, which we review herein. Together these studies provide essential context for current efforts to design glial cell-based therapies for peripheral nerve regeneration.

scholarly journals Therapeutic Low-Intensity Ultrasound for Peripheral Nerve Regeneration – A Schwann Cell Perspective

2022 ◽  
Vol 15 ◽  
Author(s):  
Jenica Acheta ◽  
Shannon B. Z. Stephens ◽  
Sophie Belin ◽  
Yannick Poitelon
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Molecular Mechanisms ◽  
Peripheral Nerve Regeneration ◽  
Small Population ◽  
Low Intensity ◽  
Low Intensity Ultrasound

Peripheral nerve injuries are common conditions that can arise from trauma (e.g., compression, severance) and can lead to neuropathic pain as well as motor and sensory deficits. Although much knowledge exists on the mechanisms of injury and nerve regeneration, treatments that ensure functional recovery following peripheral nerve injury are limited. Schwann cells, the supporting glial cells in peripheral nerves, orchestrate the response to nerve injury, by converting to a “repair” phenotype. However, nerve regeneration is often suboptimal in humans as the repair Schwann cells do not sustain their repair phenotype long enough to support the prolonged regeneration times required for successful nerve regrowth. Thus, numerous strategies are currently focused on promoting and extending the Schwann cells repair phenotype. Low-intensity ultrasound (LIU) is a non-destructive therapeutic approach which has been shown to facilitate peripheral nerve regeneration following nerve injury in rodents. Still, clinical trials in humans are scarce and limited to small population sizes. The benefit of LIU on nerve regeneration could possibly be mediated through the repair Schwann cells. In this review, we discuss the known and possible molecular mechanisms activated in response to LIU in repair Schwann cells to draw support and attention to LIU as a compelling regenerative treatment for peripheral nerve injury.

scholarly journals Mechanisms of Schwann cell plasticity involved in peripheral nerve repair after injury

2020 ◽  
Vol 77 (20) ◽  
pp. 3977-3989 ◽  
Author(s):  
Gianluigi Nocera ◽  
Claire Jacob
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Critical Feature ◽  
Axonal Regrowth ◽  
De Novo Genes ◽  
Dynamic Cell

Abstract The great plasticity of Schwann cells (SCs), the myelinating glia of the peripheral nervous system (PNS), is a critical feature in the context of peripheral nerve regeneration following traumatic injuries and peripheral neuropathies. After a nerve damage, SCs are rapidly activated by injury-induced signals and respond by entering the repair program. During the repair program, SCs undergo dynamic cell reprogramming and morphogenic changes aimed at promoting nerve regeneration and functional recovery. SCs convert into a repair phenotype, activate negative regulators of myelination and demyelinate the damaged nerve. Moreover, they express many genes typical of their immature state as well as numerous de-novo genes. These genes modulate and drive the regeneration process by promoting neuronal survival, damaged axon disintegration, myelin clearance, axonal regrowth and guidance to their former target, and by finally remyelinating the regenerated axon. Many signaling pathways, transcriptional regulators and epigenetic mechanisms regulate these events. In this review, we discuss the main steps of the repair program with a particular focus on the molecular mechanisms that regulate SC plasticity following peripheral nerve injury.

Exosomes as a promising therapeutic strategy for peripheral nerve injury

2021 ◽  
Vol 19 ◽  
Author(s):  
Tianhao Yu ◽  
Yingxi Xu ◽  
Muhammad Arslan Ahmad ◽  
Rabia Javed ◽  
Haruo Hagiwara ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Nerve Repair ◽  
Peripheral Nerve Repair ◽  
Nerve Grafts ◽  
Axonal Regrowth ◽  
Vascular Regeneration

Peripheral nerve injury has a high incidence and often leads to severe losses of sensory and motor functions in the afflicted limb. Autologous nerve grafts are widely accepted as the gold standard for peripheral nerve repair, but the presence of inherent drawbacks dramatically reduces their usability. Numerous tissue engineering nerve grafts are developed as alternatives of autologous nerve grafts, and a variety of cells and neurotrophic factors were introduced into these grafts for improvement. However, they are still difficult to obtain satisfactory clinical results. Peripheral nerve regeneration following injury remains a significant challenge for researchers and clinicians. Exosomes are extracellular membranous nanovesicles that are secreted by most cells. As the key players of intercellular communication, exosomes play a fundamental role in the physiological and pathological processes of the nervous system. Accumulating evidence has suggested that exosomes can exert neurotherapeutic effects via mediating axonal regrowth, Schwann cell activation, vascular regeneration, and inflammatory regulation. Exosomes are emerging as a promising approach for treating peripheral nerve injury. Furthermore, they also provide possibilities for enhancing the repair capacity of various nerve grafts. This review primarily highlights the regenerative effects of exosomes on peripheral nerve injury. The exosomes from distinct sources reported so far in literature are summarized to understand their roles in the process of nerve repair. Moreover, the challenges that must be addressed in their clinical transformation are outlined as well. This review also provides further insight into the potential application of exosomes for peripheral nerve repair. Keywords: Exosome, nerve regeneration, peripheral nerve injury, Schwann cell, axonal regrowth, inflammation, vascular regeneration.

scholarly journals Coordinated changes in the expression of Wnt pathway genes following human and rat peripheral nerve injury

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249748
Author(s):  
Arie C. van Vliet ◽  
Jinhui Lee ◽  
Marlijn van der Poel ◽  
Matthew R. J. Mason ◽  
Jasprina N. Noordermeer ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Peripheral Nerve Regeneration ◽  
Gene Clusters ◽  
Nerve Lesion ◽  
Injured Nerve ◽  
Wnt Ligands

A human neuroma-in continuity (NIC), formed following a peripheral nerve lesion, impedes functional recovery. The molecular mechanisms that underlie the formation of a NIC are poorly understood. Here we show that the expression of multiple genes of the Wnt family, including Wnt5a, is changed in NIC tissue from patients that underwent reconstructive surgery. The role of Wnt ligands in NIC pathology and nerve regeneration is of interest because Wnt ligands are implicated in tissue regeneration, fibrosis, axon repulsion and guidance. The observations in NIC prompted us to investigate the expression of Wnt ligands in the injured rat sciatic nerve and in the dorsal root ganglia (DRG). In the injured nerve, four gene clusters were identified with temporal expression profiles corresponding to particular phases of the regeneration process. In the DRG up- and down regulation of certain Wnt receptors suggests that nerve injury has an impact on the responsiveness of injured sensory neurons to Wnt ligands in the nerve. Immunohistochemistry showed that Schwann cells in the NIC and in the injured nerve are the source of Wnt5a, whereas the Wnt5a receptor Ryk is expressed by axons traversing the NIC. Taken together, these observations suggest a central role for Wnt signalling in peripheral nerve regeneration.

scholarly journals A case of nerve repair using a conduit for peripheral nerve regeneration (Nerbridge®) with lingual nerve injury

2020 ◽  
Vol 66 (4) ◽  
pp. 188-193
Author(s):  
Akihiro NISHIYAMA ◽  
Takahiko SHIBAHARA ◽  
Kenichi SASAKI ◽  
Masayuki TAKANO ◽  
Kenichi MASTUZAKA ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Lingual Nerve

scholarly journals Imaging in the repair of peripheral nerve injury

Nanomedicine ◽  
2019 ◽  
Vol 14 (20) ◽  
pp. 2659-2677 ◽  
Author(s):  
Igor D Luzhansky ◽  
Leland C Sudlow ◽  
David M Brogan ◽  
Matthew D Wood ◽  
Mikhail Y Berezin
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Surgical Guidance ◽  
Injury Treatment ◽  
Low Toxicity ◽  
Recovery Monitoring

Surgical intervention followed by physical therapy remains the major way to repair damaged nerves and restore function. Imaging constitutes promising, yet underutilized, approaches to improve surgical and postoperative techniques. Dedicated methods for imaging nerve regeneration will potentially provide surgical guidance, enable recovery monitoring and postrepair intervention, elucidate failure mechanisms and optimize preclinical procedures. Herein, we present an outline of promising innovations in imaging-based tracking of in vivo peripheral nerve regeneration. We emphasize optical imaging because of its cost, versatility, relatively low toxicity and sensitivity. We discuss the use of targeted probes and contrast agents (small molecules and nanoparticles) to facilitate nerve regeneration imaging and the engineering of grafts that could be used to track nerve repair. We also discuss how new imaging methods might overcome the most significant challenges in nerve injury treatment.

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