Peripheral nerve reconstruction after injury: a review of clinical and experimental therapies.
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ABSTRACT:
SUBMITTER: Grinsell D
PROVIDER: S-EPMC4167952 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Peripheral nerve injury can lead to great morbidity in those afflicted, ranging from sensory loss, motor loss, chronic pain, or a combination of deficits. Over time, research has investigated neuronal molecular mechanisms implicated in nerve damage, classified nerve injury, and developed surgical techniques for treatment. Despite these advancements, full functional recovery remains less than ideal. In this review, we discuss historical aspects of peripheral nerve injury and introduce nerve transfer as a therapeutic option, as well as an adjunct therapy to transplantation of Schwann cells and their stem cell derivatives for repair of the damaged nerve. This review furthermore, will provide an elaborated discussion on the sources of Schwann cells, including sites to harvest their progenitor and stem cell lines. This reflects the accessibility to an additional, concurrent treatment approach with nerve transfers that, predicated on related research, may increase the efficacy of the current approach. We then discuss the experimental and clinical investigations of both Schwann cells and nerve transfer that are underway. Lastly, we provide the necessary consideration that these two lines of therapeutic approaches should not be exclusive, but conversely, should be pursued as a combined modality given their mutual role in peripheral nerve regeneration.
| S-EPMC5187901 | biostudies-literature
Project description:Neuropathic pain is one of the most severe forms of chronic pain caused by the direct injury of the somatosensory system. The current drugs for treating neuropathies have limited efficacies or show important side effects, and the development of analgesics with novel modes of action is critical. The identification of endogenous anti-nociceptive factors has emerged as an attractive strategy for designing new pharmacological approaches to treat neuropathic pain. Cortistatin is a neuropeptide with potent anti-inflammatory activity, recently identified as a natural analgesic peptide in several models of pain evoked by inflammatory conditions. Here, we investigated the potential analgesic effect of cortistatin in neuropathic pain using a variety of experimental models of peripheral nerve injury caused by chronic constriction or partial transection of the sciatic nerve or by diabetic neuropathy. We found that the peripheral and central injection of cortistatin ameliorated hyperalgesia and allodynia, two of the dominant clinical manifestations of chronic neuropathic pain. Cortistatin-induced analgesia was multitargeted, as it regulated the nerve damage-induced hypersensitization of primary nociceptors, inhibited neuroinflammatory responses, and enhanced the production of neurotrophic factors both at the peripheral and central levels. We also demonstrated the neuroregenerative/protective capacity of cortistatin in a model of severe peripheral nerve transection. Interestingly, the nociceptive system responded to nerve injury by secreting cortistatin, and a deficiency in cortistatin exacerbated the neuropathic pain responses and peripheral nerve dysfunction. Therefore, cortistatin-based therapies emerge as attractive alternatives for treating chronic neuropathic pain of different etiologies.
| S-EPMC8309056 | biostudies-literature
Project description:BackgroundPeripheral nerve injury (PNI) is common, leading to reduced function, pain, and psychological impact. Treatment has not progressed partly due to inability to compare outcomes between centers managing PNI. Numerous outcome measures exist but there is no consensus on which outcome measures to use nor when.ObjectiveTo perform a systematic review in order to describe and classify outcome measures used in PNI.MethodsA search of Ovid Medline, Ovid Embase, Allied and Complementary Medicine Database (AMED), and CENTRAL (Cochrane Clinical Trials) was conducted. Randomized control trials (RCTs), cohort studies, and case-controlled and case series (≥5 participants) published from inception of the database until 2019 investigating adult patients with a traumatic upper limb PNI in which an outcome measurement was utilized were included.ResultsA total of 96 studies were included (15 RCTs, 8 case-control studies, 18 cohort studies, 5 observational studies, and the remainder were case series or retrospective reviews). A total of 56 individual outcome measures were identified, utilized across 28 different countries and 7097 patients. Ten core domains were defined: sensory subjective, sensory objective, motor subjective, motor objective, sensorimotor function, psychology and well-being, disability, quality of life, pain and discomfort, and neurotrophic measures.ConclusionLack of consensus on outcome measure use hinders comparison of outcomes between nerve injury centers and the development of novel treatments. Development of a core outcome set will help standardize outcome reporting, improve translation of novel treatments from lab to clinical practice, and ensure future research in PNI is more amenable to systematic review and meta-analysis.
| S-EPMC8203424 | biostudies-literature
Project description:Peripheral nerve injuries occur as the result of sudden trauma and lead to reduced quality of life. The peripheral nervous system has an inherent capability to regenerate axons. However, peripheral nerve regeneration following injury is generally slow and incomplete that results in poor functional outcomes such as muscle atrophy. Although conventional surgical procedures for peripheral nerve injuries present many benefits, there are still several limitations including scarring, difficult accessibility to donor nerve, neuroma formation and a need to sacrifice the autologous nerve. For many years, other therapeutic approaches for peripheral nerve injuries have been explored, the most notable being the replacement of Schwann cells, the glial cells responsible for clearing out debris from the site of injury. Introducing cultured Schwann cells to the injured sites showed great benefits in promoting axonal regeneration and functional recovery. However, there are limited sources of Schwann cells for extraction and difficulties in culturing Schwann cells in vitro. Therefore, novel therapeutic avenues that offer maximum benefits for the treatment of peripheral nerve injuries should be investigated. This review focused on strategies using mesenchymal stem cells to promote peripheral nerve regeneration including exosomes of mesenchymal stem cells, nerve engineering using the nerve guidance conduits containing mesenchymal stem cells, and genetically engineered mesenchymal stem cells. We present the current progress of mesenchymal stem cell treatment of peripheral nerve injuries.
| S-EPMC8354135 | biostudies-literature
Project description:In vertebrates, the peripheral nervous system has retained its regenerative capacity, enabling severed axons to reconnect with their original synaptic targets. While it is well documented that a favorable environment is critical for nerve regeneration, the complex cellular interactions between injured nerves with cells in their environment, as well as the functional significance of these interactions, have not been determined in vivo and in real time. Here we provide the first minute-by-minute account of cellular interactions between laser transected motor nerves and macrophages in live intact zebrafish. We show that macrophages arrive at the lesion site long before axon fragmentation, much earlier than previously thought. Moreover, we find that axon fragmentation triggers macrophage invasion into the nerve to engulf axonal debris, and that delaying nerve fragmentation in a Wld(s) model does not alter macrophage recruitment but induces a previously unknown 'nerve scanning' behavior, suggesting that macrophage recruitment and subsequent nerve invasion are controlled by separate mechanisms. Finally, we demonstrate that macrophage recruitment, thought to be dependent on Schwann cell-derived signals, occurs independently of Schwann cells. Thus, live cell imaging defines novel cellular and functional interactions between injured nerves and immune cells.
| S-EPMC3324096 | biostudies-other
Project description:BackgroundClearance of myelin debris and remyelination of myelin are necessary steps for peripheral nerve remodeling and regeneration. It has yet to be clarified which genes or proteins are involved in endocytosis or exocytosis in the removal of myelin debris during peripheral nerve repair.MethodsFor this project, a rat model of subacute stage of sciatic nerve injury was established first. Subsequently, normal Schwann cells (NSCs) and activated Schwann cells (ASCs) were harvest before and after peripheral nerve injury (PNI). Following methylated DNA immunoprecipitation sequencing (MeDIP-seq) and tandem mass tags (TMT) labeling analysis of NSCs and ASCs, what common biomarkers changes in peripheral nervous systems remain to be elucidated.ResultsA total of 14,770 different expression genes (DEGs) and 3249 different expression proteins (DEPs) were screened between ASCs and NSCs. For the exosomes, the diameter and particles concentration of exosomes were 141.7 nm and 2.97 × 107 particles/mL, respectively. The size distribution of exosomes was 50-200 nm. ASCs showed higher cellular uptake ability than the NSCs by cellular uptake test. Moreover, RAB7A, ARF6, ARF1, VPS45, RAB11A, DNM3, and NEDD4 were the core markers and may control the molecular mechanism of the Endocytosis pathway.ConclusionThese biomarkers may play significant roles in the initiation phase of demyelination and axon regeneration.The translational potential of this articleThis study explores that the endocytosis-associated patterns of Schwann cells may be new therapeutic strategy for nerve tissue engineering and nerve regeneration.
| S-EPMC8551787 | biostudies-literature
Project description:PurposePeripheral nerve injury (PNI) is a known adverse event following upper-limb surgery performed under brachial plexus regional anesthesia (RA). When PNI is noted after surgery, patients and providers often have questions about which factors might have contributed to this complication. This systematic review evaluates the literature on hand and shoulder surgeries performed under ultrasound-guided, plexus RA to identify factors potentially associated with PNI, including the surgery location and block type. We hypothesized that shoulder surgery might be associated with an increased risk of PNI compared to hand surgery.MethodsA systematic review of the relevant literature was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Only prospective studies on the use of ultrasound-guided, preoperative, brachial plexus RA for hand or shoulder surgery on adult patients were included. Study groups were categorized according to surgery location and block type and compared across a number of factors via univariate and multivariate analyses.ResultsA total of 3,037 abstracts were screened; 192 full-text articles were independently reviewed by 2 of the authors; and 53 studies were included in the systematic review analysis. Following hand surgery, PNI was reported at an average rate of 1.35% ± 3.21% across 836 subjects in 40 study groups; after shoulder surgery, the average rate was 0.50% ± 1.57% across 3,383 subjects in 15 study groups. There was no statistically significant correlation between the incidence of PNI and surgery location (P =.70) or any of the most common approaches for brachial plexus anesthesia in the multivariate analysis.ConclusionsThis systematic review of over 50 articles on upper-limb surgery performed under RA shows no association between the incidence of PNI and the location of surgery or type of brachial plexus block.Type of study/level of evidenceDiagnostic II.
| S-EPMC9308165 | biostudies-literature
Project description:Peripheral nerves are important pathways for receiving afferent sensory impulses and sending out efferent motor instructions, as carried out by sensory nerve fibers and motor nerve fibers. It has remained a great challenge to functionally reconnect nerve internal fiber bundles (or fascicles) in nerve repair. One possible solution may be to establish a 3D nerve fascicle visualization system. This study described the key technology of 3D peripheral nerve fascicle reconstruction. Firstly, fixed nerve segments were embedded with position lines, cryostat-sectioned continuously, stained and imaged histologically. Position line cross-sections were identified using a trained support vector machine method, and the coordinates of their central pixels were obtained. Then, nerve section images were registered using the bilinear method, and edges of fascicles were extracted using an improved gradient vector flow snake method. Subsequently, fascicle types were identified automatically using the multi-directional gradient and second-order gradient method. Finally, a 3D virtual model of internal fascicles was obtained after section images were processed. This technique was successfully applied for 3D reconstruction for the median nerve of the hand-wrist and cubital fossa regions and the gastrocnemius nerve. This nerve internal fascicle 3D reconstruction technology would be helpful for aiding peripheral nerve repair and virtual surgery.
| S-EPMC4657002 | biostudies-other
Project description:Malignant peripheral nerve sheath tumor (MPNST) is the leading cause of mortality in patients with neurofibromatosis type 1. In 2002, an MPNST consensus statement reviewed the current knowledge and provided guidance for the diagnosis and management of MPNST. Although the improvement in clinical outcome has not changed, substantial progress has been made in understanding the natural history and biology of MPNST through imaging and genomic advances since 2002. Genetically engineered mouse models that develop MPNST spontaneously have greatly facilitated preclinical evaluation of novel drugs for translation into clinical trials led by consortia efforts. Continued work in identifying alterations that contribute to the transformation, progression, and metastasis of MPNST coupled with longitudinal follow-up, biobanking, and data sharing is needed to develop prognostic biomarkers and effective prevention and therapeutic strategies for MPNST.
| S-EPMC5448069 | biostudies-literature
Project description:ChIP-seq of H3K27acetylation in sham and injured nerve. Schwann cells play an important role in the response of peripheral nerve to injury. This study was designed to identify enhancers that are altered in sciatic nerve at 3 days post-injury to help identify pathways that mediate the gene expression reprogramming that occurs in Schwann cells after nerve injury. We employed ChIP-seq analysis of H3K27 acetylation as a mark of actively engaged enhancers, and compared enhancers in the distal stump of transected sciatic nerve compared to contralateral (sham) condition.
2014-12-15 | GSE63103 | GEO