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Stem Cells and Development Feb 2017Despite a substantially increased understanding of neuropathophysiology, insufficient functional recovery after peripheral nerve injury remains a significant clinical... (Review)
Review
Despite a substantially increased understanding of neuropathophysiology, insufficient functional recovery after peripheral nerve injury remains a significant clinical challenge. Nerve regeneration following injury is dependent on Schwann cells, the supporting cells in the peripheral nervous system. Following nerve injury, Schwann cells adopt a proregenerative phenotype, which supports and guides regenerating nerves. However, this phenotype may not persist long enough to ensure functional recovery. Tissue-engineered nerve repair devices containing therapeutic cells that maintain the appropriate phenotype may help enhance nerve regeneration. The combination of gene and cell therapy is an emerging experimental strategy that seeks to provide the optimal environment for axonal regeneration and reestablishment of functional circuits. This review aims to summarize current preclinical evidence with potential for future translation from bench to bedside.
Topics: Animals; Cellular Microenvironment; Genetic Therapy; Humans; Nerve Regeneration; Peripheral Nerves; Stem Cell Transplantation; Tissue Engineering
PubMed: 27960587
DOI: 10.1089/scd.2016.0188 -
The Journal of Veterinary Medical... Jul 2016A 9-year-old male mixed breed cat showed chronic progressive neurological symptoms, which are represented by ataxia and seizures. At necropsy, spinal roots and spinal...
A 9-year-old male mixed breed cat showed chronic progressive neurological symptoms, which are represented by ataxia and seizures. At necropsy, spinal roots and spinal ganglions at the level of sixth cervical nerve to second thoracic nerve were bilaterally swollen and replaced by white mass lesions. Right brachial plexus and cranial nerves (III, V and VII) were also swollen. A mass lesion was found in the right frontal lobe of the cerebrum. Histologically, neoplastic lymphocytes extensively involved the peripheral nerves, and they infiltrated into the cerebral and spinal parenchyma according to the peripheral nerve tract. Immunohistochemically, most neoplastic lymphocytes were positive for CD20. The clinical and histological features in this case resemble those of neurolymphomatosis in humans.
Topics: Animals; Brachial Plexus; Cat Diseases; Cats; Cranial Nerves; Frontal Lobe; Ganglia, Spinal; Male; Marek Disease; Spinal Nerve Roots
PubMed: 26960326
DOI: 10.1292/jvms.15-0553 -
The European Journal of Neuroscience Feb 2016The study of peripheral nerve repair and regeneration is particularly relevant in the light of the high clinical incidence of nerve lesions. However, the clinical... (Review)
Review
The study of peripheral nerve repair and regeneration is particularly relevant in the light of the high clinical incidence of nerve lesions. However, the clinical outcome after nerve lesions is often far from satisfactory and the functional recovery is almost never complete. Therefore, a number of therapeutic approaches are being investigated, ranging from local delivery of trophic factors and other molecules to bioactive biomaterials and complex nerve prostheses. Translation of the new therapeutic approaches to the patient always requires a final pre-clinical step using in vivo animal models. The need to limit as much as possible animal use in biomedical research, however, makes the preliminary use of in vitro models mandatory from an ethical point of view. In this article, the different types of in vitro models available today for the study of peripheral nerve regeneration have been ranked by adopting a three-step stair model based on their increasing ethical impact: (i) cell line-based models, which raise no ethical concern; (ii) primary cell-based models, which have low ethical impact as animal use, although necessary, is limited; and (iii) organotypic ex vivo-based models, which raise moderate ethical concerns as the use of laboratory animals is required although with much lower impact on animal wellbeing in comparison to in vivo models of peripheral nerve regeneration. This article aims to help researchers in selecting the best experimental approach for their scientific goals driven by the 'Three Rs' (3Rs) rules (Replacement, Reduction or Refinement of animal use in research) for scientific research.
Topics: Animals; Culture Techniques; Humans; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves
PubMed: 26309051
DOI: 10.1111/ejn.13054 -
British Journal of Hospital Medicine... Oct 2022Entrapment of peripheral nerves can occur as they travel through restrictive spaces. This nerve compression can result in a constellation of signs and symptoms, which...
Entrapment of peripheral nerves can occur as they travel through restrictive spaces. This nerve compression can result in a constellation of signs and symptoms, which are often called syndromes. Patients initially report pain, paraesthesia and numbness, followed by weakness and clumsiness and, ultimately, muscle wasting. The specific region of paraesthesia and pain and the specific muscle weakness is determined by the peripheral nerve involved and the location of the entrapment. Diagnosis is mainly based on history and examination. Further investigations are available for atypical presentations. Each syndrome has its own set of risk factors, but repetitive action and muscle overuse are commonly associated with most syndromes. The treatment is activity modification followed by steroid injection and finally surgical decompression for ongoing persistent symptoms or severe initial presentation. This article outlines the history, examination, possible investigations and management for common peripheral nerve entrapments of the median, ulnar and radial nerves.
Topics: Humans; Ulnar Nerve; Paresthesia; Nerve Compression Syndromes; Upper Extremity; Pain
PubMed: 36322444
DOI: 10.12968/hmed.2022.0111 -
Experimental Neurology Aug 2022Neurons of the peripheral nervous system retain the intrinsic capability of regenerate their axons after injury, by triggering a complex activation response. This... (Review)
Review
Neurons of the peripheral nervous system retain the intrinsic capability of regenerate their axons after injury, by triggering a complex activation response. This genetic switch is dependent of signals from the injured axon. Schwann cells (SCs) in the distal stump of an injured nerve also play an active role in the local regulation of axonal programs, by using cell-to-cell contacts but also secreted signals, the so-called secretome. Secretome contains all the proteins (cytokines, growth factors and others) secreted by the cell and includes extracellular vesicles. The released vesicles can transport signaling proteins and both coding and regulatory RNAs, thus facilitating multilevel communication. It is nowadays clear that secretome of SCs is fundamental to both orchestrate Wallerian degeneration and to sustain axonal regeneration. Therefore, the use of secretome has emerged as an alternative to cell therapy in the field of tissue regeneration. In fact, separate components of SC secretome have been extensively used in experimental models to enhance peripheral nerve regeneration after injury. However, the most used secretome in neural therapies has been the one derived from mesenchymal (MSC) or other derived stem cells. In fact, the effects of cell therapy with MSCs have been mainly associated with the secretion of bioactive molecules and extracellular vesicles, which constitute their secretome. In this review, we first describe the role of SC and macrophage secretomes on Wallerian degeneration and axonal regeneration after peripheral nerve injury. Then, we review the different works reported in the literature that have used secretomes of SCs or MSCs in the treatment of peripheral nerve injuries in experimental models, to highlight the use of secretomes as a promising cell-free therapeutic approach, that reduces some of the risks associated with the use of cells, such as tumor formation or rejection.
Topics: Humans; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Schwann Cells; Secretome; Wallerian Degeneration
PubMed: 35398149
DOI: 10.1016/j.expneurol.2022.114069 -
International Journal of Molecular... Jan 2023Regeneration of damaged peripheral nerves remains one of the main challenges of neurosurgery and regenerative medicine, a nerve functionality is rarely restored,... (Review)
Review
Regeneration of damaged peripheral nerves remains one of the main challenges of neurosurgery and regenerative medicine, a nerve functionality is rarely restored, especially after severe injuries. Researchers are constantly looking for innovative strategies for tackling this problem, with the development of advanced tissue-engineered nerve conduits and new pharmacological and physical interventions, with the aim of improving patients' life quality. Different evaluation methods can be used to study the effectiveness of a new treatment, including functional tests, morphological assessment of regenerated nerve fibers and biomolecular analyses of key factors necessary for good regeneration. The number and diversity of protocols and methods, as well as the availability of innovative technologies which are used to assess nerve regeneration after experimental interventions, often makes it difficult to compare results obtained in different labs. The purpose of the current review is to describe the main morphological approaches used to evaluate the degree of nerve fiber regeneration in terms of their usefulness and limitations.
Topics: Humans; Peripheral Nerve Injuries; Peripheral Nerves; Nerve Fibers; Tissue Engineering; Nerve Regeneration; Sciatic Nerve
PubMed: 36768142
DOI: 10.3390/ijms24031818 -
Muscle & Nerve May 2022Sonographic alterations of peripheral nerves in pre-dialytic kidney disease are yet to be determined. We aimed to assess peripheral nerve cross-sectional area (CSA) and...
INTRODUCTION/AIMS
Sonographic alterations of peripheral nerves in pre-dialytic kidney disease are yet to be determined. We aimed to assess peripheral nerve cross-sectional area (CSA) and intraneural blood flow in patients with pre-dialytic chronic kidney disease (CKD) and diabetic kidney disease (DKD).
METHODS
Subjects with CKD (n = 20) or DKD (n = 20) underwent ultrasound to assess CSA of the median and tibial nerves as well as intraneural blood flow of the median nerve. Blood flow was quantified using maximum perfusion intensity. Neuropathy was assessed using the Total Neuropathy Score. A 6-m timed walk test was also performed. Healthy controls (n = 28) were recruited for comparison.
RESULTS
The DKD group had more severe neuropathy (p = .024), larger tibial nerve CSA (p = .002) and greater median nerve blood flow than the CKD group (p = .023). Blood flow correlated with serum potassium in disease groups (r = 0.652, p = .022). Disease groups had larger tibial nerve CSA than controls (p < .05). No blood flow was detected in controls. Tibial nerve enlargement was associated with slower maximal walking speeds in disease groups (r = -0.389, p = .021).
DISCUSSION
Subjects with DKD demonstrated enlarged tibial nerve CSA and increased median nerve blood flow compared to those with CKD. Elevations in serum potassium were associated with increased blood flow. Sonographic alterations were detectable in pre-dialytic kidney disease compared to controls, highlighting the utility of ultrasound in the assessment of nerve pathology in these patient groups.
Topics: Diabetes Mellitus; Female; Humans; Male; Peripheral Nerves; Potassium; Renal Insufficiency, Chronic; Tibial Nerve; Ultrasonography
PubMed: 35119701
DOI: 10.1002/mus.27513 -
Radiology Mar 2021With surging numbers of patients with coronavirus disease 2019 (COVID-19) throughout the world, neuromuscular complications and rehabilitation concerns are becoming more... (Review)
Review
With surging numbers of patients with coronavirus disease 2019 (COVID-19) throughout the world, neuromuscular complications and rehabilitation concerns are becoming more apparent. Peripheral nerve injury can occur in patients with COVID-19 secondary to postinfectious inflammatory neuropathy, prone positioning-related stretch and/or compression injury, systemic neuropathy, or nerve entrapment from hematoma. Imaging of peripheral nerves in patients with COVID-19 may help to characterize nerve abnormality, to identify site and severity of nerve damage, and to potentially elucidate mechanisms of injury, thereby aiding the medical diagnosis and decision-making process. This review article aims to provide a first comprehensive summary of the current knowledge of COVID-19 and peripheral nerve imaging.
Topics: COVID-19; Diagnosis, Differential; Diagnostic Imaging; Humans; Patient Positioning; Peripheral Nerve Injuries; Peripheral Nerves; SARS-CoV-2
PubMed: 33258748
DOI: 10.1148/radiol.2020203116 -
International Journal of Molecular... Mar 2024With the development of single-cell sequencing technology, the cellular composition of more and more tissues is being elucidated. As the whole nervous system has been... (Review)
Review
With the development of single-cell sequencing technology, the cellular composition of more and more tissues is being elucidated. As the whole nervous system has been extensively studied, the cellular composition of the peripheral nerve has gradually been revealed. By summarizing the current sequencing data, we compile the heterogeneities of cells that have been reported in the peripheral nerves, mainly the sciatic nerve. The cellular variability of Schwann cells, fibroblasts, immune cells, and endothelial cells during development and disease has been discussed in this review. The discovery of the architecture of peripheral nerves after injury benefits the understanding of cellular complexity in the nervous system, as well as the construction of tissue engineering nerves for nerve repair and axon regeneration.
Topics: Humans; Axons; Endothelial Cells; Nerve Regeneration; Schwann Cells; Sciatic Nerve; Peripheral Nerve Injuries
PubMed: 38542483
DOI: 10.3390/ijms25063511 -
Neural Plasticity 2022Peripheral nerve injury can lead to partial or complete loss of limb function, and nerve transfer is an effective surgical salvage for patients with these injuries. The... (Review)
Review
Peripheral nerve injury can lead to partial or complete loss of limb function, and nerve transfer is an effective surgical salvage for patients with these injuries. The inability of deprived cortical regions representing damaged nerves to overcome corresponding maladaptive plasticity after the reinnervation of muscle fibers and sensory receptors is thought to be correlated with lasting and unfavorable functional recovery. However, the concept of central nervous system plasticity is rarely elucidated in classical textbooks involving peripheral nerve injury, let alone peripheral nerve transfer. This article is aimed at providing a comprehensive understanding of central nervous system plasticity involving peripheral nerve injury by reviewing studies mainly in human or nonhuman primate and by highlighting the functional and structural modifications in the central nervous system after peripheral nerve transfer. Hopefully, it will help surgeons perform successful nerve transfer under the guidance of modern concepts in neuroplasticity.
Topics: Animals; Central Nervous System; Humans; Nerve Regeneration; Nerve Transfer; Neuronal Plasticity; Peripheral Nerve Injuries; Peripheral Nerves
PubMed: 35342394
DOI: 10.1155/2022/5345269