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Anatomical Record (Hoboken, N.J. : 2007) Oct 2018Injuries to the peripheral nerves result in loss of motor, sensory and autonomic functions in the denervated segments of the body, thus having strong impact in the...
Injuries to the peripheral nerves result in loss of motor, sensory and autonomic functions in the denervated segments of the body, thus having strong impact in the quality of life of affected patients. Neurons are able to regenerate their injured axons in the peripheral nerves; however, the endogenous repair mechanisms usually do not allow for a satisfactory functional recovery, especially after severe nerve injuries. The interest on regeneration after peripheral nerve injuries has increased in the recent years due to the numerous advances derived from studies of neurobiology, cell therapy, and tissue engineering. This Thematic Papers Issue brings together a number of papers, authored by researchers in the field, which cover a wide spectrum of topics related to regeneration and repair of peripheral nerve injuries. The Issue proposal originated from the recent 4th International Symposium on Peripheral Nerve Regeneration (ISPNR2017) which was hosted by Xavier Navarro and the European Society for the Study of Peripheral Nerve Repair and Regeneration in Barcelona, Spain. Anat Rec, 301:1614-1617, 2018. © 2018 Wiley Periodicals, Inc.
Topics: Animals; Humans; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves
PubMed: 30299596
DOI: 10.1002/ar.23941 -
Tremor and Other Hyperkinetic Movements... 2022There is growing recognition of peripheral stimulation techniques for controlling arm symptoms in essential tremor (ET). Recently, the FDA gave clearance to the Cala... (Review)
Review
BACKGROUND
There is growing recognition of peripheral stimulation techniques for controlling arm symptoms in essential tremor (ET). Recently, the FDA gave clearance to the Cala system, a device worn around the wrist to treat arm tremors. The Cala system stimulates the sensory afferents of the peripheral nerves with high-frequency pulses. These pulses are delivered to the median and radial nerves alternately at the tremor frequency of the individual patient.
METHODS
The PubMed database was searched using the terms ("Essential Tremor"[Mesh] OR "essential tremor" [Title/Abstract] OR "tremor" [Title/Abstract]) AND ("peripheral arm stimulation" [Title/Abstract] OR "Cala device" [Title/Abstract] OR "sensory afferent stimulation" [Title/Abstract] OR "afferent stimulation" [Title/Abstract] OR "arm stimulation" [Title/Abstract] OR "peripheral nerve stimulation" [Title/Abstract]).
RESULTS
The search yielded 54 articles. Many studies discussed the rationale and various strategies for peripheral modulation of tremor. While the Cala system was found to be safe and well-tolerated in ET, data on efficacy revealed mixed findings. In a large randomized, blinded trial (n = 77), the primary outcome evaluated with spiral drawing task did not improve but the secondary outcomes reflected by the arm tremor severity and the activities of the daily living score revealed 20-25% improvements. A subsequent trial (n = 323) found that the in-home use of the Cala device led to improvements of similar magnitude lasting for at least three months but the clinical assessments were open-labeled.
DISCUSSION
Peripheral stimulation techniques are promising therapeutic modalities for treating ET symptoms. Stimulation of sensory afferent nerve fibers at the wrist can potentially modulate the peripheral and central components of the tremor network. Although the Cala system is user-friendly, safe, and well-tolerated, the current clinical evidence on the efficacy is inconsistent and insufficient. Thus, more data is warranted for implementing peripheral nerve stimulation as a standard of care for ET.
HIGHLIGHTS
The current review discusses the rationale, background, and potential mechanisms for using peripheral arm stimulation devices for treating ET. The Cala system is a wrist-worn peripheral nerve stimulation device that received FDA clearance to treat arm tremors. The current review evaluates the evidence for the safety and efficacy of using the Cala system and similar devices in clinical practice.
Topics: Essential Tremor; Humans; Peripheral Nerves; Radial Nerve; Transcutaneous Electric Nerve Stimulation; Tremor
PubMed: 35949227
DOI: 10.5334/tohm.685 -
Neuron Oct 2020The development of new tools to interface with the nervous system, empowered by advances in electronics and materials science, has transformed neuroscience and is... (Review)
Review
The development of new tools to interface with the nervous system, empowered by advances in electronics and materials science, has transformed neuroscience and is informing therapies for neurological and mental conditions. Although the vast majority of neural engineering research has focused on advancing tools to study the brain, understanding the peripheral nervous system and other organs can similarly benefit from these technologies. To realize this vision, the neural interface technologies need to address the biophysical, mechanical, and chemical challenges posed by the peripheral nerves and organs. In this Perspective, we discuss design considerations and recent technological advances to modulate electrical signaling outside the central nervous system. The innovations in bioelectronics borne out of interdisciplinary collaborations between biologists and physical scientists may not only advance fundamental study of peripheral (neuro)physiology but also empower clinical interventions for conditions including neurological, gastrointestinal, and immune dysfunction.
Topics: Animals; Electric Stimulation; Electrodes, Implanted; Humans; Man-Machine Systems; Nanotechnology; Neurosciences; Optogenetics; Peripheral Nerves; Peripheral Nervous System; Telemetry
PubMed: 33120023
DOI: 10.1016/j.neuron.2020.09.025 -
Ugeskrift For Laeger Sep 2022The use of peripheral nerve blocks carries a small risk of most often temporary direct damage to the peripheral nerves. Due to lack of research and differing opinions... (Review)
Review
The use of peripheral nerve blocks carries a small risk of most often temporary direct damage to the peripheral nerves. Due to lack of research and differing opinions regarding the potential of nerve blocks delaying the diagnosis of acute compartment syndrome, there is currently no consensus between anaesthetic- and orthopaedic associations regarding the use of peripheral nerve blocks in patients at risk of acute compartment syndrome. More interdisciplinary research is needed to inform and promote an evidence-based discussion of the subject, as argued in this review.
Topics: Anesthesia, Conduction; Compartment Syndromes; Humans; Nerve Block; Peripheral Nerves
PubMed: 36205160
DOI: No ID Found -
Wiener Medizinische Wochenschrift (1946) Jun 2019Artificial and non-artificial nerve grafts are the gold standard in peripheral nerve reconstruction in cases with extensive loss of nerve tissue, particularly where... (Review)
Review
Artificial and non-artificial nerve grafts are the gold standard in peripheral nerve reconstruction in cases with extensive loss of nerve tissue, particularly where a direct end-to-end suture or an autologous nerve graft is inauspicious. Different materials are marketed and approved by the US Food and Drug Administration (FDA) for peripheral nerve graft reconstruction. The most frequently used materials are collagen and poly(DL-lactide-ε-caprolactone). Only one human nerve allograft is listed for peripheral nerve reconstruction by the FDA. All marketed nerve grafts are able to demonstrate sufficient nerve regeneration over small distances not exceeding 3.0 cm. A key question in the field is whether nerve reconstruction on large defect lengths extending 4.0 cm or more is possible. This review gives a summary of current clinical and experimental approaches in peripheral nerve surgery using artificial and non-artificial nerve grafts in short and long distance nerve defects. Strategies to extend nerve graft lengths for long nerve defects, such as enhancing axonal regeneration, include the additional application of Schwann cells, mesenchymal stem cells or supporting co-factors like growth factors on defect sizes between 4.0 and 8.0 cm.
Topics: Humans; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Schwann Cells; Transplantation, Homologous; United States
PubMed: 30547373
DOI: 10.1007/s10354-018-0675-6 -
Plastic and Reconstructive Surgery Sep 2023Nerve transection is the most common form of peripheral nerve injury. Treatment of peripheral nerve injury has primarily focused on stabilization and mechanical cues to...
BACKGROUND
Nerve transection is the most common form of peripheral nerve injury. Treatment of peripheral nerve injury has primarily focused on stabilization and mechanical cues to guide extension of the regenerating growth cone across the site of transection. The authors investigated the effects of a peripheral nerve matrix (PNM) hydrogel on recovery after nerve transection.
METHODS
The authors used rodent models to determine the effect of PNM on axon extension, electrophysiologic nerve conduction, force generation, and neuromuscular junction formation after nerve transection and repair. The authors complemented this work with in vivo and in vitro fluorescence-activated cell sorting and immunohistochemistry approaches to determine the effects of PNM on critical cell populations early after repair.
RESULTS
Extension of axons from the proximal stump and overall green fluorescent protein-positive axon volume within the regenerative bridge were increased in the presence of PNM compared with an empty conduit ( P < 0.005) 21 days after repair. PNM increased electrophysiologic conduction (compound muscle action potential amplitude) across the repair site ( P < 0.05) and neuromuscular junction formation ( P = 0.04) 56 days after repair. PNM produced a shift in macrophage phenotype in vitro and in vivo ( P < 0.05) and promoted regeneration in a murine model used to characterize the early immune response to PNM ( P < 0.05).
CONCLUSION
PNM, delivered by subepineural injection, promoted recovery after nerve transection with immediate repair, supporting a beneficial macrophage response, axon extension, and downstream remodeling using a range of clinically relevant outcome measures.
CLINICAL RELEVANCE STATEMENT
This article describes an approach for subepineural injection at the site of nerve coaptation to modulate the response to injury and improve outcomes.
Topics: Mice; Animals; Peripheral Nerve Injuries; Hydrogels; Peripheral Nerves; Axons; Neural Conduction; Nerve Regeneration
PubMed: 36946873
DOI: 10.1097/PRS.0000000000010261 -
International Journal of Molecular... May 2023In peripheral nerve injuries (PNI) with substance loss, where tensionless end-to-end suture is not achievable, the positioning of a graft is required. Available options... (Review)
Review
In peripheral nerve injuries (PNI) with substance loss, where tensionless end-to-end suture is not achievable, the positioning of a graft is required. Available options include autografts (e.g., sural nerve, medial and lateral antebrachial cutaneous nerves, superficial branch of the radial nerve), allografts (Avance; human origin), and hollow nerve conduits. There are eleven commercial hollow conduits approved for clinical, and they consist of devices made of a non-biodegradable synthetic polymer (polyvinyl alcohol), biodegradable synthetic polymers (poly(DL-lactide-ε-caprolactone); polyglycolic acid), and biodegradable natural polymers (collagen type I with/without glycosaminoglycan; chitosan; porcine small intestinal submucosa); different resorption times are available for resorbable guides, ranging from three months to four years. Unfortunately, anatomical/functional nerve regeneration requirements are not satisfied by any of the possible alternatives; to date, focusing on wall and/or inner lumen organization/functionalization seems to be the most promising strategy for next-generation device fabrication. Porous or grooved walls as well as multichannel lumens and luminal fillers are the most intriguing options, eventually also including the addition of cells (Schwann cells, bone marrow-derived, and adipose tissue derived stem cells) to support nerve regeneration. This review aims to describe common alternatives for severe PNI recovery with a highlight of future conduits.
Topics: Animals; Humans; Swine; Sciatic Nerve; Polyesters; Peripheral Nerves; Prostheses and Implants; Peripheral Nerve Injuries; Polyglycolic Acid; Nerve Regeneration
PubMed: 37298122
DOI: 10.3390/ijms24119170 -
International Journal of Molecular... Sep 2016Peripheral nerve injuries remain a significant source of long lasting morbidity, disability, and economic costs. Much research continues to be performed in areas related... (Review)
Review
Peripheral nerve injuries remain a significant source of long lasting morbidity, disability, and economic costs. Much research continues to be performed in areas related to improving the surgical outcomes of peripheral nerve repair. In this review, the physiology of peripheral nerve regeneration and the multitude of efforts to improve surgical outcomes are discussed. Improvements in tissue engineering that have allowed for the use of synthetic conduits seeded with neurotrophic factors are highlighted. Selected pre-clinical and available clinical data using cell based methods such as Schwann cell, undifferentiated, and differentiated stem cell transplantation to guide and enhance peripheral nerve regeneration are presented. The limitations that still exist in the utility of neurotrophic factors and cell-based therapies are outlined. Strategies that are most promising for translation into the clinical arena are suggested.
Topics: Animals; Forecasting; Humans; Nerve Regeneration; Neural Stem Cells; Peripheral Nerve Injuries; Peripheral Nerves; Schwann Cells; Stem Cell Transplantation; Tissue Engineering
PubMed: 27618010
DOI: 10.3390/ijms17091494 -
Journal of Neuroinflammation Nov 2023Although peripheral nerves have an intrinsic self-repair capacity following damage, functional recovery is limited in patients. It is a well-established fact that...
BACKGROUND
Although peripheral nerves have an intrinsic self-repair capacity following damage, functional recovery is limited in patients. It is a well-established fact that macrophages accumulate at the site of injury. Numerous studies indicate that the phenotypic shift from M1 macrophage to M2 macrophage plays a crucial role in the process of axon regeneration. This polarity change is observed exclusively in peripheral macrophages but not in microglia and CNS macrophages. However, the molecular basis of axonal regeneration by M2 macrophage is not yet fully understood. Herein, we aimed to identify the M2 macrophage-derived axon regeneration factor.
METHODS
We established a peripheral nerve injury model by transection of the inferior alveolar nerve (IANX) in Sprague-Dawley rats. Transcriptome analysis was performed on the injured nerve. Recovery from sensory deficits in the mandibular region and histological reconnection of IAN after IANX were assessed in rats with macrophage depletion by clodronate. We investigated the effects of adoptive transfer of M2 macrophages or M2-derived cathepsin S (CTSS) on the sensory deficit. CTSS initiating signaling was explored by western blot analysis in IANX rats and immunohistochemistry in co-culture of primary fibroblasts and Schwann cells (SCs).
RESULTS
Transcriptome analysis revealed that CTSS, a macrophage-selective lysosomal protease, was upregulated in the IAN after its injury. Spontaneous but partial recovery from a sensory deficit in the mandibular region after IANX was abrogated by macrophage ablation at the injured site. In addition, a robust induction of c-Jun, a marker of the repair-supportive phenotype of SCs, after IANX was abolished by macrophage ablation. As in transcriptome analysis, CTSS was upregulated at the injured IAN than in the intact IAN. Endogenous recovery from hypoesthesia was facilitated by supplementation of CTSS but delayed by pharmacological inhibition or genetic silencing of CTSS at the injured site. Adoptive transfer of M2-polarized macrophages at this site facilitated sensory recovery dependent on CTSS in macrophages. Post-IANX, CTSS caused the cleavage of Ephrin-B2 in fibroblasts, which, in turn, bound EphB2 in SCs. CTSS-induced Ephrin-B2 cleavage was also observed in human sensory nerves. Inhibition of CTSS-induced Ephrin-B2 signaling suppressed c-Jun induction in SCs and sensory recovery.
CONCLUSIONS
These results suggest that M2 macrophage-derived CTSS contributes to axon regeneration by activating SCs via Ephrin-B2 shedding from fibroblasts.
Topics: Animals; Humans; Rats; Axons; Cathepsins; Ephrin-B2; Fibroblasts; Macrophages; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Rats, Sprague-Dawley; Schwann Cells
PubMed: 37946211
DOI: 10.1186/s12974-023-02943-2 -
Anatomical Record (Hoboken, N.J. : 2007) Oct 2018Vascularization plays a significant role in treating nerve injury, especially to avoid the central necrosis observed in nerve grafts for large and long nerve defects. It... (Review)
Review
Vascularization plays a significant role in treating nerve injury, especially to avoid the central necrosis observed in nerve grafts for large and long nerve defects. It is known that sufficient vascularization can sustain cell survival and maintain cell integration within tissue-engineered constructs. Several studies have also shown that vascularization affects nerve regeneration. Motivated by these studies, vascularized nerve grafts have been developed using various different techniques, although donor site morbidity and limited nerve supply remain significant drawbacks. Tissue engineering provides an exciting alternative approach to prefabricate vascularized nerve constructs which could overcome the limitations of grafts. In this review article, we focus on the role of vascularization in nerve regeneration, discussing various approaches to generate vascularized nerve constructs and the contribution of tissue engineering and mathematical modeling to aid in developing vascularized engineered nerve constructs, illustrating these aspects with examples from our research experience. Anat Rec, 301:1657-1667, 2018. © 2018 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.
Topics: Animals; Endothelial Cells; Humans; Neovascularization, Physiologic; Nerve Regeneration; Nerve Transfer; Peripheral Nerves; Tissue Engineering; Transplants
PubMed: 30334363
DOI: 10.1002/ar.23919