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International Journal of Molecular... Nov 2020Injured peripheral nerves but not central nerves have the capacity to regenerate and reinnervate their target organs. After the two most severe peripheral nerve injuries... (Review)
Review
Injured peripheral nerves but not central nerves have the capacity to regenerate and reinnervate their target organs. After the two most severe peripheral nerve injuries of six types, crush and transection injuries, nerve fibers distal to the injury site undergo Wallerian degeneration. The denervated Schwann cells (SCs) proliferate, elongate and line the endoneurial tubes to guide and support regenerating axons. The axons emerge from the stump of the viable nerve attached to the neuronal soma. The SCs downregulate myelin-associated genes and concurrently, upregulate growth-associated genes that include neurotrophic factors as do the injured neurons. However, the gene expression is transient and progressively fails to support axon regeneration within the SC-containing endoneurial tubes. Moreover, despite some preference of regenerating motor and sensory axons to "find" their appropriate pathways, the axons fail to enter their original endoneurial tubes and to reinnervate original target organs, obstacles to functional recovery that confront nerve surgeons. Several surgical manipulations in clinical use, including nerve and tendon transfers, the potential for brief low-frequency electrical stimulation proximal to nerve repair, and local FK506 application to accelerate axon outgrowth, are encouraging as is the continuing research to elucidate the molecular basis of nerve regeneration.
Topics: Animals; Axons; Humans; Muscle, Skeletal; Nerve Regeneration; Neurogenesis; Peripheral Nerve Injuries; Peripheral Nerves; Recovery of Function; Schwann Cells; Tacrolimus
PubMed: 33212795
DOI: 10.3390/ijms21228652 -
International Journal of Molecular... Jan 2022Peripheral nerve injuries (PNI) can have several etiologies, such as trauma and iatrogenic interventions, that can lead to the loss of structure and/or function... (Review)
Review
Peripheral nerve injuries (PNI) can have several etiologies, such as trauma and iatrogenic interventions, that can lead to the loss of structure and/or function impairment. These changes can cause partial or complete loss of motor and sensory functions, physical disability, and neuropathic pain, which in turn can affect the quality of life. This review aims to revisit the concepts associated with the PNI and the anatomy of the peripheral nerve is detailed to explain the different types of injury. Then, some of the available therapeutic strategies are explained, including surgical methods, pharmacological therapies, and the use of cell-based therapies alone or in combination with biomaterials in the form of tube guides. Nevertheless, even with the various available treatments, it is difficult to achieve a perfect outcome with complete functional recovery. This review aims to enhance the importance of new therapies, especially in severe lesions, to overcome limitations and achieve better outcomes. The urge for new approaches and the understanding of the different methods to evaluate nerve regeneration is fundamental from a One Health perspective. In vitro models followed by in vivo models are very important to be able to translate the achievements to human medicine.
Topics: Animals; Biomarkers; Clinical Studies as Topic; Combined Modality Therapy; Disease Management; Disease Models, Animal; Disease Susceptibility; Humans; Peripheral Nerve Injuries; Peripheral Nerves; Treatment Outcome
PubMed: 35055104
DOI: 10.3390/ijms23020918 -
Neurology India 2019Peripheral nerve injuries are a heterogeneous and distinct group of disorders that are secondary to various causes commonly including motor vehicle accidents, falls,... (Review)
Review
Peripheral nerve injuries are a heterogeneous and distinct group of disorders that are secondary to various causes commonly including motor vehicle accidents, falls, industrial accidents, household accidents, and penetrating trauma. The earliest classification of nerve injuries was given by Seddon and Sunderland, which holds true till date and is commonly used. Neuropraxia, axonotmesis, and neurotmesis are the three main types of nerve injuries. The electrophysiological studies including nerve conduction studies (NCS) and electromyography (EMG) play a key role and are now considered an extension of the clinical examination in patients with peripheral nerve injuries. The electrophysiological results should be interpreted in the light of clinical examination. These studies help in localizing the site of lesion, determine the type and severity of lesion, and help in prognosticating. In neuropraxia, the compound muscle action potential (CMAP) and sensory nerve action potential (SNAP) are elicitable on stimulating the nerve distal to the site of the lesion but demonstrate conduction block on proximal stimulation. The electrodiagnostic findings in axonotmesis and neurotmesis are similar. After few days of injury, Wallerian degeneration sets in with failure to record CMAP and SNAP. Intraoperative technique involves recording from the peripheral nerves during the intraoperative period and has proved useful in the surgical management of nerve injuries and helps in identifying the injured nerve, to determine whether the nerve is in continuity and in localizing the site of lesion. Intraoperative monitoring also helps in identifying the nerve close to an ongoing surgery so that surgical damage to the nerve can be prevented.
Topics: Action Potentials; Electrodiagnosis; Electromyography; Humans; Intraoperative Neurophysiological Monitoring; Neural Conduction; Neurosurgical Procedures; Peripheral Nerve Injuries; Peripheral Nerves; Prognosis
PubMed: 31857526
DOI: 10.4103/0028-3886.273626 -
Biomolecules Dec 2022Peripheral nerve injuries (PNI) are common and often result in lifelong disability. The peripheral nervous system has an inherent ability to regenerate following injury,... (Review)
Review
Peripheral nerve injuries (PNI) are common and often result in lifelong disability. The peripheral nervous system has an inherent ability to regenerate following injury, yet complete functional recovery is rare. Despite advances in the diagnosis and repair of PNIs, many patients suffer from chronic pain, and sensory and motor dysfunction. One promising surgical adjunct is the application of intraoperative electrical stimulation (ES) to peripheral nerves. ES acts through second messenger cyclic AMP to augment the intrinsic molecular pathways of regeneration. Decades of animal studies have demonstrated that 20 Hz ES delivered post-surgically accelerates axonal outgrowth and end organ reinnervation. This work has been translated clinically in a series of randomized clinical trials, which suggest that ES can be used as an efficacious therapy to improve patient outcomes following PNIs. The aim of this review is to discuss the cellular physiology and the limitations of regeneration after peripheral nerve injuries. The proposed mechanisms of ES protocols and how they facilitate nerve regeneration depending on timing of administration are outlined. Finally, future directions of research that may provide new perspectives on the optimal delivery of ES following PNI are discussed.
Topics: Animals; Peripheral Nerve Injuries; Axons; Peripheral Nerves; Nerve Regeneration; Electric Stimulation
PubMed: 36551285
DOI: 10.3390/biom12121856 -
Neurobiology of Disease Jan 2023The glial cell of the peripheral nervous system (PNS), the Schwann cell (SC), counts among the most multifaceted cells of the body. During development, SCs secure... (Review)
Review
The glial cell of the peripheral nervous system (PNS), the Schwann cell (SC), counts among the most multifaceted cells of the body. During development, SCs secure neuronal survival and participate in axonal path finding. Simultaneously, they orchestrate the architectural set up of the developing nerves, including the blood vessels and the endo-, peri- and epineurial layers. Perinatally, in rodents, SCs radially sort and subsequently myelinate individual axons larger than 1 μm in diameter, while small calibre axons become organised in non-myelinating Remak bundles. SCs have a vital role in maintaining axonal health throughout life and several specialized SC types perform essential functions at specific locations, such as terminal SC at the neuromuscular junction (NMJ) or SC within cutaneous sensory end organs. In addition, neural crest derived satellite glia maintain a tight communication with the soma of sensory, sympathetic, and parasympathetic neurons and neural crest derivatives are furthermore an indispensable part of the enteric nervous system. The remarkable plasticity of SCs becomes evident in the context of a nerve injury, where SC transdifferentiate into intriguing repair cells, which orchestrate a regenerative response that promotes nerve repair. Indeed, the multiple adaptations of SCs are captivating, but remain often ill-resolved on the molecular level. Here, we summarize and discuss the knowns and unknowns of the vast array of functions that this single cell type can cover in peripheral nervous system development, maintenance, and repair.
Topics: Humans; Schwann Cells; Peripheral Nerves; Axons; Neurons; Peripheral Nervous System; Nerve Regeneration; Peripheral Nerve Injuries
PubMed: 36493976
DOI: 10.1016/j.nbd.2022.105952 -
Cell Metabolism Dec 2023The peripheral nervous system harbors a remarkable potential to regenerate after acute nerve trauma. Full functional recovery, however, is rare and critically depends on...
The peripheral nervous system harbors a remarkable potential to regenerate after acute nerve trauma. Full functional recovery, however, is rare and critically depends on peripheral nerve Schwann cells that orchestrate breakdown and resynthesis of myelin and, at the same time, support axonal regrowth. How Schwann cells meet the high metabolic demand required for nerve repair remains poorly understood. We here report that nerve injury induces adipocyte to glial signaling and identify the adipokine leptin as an upstream regulator of glial metabolic adaptation in regeneration. Signal integration by leptin receptors in Schwann cells ensures efficient peripheral nerve repair by adjusting injury-specific catabolic processes in regenerating nerves, including myelin autophagy and mitochondrial respiration. Our findings propose a model according to which acute nerve injury triggers a therapeutically targetable intercellular crosstalk that modulates glial metabolism to provide sufficient energy for successful nerve repair.
Topics: Peripheral Nerves; Myelin Sheath; Neuroglia; Schwann Cells; Nerve Regeneration
PubMed: 37989315
DOI: 10.1016/j.cmet.2023.10.017 -
Physiology (Bethesda, Md.) Nov 2022Peripheral nerve injuries often result in life-altering functional deficits even with optimal management. Unlike the central nervous system, peripheral nerves have the... (Review)
Review
Peripheral nerve injuries often result in life-altering functional deficits even with optimal management. Unlike the central nervous system, peripheral nerves have the ability to regenerate lost axons after injury; however, axonal regeneration does not equate to full restoration of function. To overcome this physiological shortcoming, advances in nerve regeneration and repair are paramount, including electrical stimulation, gene therapy, and surgical technique advancements.
Topics: Axons; Electric Stimulation; Genetic Therapy; Humans; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves
PubMed: 35820181
DOI: 10.1152/physiol.00008.2022 -
Cold Spring Harbor Perspectives in... May 2015Schwann cells develop from the neural crest in a well-defined sequence of events. This involves the formation of the Schwann cell precursor and immature Schwann cells,... (Review)
Review
Schwann cells develop from the neural crest in a well-defined sequence of events. This involves the formation of the Schwann cell precursor and immature Schwann cells, followed by the generation of the myelin and nonmyelin (Remak) cells of mature nerves. This review describes the signals that control the embryonic phase of this process and the organogenesis of peripheral nerves. We also discuss the phenotypic plasticity retained by mature Schwann cells, and explain why this unusual feature is central to the striking regenerative potential of the peripheral nervous system (PNS).
Topics: Animals; Cell Proliferation; Mice; Models, Biological; Nerve Regeneration; Neural Crest; Peripheral Nerves; Rats; Schwann Cells
PubMed: 25957303
DOI: 10.1101/cshperspect.a020487 -
Minerva Anestesiologica Jul 2019Pain is the most common complaint amongst trauma patients throughout the perioperative period. Multimodal analgesia is currently being regarded the mainstay, with... (Review)
Review
Pain is the most common complaint amongst trauma patients throughout the perioperative period. Multimodal analgesia is currently being regarded the mainstay, with regional anesthesia techniques constituting an integral part of it. Ultrasound imaging techniques display a plethora of advantages that have pervaded regional anesthesia practice. In this review, we set out to provide several examples of injuries, to elucidate the precise anatomy of fractured bones (osteotomes), and to elaborate on certain peripheral nerve blocks employed in pain management of trauma patients. Controversies/special considerations pertaining to peripheral nerve blocks also dictate thorough analysis: as such, acute compartment syndrome, acute peripheral nerve injuries, regional anesthesia in awake or anesthetized patients, continuous peripheral nerve blocks, positioning limitations and, finally, ultrasound imaging versus neurostimulation techniques are extensively reviewed.
Topics: Acute Pain; Analgesia; Anesthesia, Conduction; Brachial Plexus; Compartment Syndromes; Emergency Medical Services; Fractures, Bone; Humans; Lower Extremity; Nerve Block; Pain Management; Pain, Postoperative; Patient Positioning; Peripheral Nerve Injuries; Peripheral Nerves; Ultrasonography, Interventional; Upper Extremity
PubMed: 30735016
DOI: 10.23736/S0375-9393.19.13145-8 -
Hand (New York, N.Y.) Jan 2023
Topics: Humans; Peripheral Nerves; Peripheral Nerve Injuries
PubMed: 36698251
DOI: 10.1177/15589447221150669