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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 -
Hand Clinics Aug 2013Peripheral nerve injuries are common conditions, with broad-ranging groups of symptoms depending on the severity and nerves involved. Although much knowledge exists on... (Review)
Review
Peripheral nerve injuries are common conditions, with broad-ranging groups of symptoms depending on the severity and nerves involved. Although much knowledge exists on the mechanisms of injury and regeneration, reliable treatments that ensure full functional recovery are scarce. This review aims to summarize various ways these injuries are classified in light of decades of research on peripheral nerve injury and regeneration.
Topics: Animals; Axons; Cells, Cultured; Humans; Macrophages; Models, Animal; Models, Biological; Nerve Compression Syndromes; Nerve Fibers; Nerve Growth Factors; Nerve Regeneration; Neurons; Peripheral Nerve Injuries; Peripheral Nerves; Schwann Cells; Wallerian Degeneration
PubMed: 23895713
DOI: 10.1016/j.hcl.2013.04.002 -
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 -
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 -
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 -
BioMed Research International 2014Unlike other tissues in the body, peripheral nerve regeneration is slow and usually incomplete. Less than half of patients who undergo nerve repair after injury regain... (Review)
Review
Unlike other tissues in the body, peripheral nerve regeneration is slow and usually incomplete. Less than half of patients who undergo nerve repair after injury regain good to excellent motor or sensory function and current surgical techniques are similar to those described by Sunderland more than 60 years ago. Our increasing knowledge about nerve physiology and regeneration far outweighs our surgical abilities to reconstruct damaged nerves and successfully regenerate motor and sensory function. It is technically possible to reconstruct nerves at the fascicular level but not at the level of individual axons. Recent surgical options including nerve transfers demonstrate promise in improving outcomes for proximal nerve injuries and experimental molecular and bioengineering strategies are being developed to overcome biological roadblocks limiting patient recovery.
Topics: Animals; Humans; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Plastic Surgery Procedures; Recovery of Function; Translational Research, Biomedical
PubMed: 25276813
DOI: 10.1155/2014/698256 -
Hand (New York, N.Y.) Jan 2023
Topics: Humans; Peripheral Nerves; Peripheral Nerve Injuries
PubMed: 36698251
DOI: 10.1177/15589447221150669 -
Journal of Visualized Experiments : JoVE Oct 2021Peripheral nerve interfaces are frequently used in experimental neuroscience and regenerative medicine for a wide variety of applications. Such interfaces can be...
Peripheral nerve interfaces are frequently used in experimental neuroscience and regenerative medicine for a wide variety of applications. Such interfaces can be sensors, actuators, or both. Traditional methods of peripheral nerve interfacing must either tether to an external system or rely on battery power that limits the time frame for operation. With recent developments of wireless, battery-free, and fully implantable peripheral nerve interfaces, a new class of devices can offer capabilities that match or exceed those of their wired or battery-powered precursors. This paper describes methods to (i) surgically implant and (ii) wirelessly power and control this system in adult rats. The sciatic and phrenic nerve models were selected as examples to highlight the versatility of this approach. The paper shows how the peripheral nerve interface can evoke compound muscle action potentials (CMAPs), deliver a therapeutic electrical stimulation protocol, and incorporate a conduit for the repair of peripheral nerve injury. Such devices offer expanded treatment options for single-dose or repeated dose therapeutic stimulation and can be adapted to a variety of nerve locations.
Topics: Animals; Electric Power Supplies; Electric Stimulation Therapy; Peripheral Nerves; Phrenic Nerve; Prostheses and Implants; Rats; Wireless Technology
PubMed: 34747395
DOI: 10.3791/63085 -
BioMed Research International 2014
Topics: Animals; Biocompatible Materials; Humans; Nerve Regeneration; Peripheral Nerves; Stem Cell Transplantation; Translational Research, Biomedical; Wound Healing
PubMed: 25276783
DOI: 10.1155/2014/381426