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Science Translational Medicine Aug 2023Oncomodulin (Ocm) is a myeloid cell-derived growth factor that enables axon regeneration in mice and rats after optic nerve injury or peripheral nerve injury, yet the...
Oncomodulin (Ocm) is a myeloid cell-derived growth factor that enables axon regeneration in mice and rats after optic nerve injury or peripheral nerve injury, yet the mechanisms underlying its activity are unknown. Using proximity biotinylation, coimmunoprecipitation, surface plasmon resonance, and ectopic expression, we have identified armadillo-repeat protein C10 (ArmC10) as a high-affinity receptor for Ocm. ArmC10 deletion suppressed inflammation-induced axon regeneration in the injured optic nerves of mice. ArmC10 deletion also suppressed the ability of lesioned sensory neurons to regenerate peripheral axons rapidly after a second injury and to regenerate their central axons after spinal cord injury in mice (the conditioning lesion effect). Conversely, Ocm acted through ArmC10 to accelerate optic nerve and peripheral nerve regeneration and to enable spinal cord axon regeneration in these mouse nerve injury models. We showed that ArmC10 is highly expressed in human-induced pluripotent stem cell-derived sensory neurons and that exposure to Ocm altered gene expression and enhanced neurite outgrowth. ArmC10 was also expressed in human monocytes, and Ocm increased the expression of immune modulatory genes in these cells. These findings suggest that Ocm acting through its receptor ArmC10 may be a useful therapeutic target for nerve repair and immune modulation.
Topics: Animals; Humans; Mice; Axons; Ganglia, Spinal; Induced Pluripotent Stem Cells; Nerve Regeneration; Neuronal Outgrowth; Sensory Receptor Cells
PubMed: 37556559
DOI: 10.1126/scitranslmed.adg6241 -
The Journal of Surgical Research Aug 2023Peripheral nerve injuries have been associated with increased healthcare costs and decreased patients' quality of life. Aging represents one factor that slows the speed... (Review)
Review
INTRODUCTION
Peripheral nerve injuries have been associated with increased healthcare costs and decreased patients' quality of life. Aging represents one factor that slows the speed of peripheral nervous system (PNS) regeneration. Since cellular homeostasis imbalance associated with aging lead to an increased failure in nerve regeneration in mammals of advanced age, this systematic review aims to determine the main molecular and cellular mechanisms involved in peripheral nerve regeneration in aged murine models after a peripheral nerve injuries.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature search of 4 databases was conducted in July 2022 for studies comparing the peripheral nerve regeneration capability between young and aged murine models.
RESULTS
After the initial search yielded 744 publications, ten articles fulfilled the inclusion criteria. These studies show that age-related changes such as chronic inflammatory state, delayed macrophages' response to injury, dysfunctional Schwann Cells (SCs), and microenvironment alterations cause a reduction in the regenerative capability of the PNS in murine models. Furthermore, identifying altered gene expression patterns of SC after nerve damage can contribute to the understanding of physiological modifications produced by aging.
CONCLUSIONS
The interaction between macrophages and SC plays a crucial role in the nerve regeneration of aged models. Therefore, studies aimed at developing new and promising therapies for nerve regeneration should focus on these cellular groups to enhance the regenerative capabilities of the PNS in elderly populations.
Topics: Humans; Animals; Mice; Aged; Peripheral Nerve Injuries; Quality of Life; Peripheral Nerves; Aging; Nerve Regeneration; Mammals
PubMed: 37060859
DOI: 10.1016/j.jss.2023.03.017 -
Journal of Neural Engineering Feb 2024Peripheral nerve interfaces (PNIs) are electrical systems designed to integrate with peripheral nerves in patients, such as following central nervous system (CNS)... (Review)
Review
Peripheral nerve interfaces (PNIs) are electrical systems designed to integrate with peripheral nerves in patients, such as following central nervous system (CNS) injuries to augment or replace CNS control and restore function. We review the literature for clinical trials and studies containing clinical outcome measures to explore the utility of human applications of PNIs. We discuss the various types of electrodes currently used for PNI systems and their functionalities and limitations. We discuss important design characteristics of PNI systems, including biocompatibility, resolution and specificity, efficacy, and longevity, to highlight their importance in the current and future development of PNIs. The clinical outcomes of PNI systems are also discussed. Finally, we review relevant PNI clinical trials that were conducted, up to the present date, to restore the sensory and motor function of upper or lower limbs in amputees, spinal cord injury patients, or intact individuals and describe their significant findings. This review highlights the current progress in the field of PNIs and serves as a foundation for future development and application of PNI systems.
Topics: Humans; Peripheral Nerves; Amputation, Surgical; Electrodes; Amputees; Paralysis
PubMed: 38237175
DOI: 10.1088/1741-2552/ad200f -
Biomedicine & Pharmacotherapy =... Jan 2024Bioactive macromolecular drugs known as Growth Factors (GFs), approved by the Food and Drug Administration (FDA), have found successful application in clinical practice.... (Review)
Review
Bioactive macromolecular drugs known as Growth Factors (GFs), approved by the Food and Drug Administration (FDA), have found successful application in clinical practice. They hold significant promise for addressing peripheral nerve injuries (PNIs). Peripheral nerve guidance conduits (NGCs) loaded with GFs, in the context of tissue engineering, can ensure sustained and efficient release of these bioactive compounds. This, in turn, maintains a stable, long-term, and effective GF concentration essential for treating damaged peripheral nerves. Peripheral nerve regeneration is a complex process that entails the secretion of various GFs. Following PNI, GFs play a pivotal role in promoting nerve cell growth and survival, axon and myelin sheath regeneration, cell differentiation, and angiogenesis. They also regulate the regenerative microenvironment, stimulate plasticity changes post-nerve injury, and, consequently, expedite nerve structure and function repair. Both exogenous and endogenous GFs, including NGF, BDNF, NT-3, GDNF, IGF-1, bFGF, and VEGF, have been successfully loaded onto NGCs using techniques like physical adsorption, blend doping, chemical covalent binding, and engineered transfection. These approaches have effectively promoted the repair of peripheral nerves. Numerous studies have demonstrated similar tissue functional therapeutic outcomes compared to autologous nerve transplantation. This evidence underscores the substantial clinical application potential of GFs in the domain of peripheral nerve repair. In this article, we provide an overview of GFs in the context of peripheral nerve regeneration and drug delivery systems utilizing NGCs. Looking ahead, commercial materials for peripheral nerve repair hold the potential to facilitate the effective regeneration of damaged peripheral nerves and maintain the functionality of distant target organs through the sustained release of GFs.
Topics: Humans; Peripheral Nerve Injuries; Pharmaceutical Preparations; Peripheral Nerves; Drug Delivery Systems; Macromolecular Substances; Nerve Regeneration; Sciatic Nerve
PubMed: 38113623
DOI: 10.1016/j.biopha.2023.116024 -
Arquivos de Neuro-psiquiatria Aug 2023Peripheral nerve block (PNB) is usually performed in patients with migraine who are resistant to treatment with medications.
BACKGROUND
Peripheral nerve block (PNB) is usually performed in patients with migraine who are resistant to treatment with medications.
OBJECTIVE
To compare the efficacy of PNB alone and PNB combined with prophylactic medications in migraine patients.
METHOD
The data on migraine patients who underwent PNB in our clinic between November 2019 and January 2022 were retrospectively reviewed. Blocks of the greater occipital nerve (GON), lesser occipital nerve (LON) and supraorbital nerve (SON) were performed upon admission and in the second week.
RESULTS
The study included 116 patients. While 21 out of 39 episodic migraine (EM) patients continued to use prophylactic medications, 18 were followed up with PNB alone. While 49 out of 77 chronic migraine (CM) patients continued to use prophylactic medications, 28 were followed up with PNB alone. Comparison of the admission and second-month data of the patients who only underwent PNB and those who continued the drug treatment together with PNB in both the EM and the CM group showed that the number of days with pain, number of analgesics taken and scores on the Visual Analog Scale (VAS) and the Migraine Disability Assessment (MIDAS) were significantly reduced in both groups ( < 0.01). Comparison of the second-month data of the patients followed up with PNB alone and those followed up with PNB together with prophylactic medications showed that there was no significant difference between the EM and CM patients ( > 0.05).
CONCLUSION
Bilateral GON, LON and SON block with lidocaine injection seems to be an effective treatment on its own, without the need for prophylactic medications, in both EM and CM patients during a two-month follow-up.
Topics: Humans; Anesthetics, Local; Retrospective Studies; Lidocaine; Migraine Disorders; Peripheral Nerves; Treatment Outcome
PubMed: 37536366
DOI: 10.1055/s-0043-1771494 -
Ultraschall in Der Medizin (Stuttgart,... Oct 2023The sciatic nerve (SN) is the biggest nerve in the human body and innervates a large skin surface of the lower limb and several muscles of the thigh, leg, and foot. It...
The sciatic nerve (SN) is the biggest nerve in the human body and innervates a large skin surface of the lower limb and several muscles of the thigh, leg, and foot. It originates from the ventral rami of spinal nerves L4 through S3 and contains fibers from both the posterior and anterior divisions of the lumbosacral plexus. After leaving the neural foramina, the nerve roots merge with each other forming a single peripheral nerve that travels within the pelvis and thigh. Non-discogenic pathologies of the SN are largely underdiagnosed entities due to nonspecific clinical tests and poorly described imaging findings. Likewise, to the best of our knowledge, a step-by-step ultrasound protocol to assess the SN is lacking in the pertinent literature. In this sense, the aim of the present manuscript is to describe the normal sono-anatomy of the SN from the greater sciatic foramen to the proximal thigh proposing a standardized and simple sonographic protocol. Then, based on the clinical experience of the authors, a few tips and tricks have been reported to avoid misinterpretation of confounding sonographic findings. Last but not least, we report some common pathological conditions encountered in daily practice with the main purpose of making physicians more confident regarding the sonographic "navigation" of a complex anatomical site and optimizing the diagnosis and management of non-discogenic neuropathies of the SN.
Topics: Humans; Sciatic Nerve; Peripheral Nervous System Diseases; Ultrasonography
PubMed: 37832532
DOI: 10.1055/a-2095-2842 -
Cellular and Molecular Neurobiology Oct 2023PPARγ coactivator-1 alpha (PGC-1α) is an essential transcription factor co-activator that regulates gene transcription and neural regeneration. Schwann cells, which...
PPARγ coactivator-1 alpha (PGC-1α) is an essential transcription factor co-activator that regulates gene transcription and neural regeneration. Schwann cells, which are unique glial cells in peripheral nerves that dedifferentiate after peripheral nerve injury (PNI) and are released from degenerative nerves. Wallerian degeneration is a series of stereotypical events that occurs in response to nerve fibers after PNI. The role of PGC-1α in Schwann cell dedifferentiation and Wallerian degeneration is not yet clear. As Wallerian degeneration plays a crucial role in PNI, we conducted a study to determine whether PGC-1α has an effect on peripheral nerve degeneration after injury. We examined the expression of PGC-1α after sciatic nerve crush or transection using Western blotting and found that PGC-1α expression increased after PNI. Then we utilized ex vivo and in vitro models to investigate the effects of PGC-1α inhibition and activation on Schwann cell dedifferentiation and nerve degeneration. Our findings indicate that PGC-1α negatively regulates Schwann cell dedifferentiation and nerve degeneration. Through the use of RNA-seq, siRNA/plasmid transfection and reversal experiments, we identified that PGC-1α targets inhibit the expression of paraoxonase 1 (PON1) during Schwann cell dedifferentiation in degenerated nerves. In summary, PGC-1α plays a crucial role in preventing Schwann cell dedifferentiation and its activation can reduce peripheral nerve degeneration by targeting PON1. PGC-1α inhibits Schwann cell dedifferentiation and peripheral nerve degeneration. PGC-1α negatively regulates Schwann cell dedifferentiation and peripheral nerve degeneration after injury by targeting PON1.
Topics: Humans; Aryldialkylphosphatase; Cell Dedifferentiation; Wallerian Degeneration; Schwann Cells; Sciatic Nerve; Peripheral Nerve Injuries; Nerve Regeneration
PubMed: 37526811
DOI: 10.1007/s10571-023-01395-9 -
Clinical Neurophysiology : Official... Jul 2024One hundred years ago, Erlanger and Gasser demonstrated that conduction velocity is correlated with the diameter of a peripheral nerve axon. Later, they also... (Review)
Review
One hundred years ago, Erlanger and Gasser demonstrated that conduction velocity is correlated with the diameter of a peripheral nerve axon. Later, they also demonstrated that the functional role of the axon is related to its diameter: touch is signalled by large-diameter axons, whereas pain and temperature are signalled by small-diameter axons. Certain discoveries in recent decades prompt a modification of this canonical classification. Here, we review the evidence for unmyelinated (C) fibres signalling touch at a slow conduction velocity and likely contributing to affective aspects of tactile information. We also review the evidence for large-diameter Aβ afferents signalling pain at ultrafast conduction velocity and likely contributing to the rapid nociceptive withdrawal reflex. These discoveries imply that conduction velocity is not as clear-cut an indication of the functional role of the axon as previously thought. We finally suggest that a future taxonomy of the peripheral afferent nervous system might be based on the combination of the axońs molecular expression and electrophysiological response properties.
Topics: Humans; Animals; Peripheral Nerves; Neural Conduction; Touch; Pain; Nerve Fibers, Unmyelinated; Axons
PubMed: 38704307
DOI: 10.1016/j.clinph.2024.04.008 -
Instructional Course Lectures 2024The block of sensory nerves in the ipsilateral limb or locally is an integral part of the multimodal pain management protocol after primary total knee arthroplasty. The...
The block of sensory nerves in the ipsilateral limb or locally is an integral part of the multimodal pain management protocol after primary total knee arthroplasty. The 2022 clinical practice guidelines published by the American Association of Hip and Knee Surgeons, the American Society of Regional Anesthesia and Pain Medicine, and the American Academy of Orthopaedic Surgeons describe various strengths of recommendations concerning the use of nerve blocks and periarticular injection. There is also experimental and clinical evidence to support a technique for the surgeon to perform both the periarticular injection and an intra-articular saphenous nerve block. High-dose bupivacaine injection has been shown to be effective and safe. The value of adductor canal block is currently uncertain. Future studies are needed concerning longer-lasting local anesthetic agents and techniques.
Topics: Humans; Pain, Postoperative; Bupivacaine; Anesthetics, Local; Anesthesia, Conduction; Peripheral Nerves
PubMed: 38090892
DOI: No ID Found -
Cellular and Molecular Neurobiology Nov 2023The spontaneous regeneration capacity of peripheral nerves is fundamentally reduced with advancing age, leading to severe and long-term functional loss. The cellular and...
The spontaneous regeneration capacity of peripheral nerves is fundamentally reduced with advancing age, leading to severe and long-term functional loss. The cellular and molecular basis underlying incomplete and delayed recovery of aging peripheral nerves is still murky. Here, we collected sciatic nerves of aged rats at 1d, 4d, and 7d after nerve injury, systematically analyzed the transcriptional changes of injured sciatic nerves, and examined the differences of injury responses between aged rats and young rats. RNA sequencing revealed that sciatic nerves of aged and young rats exhibit distinctive expression patterns after nerve injury. Acute and vigorous immune responses, including motivated B cell receptor signaling pathway, occurred in injured sciatic nerves of both aged and young rats. Different from young rats, aged rats have more CD8 T cells and B cells in normal state and the elevation of M2 macrophages seemed to be more robust in sciatic nerves, especially at later time points after nerve injury. Young rats, on the other hand, showed strong and early up-regulation of cell cycle-related genes. These identified unique transcriptional signatures of aged and young rats help the understanding of aged-associated injury responses in the wound microenvironments and provide essential basis for the treatment of regeneration deficits in aged population.
Topics: Rats; Animals; Peripheral Nerve Injuries; CD8-Positive T-Lymphocytes; Sciatic Nerve; Macrophages; Nerve Regeneration
PubMed: 37922116
DOI: 10.1007/s10571-023-01431-8