Nerve Research Articles

The impact of eccentric muscle contractions on peripheral nerve integrity.

Besides muscle damage, eccentric contractions also impose significant mechanical loads on peripheral nerves. However, the impact of eccentric contractions on peripheral nerve properties remains unclear. We aimed to reveal the immediate (i.e., <2 h and short-term (i.e., <10 days) effects of eccentric contractions on functional, structural, morphological, physiological and biomechanical properties of peripheral nerves. Four electronic databases (PubMed, Science Direct, PEDro and Cochrane) were searched for animal and human studies which evaluated the immediate and/or short-term impact of eccentric contractions of upper or lower limb muscles on outcomes related functional, structural, morphological, physiological and biomechanical properties of peripheral nerves. From a total of 2415 articles, two human and two animal studies met the selection criteria. Several signs of nerve damage following eccentric exercises were observed, such as reductions in myelin sheath thickness, nerve fibre diameter, sensory and motor nerve conduction velocity, and protein zero levels, alongside increased levels of macrophage-related protein and tropomyosin receptor kinase C. No significant changes were identified in growth-associated protein 43. It is worth noting that some variables exhibited differences in their time course between human and animal studies. Animal studies revealed that the effects were more pronounced when eccentric contractions were performed at higher velocities. Current evidence is suggestive that eccentric contractions has the potential to alter the peripheral nerves structural, morphological, functional and physiological properties, which are indicative of nerve damage. CRD42021285767.

GFRα1 Promotes Axon Regeneration after Peripheral Nerve Injury by Functioning as a Ligand.

The neurotrophic factor, Glial cell line derived neurotrophi factor (GDNF), exerts a variety of biological effects through binding to its receptors, GDNF family receptor alpha-1 (GFRα1), and RET. However, the existence of cells expressing GFRα1 but not RET raises the possibility that GFRα1 can function independently from RET. Here, it is shown that GFRα1 released from repair Schwann cells (RSCs) functions as a ligand in a GDNF-RET-independent manner to promote axon regeneration after peripheral nerve injury (PNI). Local administration of GFRα1 into injured nerve promoted axon regeneration, even more when combined with GDNF blockade. GFRα1 bound to a receptor complex consisting of NCAM and integrin α7β1 of dorsal root ganglion neurons in a GDNF-RET independent manner. This is further confirmed by the Ret Y1062F knock-in mice, which cannot transmit most of GDNF-RET signaling. Finally, local administration of GFRα1 into injured sciatic nerve promoted functional recovery. These findings reveal a novel role of GFRα1 as a ligand, the molecular mechanism supporting axon regeneration by RSCs, and a novel therapy for peripheral nerve repair.

Biomimetic Versatile Anisotropic, Electroactive Cellulose Hydrogel Scaffolds Tailored from Fern Stem Serving as Nerve Conduit and Cardiac Patch.

Peripheral nerve injury (PNI) and myocardial infarction (MI) are the two most clinically common soft excitable tissue injuries. Both nerve and cardiac tissues exhibit structural anisotropy and electrophysiological activity, providing a wide range of biophysical cues for cell and tissue repair. However, balancing microstructural anisotropy, electroactivity, and biocompatibility is challenging. To address this issue, Dicranopteris linearis (D. linearis) is proposed as a low-perceived value fern plant. Moreover, to enhance its usefulness, it can be designed into a tubular structure and a lamellar structure to bridge the damaged tissue. Therefore, a robust yet simple top-down approach is proposed to designing and fabricating the desired biomimetic versatile hydrogels orienting from the D. linearis to customize for different soft excitable tissue repair applications. These anisotropic electroactive hydrogels performed well as nerve guidance conduits (NGC) and engineered cardiac patches (ECP) in the repair of PNI and MI, respectively. Two birds, one stone. Accordingly, the biomimetic strategy of D. linearis to NGC and D. linearis to ECP is first proposed, opening a new horizon for constructing tissue engineering using natural sources.

Retrospective Analysis of Functional and Demographic Data of Earthquake-Related Peripheral Nerve Injuries

Retrospective Analysis of Functional and Demographic Data of Earthquake-Related Peripheral Nerve Injuries

Anatomical study of the innervation of the posterior elbow joint capsule: implications for ultrasound-guided peripheral nerve block and radiofrequency ablation procedures

IntroductionUltrasound-guided peripheral nerve block and radiofrequency ablation have been developed for pain management in various joints including the hip, knee and shoulder, but not the elbow. Precise three-dimensional (3D) localization...

Mechanism and Application of Chinese Herb Medicine in Treatment of Peripheral Nerve Injury.

Peripheral nerve injury (PNI) encompasses damage to nerves located outside the central nervous system, adversely affecting both motor and sensory functions. Although peripheral nerves possess an intrinsic capacity for self-repair, severe injuries frequently result in significant tissue loss and erroneous axonal junctions, thereby impeding complete recovery and potentially causing neuropathic pain. Various therapeutic strategies, including surgical interventions, biomaterials, and pharmacological agents, have been developed to enhance nerve repair processes. While preclinical studies in animal models have demonstrated the efficacy of certain pharmacological agents in promoting nerve regeneration and mitigating inflammation, only a limited number of these agents have been translated into clinical practice to expedite nerve regeneration. Chinese herb medicine (CHM) possesses a longstanding history in the treatment of various ailments and demonstrates potential efficacy in addressing PNI through its distinctive, cost-effective, and multifaceted methodologies. This review critically examines the advancements in the application of CHM for PNI treatment and nerve regeneration. In particular, we have summarized the most commonly employed and rigorously investigated CHM prescriptions, individual herbs, and natural products, elucidating their respective functions and underlying mechanisms in the context of PNI treatment. Furthermore, we have deliberated on the prospective development of CHM in both clinical practice and fundamental research.

Cellular and molecular characterization of peripheral glia in the lung and other organs.

Peripheral glia are important regulators of diverse physiologic functions yet their molecular distinctions and locations in almost all visceral organs are not well-understood. We performed a systematic analysis of peripheral glia, focusing on the lung and leveraging single cell RNA sequencing (scRNA-seq) analysis to characterize their cellular and molecular features. Using in vivo lineage studies, we characterized the anatomic, cellular, and molecular features of the Sox10+ glial lineage of the mouse lung. Using high-resolution imaging, we quantified the distribution and cellular morphologies of myelinating, non-myelinating, satellite, and terminal glial cells with their intricate extensions along peripheral nerves, including terminals at specialized neurosensory structures within the lung. Spatial analysis of selectively expressed myelinating (periaxin/Prx, claudin 19/Cldn) or non-myelinating (sodium channel/Scn7a) glial cell genes identified by scRNA-seq analysis revealed molecularly distinct populations surrounding myelinated nerve fibers in the lung. To extend this analysis to primates and other organs, we extracted rare peripheral glial cells in whole organism scRNA-seq atlases of mouse lemur and human. Our cross-species data analysis and integration of scRNA-seq data of ~700 peripheral glial cells from mouse, mouse lemur, and human glial cells identified conserved gene expression of molecularly distinct peripheral glial cell populations. This foundational knowledge facilitates subsequent functional studies targeting molecularly distinct subsets of peripheral glia and integrating them into organ-specific disorders of autonomic dysregulation. In addition, our cross-species analysis identifying conserved gene expression patterns and glial networks in extrapulmonary organs provides a valuable resource for studying the functional role of peripheral glia in multiorgan human diseases.

Synthetic conduits efficacy in neural repair: a comparative study of dip-coated polycaprolactone and electrospun polycaprolactone/ polyurethane conduits.

Peripheral nerve injuries represent the most common type of nervous system injuries, resulting in 5 million injuries per year. Current gold standard, autografts, still carry several limitations, including the inappropriate type, size, and function matches in grafted nerves, lack of autologous donor sites, neuroma formation, and secondary surgery incisions. Polymeric nerve conduits, also known as nerve guides, can help overcome the aforementioned issues that limit nerve recovery and regeneration by reducing tissue fibrosis, misdirection of regenerating axons, and the inability to maintain long- distance axonal growth. Polymer-based double-walled microspheres (DWMS) are designed to locally and in a sustainable fashion deliver bioactive agents. Lysozyme is a natural antimicrobial protein that shares similar physical and chemical properties to glial cell line-derived neurotrophic factor (GDNF), making it an ideal surrogate molecule to evaluate the release kinetics of encapsulated bioagent from polymeric biodegradable microspheres embedded in Polycaprolactone and Polycaprolactone/Polyurethane blend nerve conduits.&#xD;Approach: Lysozyme was encapsulated in poly(lactic-co-glycolic acid)/poly(L-lactide) (PLGA/PLLA) double-walled microspheres fabricated through a modified water-oil-water emulsion solvent evaporation method. Lysozyme-loaded DWMS were further embedded in PCL and PCL-PU based nerve guides constructed via polymer dip-coating and electrospinning method respectively. Lysozyme DWMS and nerve guides were imaged using scanning electron microscopy (SEM). Released lysozyme concentration was determined by using a colorimetric micro-BCA protein assay and spectrophotometric quantitation. Tensile and suture pull-out tests were utilized to evaluate the mechanical properties of both dip-coated and electrospun nerve guides, embedded and free of lysozyme DWMS.&#xD;Main Results: The study revealed significant distinctions in the lysozyme release profiles, and mechanical properties of the manufactured polymer nerve guides. Both PCL dip-coated and PCL/PU electrospun DWMS-embedded nerve guides revealed biphasic protein release profiles. PCL/PU electrospun and PCL dip-coated nerve guides released 16% and 29% of the total protein concentration within 72 hours, plateauing at week 16 and week 8, respectively. SEM analysis of the nerve guides confirmed the homogeneity and integrity of the polymer nerve guides' structures. The electrospun guides were found to be more flexible with a higher extension under stress bending, while the dip-coated PCL nerve guides displayed more rigid behavior.&#xD;Significance: This study provides useful insights on how to optimize nerve guide design and fabrication to enhance recovery progress of peripheral nerve injuries.&#xD.

PKN2 Promotes Peripheral Nerve Repair by Regulating Autophagy via Activation of the AKT-mTOR Pathway: An In Vitro Study.

This study aims to explore the role of Protein Kinase N2 (PKN2) in peripheral nerve injury (PNI) and evaluate its potential as a therapeutic target. The study employed a PC12 cell model to assess the effects of PKN2 overexpression on cell proliferation, migration, synaptic growth, and autophagic activity, with a focus on the regulatory role of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. The results demonstrated that PKN2 overexpression significantly promoted PC12 cell proliferation and cell migration, while also enhancing synaptic growth. Additionally, a significant suppression of autophagy was observed. Mechanistic analysis revealed that PKN2 inhibited autophagic activity through the activation of the AKT/mTOR pathway. In summary, PKN2 plays a significant role in peripheral nerve repair by promoting cell proliferation, migration, and synaptic growth, while inhibiting autophagy through the AKT/mTOR pathway. These findings suggest that targeting PKN2 may represent an effective therapeutic strategy for the treatment of PNI.

Recent Advancements in Bioelectronic Medicine: A Review.

Bioelectronic medicine is a multidisciplinary field that combines molecular medicine, neurology, engineering, and computer science to design devices for diagnosing and treating diseases. The advancements in bioelectronic medicine can improve the precision and personalization of illness treatment. Bioelectronic medicine can produce, suppress, and measure electrical activity in excitable tissue. Bioelectronic devices modify specific neural circuits using electrons rather than pharmaceuticals and uses of bioelectronic processes to regulate the biological processes underlining various diseases. This promotes the potential to address the underlying causes of illnesses, reduce adverse effects, and lower costs compared to conventional medication. The current review presents different important aspects of bioelectronic medicines with recent advancements. The area of bioelectronic medicine has a lot of potential for treating diseases, enabling non-invasive therapeutic intervention by regulating brain impulses. Bioelectronic medicine uses electricity to control biological processes, treat illnesses, or regain lost capability. These new classes of medicines are designed by the technological developments in the detection and regulation of electrical signaling methods in the nervous system. Peripheral nervous system regulates a wide range of processes in chronic diseases; it involves implanting small devices onto specific peripheral nerves, which read and regulate the brain signaling patterns to achieve therapeutic effects specific to the signal capacity of a particular organ. The potential for bioelectronic medicine field is vast, as it investigates for treatment of various diseases, including rheumatoid arthritis, diabetes, hypertension, paralysis, chronic illnesses, blindness, etc.

A new approach to peripheral nerve block education with the Anatomage Table as a learning adjunct.

Human anatomy education serves as a gateway for entering the intricacies of health science. Human cadavers have been the gold standard for learning regional and gross anatomy. However, increasing barriers in acquisition, maintenance, and longevity have pushed anatomy education toward technology-based alternatives such as the Anatomage Table (AT), an interactive, life-sized virtual dissection table with many anatomy education-centric features. The AT has found purchase in various contexts, such as clinical settings, research, outreach, and education. Studies into the efficacy of the AT in teaching settings have been generally positive but limited in its application, particularly in clinical procedure education. In this study, we conducted an informal workshop for second-year Certified Registered Nurse Anesthetist (CRNA) students to aid in being able to identify the important neuraxial landmarks for performing peripheral nerve blocks (PNBs), an anesthetic technique often used before other procedures. In our workshop, we paired the AT with identification of the same neuraxial landmarks on volunteer models with an ultrasound probe to provide students with relevant tactile experience for the procedure. From our pre-/post-surveys of the participants (n = 29), we found that our workshop significantly increased student confidence in identifying the relevant neuraxial landmarks for and in performing PNBs. Our results support the use of the AT in clinical education as a supplement, particularly where other anatomic teaching tools, such as cadaver models, may be too difficult to implement.NEW & NOTEWORTHY We implemented the Anatomage Table (AT) and portable ultrasound to teach neuraxial landmarks for performing peripheral nerve blocks (PNB), an anesthetic technique for Certified Registered Nurse Anesthetist (CRNA) students. The workshop significantly increased student confidence in identifying the relevant neuraxial landmarks for performing PNBs. Our results support the use of the AT in clinical education as a supplement.

Enhancing ultrasound-guided brachial plexus nerve localization with ResNet50 and support vector machine

&lt;p&gt;Medical image segmentation and classification plays a vital role in nerve block/region identification, particularly for anesthesiologists relying on instinctual judgments. However, due to patient-specific anatomical variations, these methods sometimes lack precision. This research focuses on addressing the problem, by incorporating novel ensembling method of ResNet-50 and support vector machine (SVM) to achieve segmentation of dataset images and classification of nerve blocks respectively. The said novel ensemble model is trained on a publicly available dataset consisting of more than 16,800 images. The sole purpose of this work is to address the problem of peripheral nerve blocking (PNB) with the usage of ensemble modelling, while achieving the highest possible accuracy. This research will help practitioners in accurately identifying the location of brachial plexus and distinguishing the type of nerve block to be injected – interscalene and supraclavicular. The model, which integrates ResNet50 and SVM classifier, achieved a commendable 99.27% accuracy in identifying and classifying the brachial plexus region.&lt;/p&gt;

The analgesic effect of acupuncture in neuropathic pain: regulatory mechanisms of DNA methylation in the brain

Abstract Recent research has demonstrated that chronic pain, resulting from peripheral nerve injury, leads to various symptoms, including not only allodynia and hyperalgesia but also anxiety, depression, and cognitive impairment. These symptoms are believed to arise due to alterations in gene expression and neural function, mediated by epigenetic changes in chromatin structure. Emerging evidence suggests that acupuncture can modulate DNA methylation within the central nervous system, contributing to pain relief and the mitigation of comorbidities. Specifically, acupuncture has been shown to adjust the DNA methylation of genes related to mitochondrial dysfunction, oxidative phosphorylation, and inflammation pathways within cortical regions, such as the prefrontal cortex, anterior cingulate cortex, and primary somatosensory cortex. In addition, it influences the DNA methylation of genes associated with neurogenesis in hippocampal neurons. This evidence indicates that acupuncture, a treatment with fewer side effects compared with conventional medications, could offer an effective strategy for pain management.

Validation of Peripheral Neuromodulation Mechanisms of Icariin in Knee Osteoarthritis–Related Chronic Pain

ABSTRACTKnee osteoarthritis (KOA) is a chronic degenerative joint disease‐causing chronic pain and disability. Neuromodulation of subchondral bone affects KOA‐related pain and involves dorsal root ganglion (DRG). Our previous studies have demonstrated efficacy of icariin (ICA) in treating KOA, but neuromodulation mechanisms in peripheral nerves associated with the treatment of chronic pain in KOA remain unclear. This study aimed to investigate peripheral neuromodulation mechanisms of ICA in KOA‐related chronic pain: (1) assessing therapeutic effect of ICA in a rat model of KOA‐induced chronic pain; (2) investigating changes in pain‐related nerve fibres and transient receptor potential vanilloid Subfamily 1 (TRPV1) pathway in subchondral bone following ICA treatment; and (3) exploring expression of pain‐related Nogo‐A/TRPV1 pathway in DRG, thereby elucidating neurotransmission of pain. Experimental results confirmed the curative effect of ICA on KOA by relieving chronic pain and pathological changes. ICA also effectively reduced bone remodelling, the area of pain‐related positive nerve fibres and expression of TRPV1 in subchondral bone. Furthermore, ICA downregulated pain‐related Nogo‐A/TRPV1 pathway in the DRG. These findings provide new mechanistic insights into the therapeutic potential of ICA in relieving peripheral nervous system‐related chronic pain in KOA.

Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression.

Although the role of peripheral nerves in cancer progression has been appreciated, little is known regarding cancer/sensory nerve crosstalk and its contribution to bone metastasis and associated pain. In this study, we revealed that the cancer/sensory nerve crosstalk plays a crucial role in bone metastatic progression. We found that (i) periosteal sensory nerves expressing calcitonin gene-related peptide (CGRP) are enriched in mice with bone metastasis; (ii) cancer patients with bone metastasis have elevated CGRP serum levels; (iii) bone metastatic patient tumor samples express elevated calcitonin receptor-like receptor (CRLR, a CGRP receptor component); (iv) higher CRLR levels in cancer patients are negatively correlated with recurrence-free survival; (v) CGRP induces cancer cell proliferation through the CRLR/p38/HSP27 pathway; and (vi) blocking sensory neuron-derived CGRP reduces cancer cell proliferation in vitro and bone metastatic progression in vivo. This suggests that CGRP-expressing sensory nerves are involved in bone metastatic progression and that the CGRP/CRLR axis may serve as a potential therapeutic target for bone metastasis.

Current Concepts in the Molecular Mechanisms and Management of Diabetic Neuropathy by Pharmacotherapeutics and Natural Compounds.

One of the most crippling effects of diabetes mellitus is diabetic neuropathy, which can cause discomfort, loss of movement, and even amputation. Diabetic neuropathy manifests in a variety of ways, ranging from pain to death. Diagnosing diabetic neuropathy can be challenging since it often goes unnoticed for many years following the onset of diabetes. In addition to oxidative stress in neurons, hyperglycemia activates a number of metabolic pathways that are important sources of damage and possible targets for treatment in diabetic neuropathy. Downstream metabolic cascades caused by prolonged hyperglycemia include activation of protein kinase C, increased production of advanced glycation end products, excessive release of cytokines, increased oxidative stress, and injury to peripheral nerves. Despite the fact that these metabolic anomalies are considered the main cause of diabetes-related microvascular issues, the diverse mechanistic processes of neuropathy are characterized by organ-specific histological and biochemical features. Although the symptoms of diabetic neuropathy can be treated, there are few options to correct the underlying problem. Diabetic neuropathy exerts a tremendous financial, psychological, and physical burden on society, emphasizing the need for efficient and focused treatment. The major goal of this review is to shed light on the multiple mechanisms and pathways that contribute to the onset of diabetic neuropathy and to provide readers with a comprehensive understanding of emerging therapeutic strategies to postpone or reverse various forms of diabetic neuropathy. The article discusses available medications and provides the latest guidelines for the treatment of pain and distal symmetric polyneuropathy, including diabetic autonomic neuropathy, which may help the patients control pain well and assess alternatives for treatment that might be more successful in preventing or delaying the course of a disease.

Evaluation of needle to nerve interaction for neurological complications in ultrasound-guided interscalene brachial plexus blocks

BackgroundThe use of regional anesthesia techniques carries a well-known risk of perioperative neurological complications. The interscalene approach to brachial plexus block (ISB) is associated with the largest risk of neurological complications of any peripheral nerve block. The reported incidence of nerve injury after ISB varies, with estimates ranging from 0.5 % to 3 % of cases. In this prospective study, we sought to correlate the needle-to-nerve interaction during ISB procedures with the development of post-operative neurological outcomes. MethodsA novel grading system was developed to categorize various needle tip positions during ISB procedures. De-identified ultrasound recordings were graded post-procedure by two independent radiologists. These video grades were correlated with the incidence of post-procedural numbness or paresthesia and post-operative pain scores in the PACU and 24 hours postoperatively. Results108 patient videos were included for analysis. Zero videos received grade 1 (intraneural injection), 20 % received grade 2 (injection with needle against nerve root), 68 % received grade 3 (injection inside brachial plexus sheath), and 12 % received grade 4 (injection external to sheath). There was no statistical difference in terms of post-operative neurological complications or pain scores across the grades. Only four patients experienced post-operative neurologic complications on day one, and seven patients had neurological symptoms on day two. All symptoms resolved by post-operative day five. ConclusionsOur scoring system did not reveal relationship between more aggressive needling techniques and adverse post-procedural neurological symptoms. There was also no difference in pain scores across video grades, indicating that injection within the nerve sheath did not lead to better postoperative pain scores compared to injection outside the sheath. Since no procedures were found to be intraneural by the reviewing radiologists, no relationship between intraneural needling and adverse neurological outcomes could be elucidated. Larger studies in diverse settings may be required to capture greater variation in the block grades for more statistical power.

Unusual presentation of a posterior mediastinal schwannoma associated with chest pain, cough and dyspnea

Neurogenic tumors (NT) are the most common of posterior mediastinal tumors, an 80% of all posterior mediastinal tumors are (NT). They originate from the spinal cord, sympathetic ganglia, or peripheral nerve roots. A Schwannoma is a slow-growing, encapsulated, and benign neurogenic tumor. Fewer than 9% of Schwannoma are located in the mediastinum. Posterior mediastinal Schwannoma originates from neural crest cells and typically from the intercostal nerves. Mediastinal Schwannoma is often asymptomatic but may present with unusual symptoms such as cough or dyspnea and hemoptysis because of pulmonary involvement. Although a definitive diagnosis is made by histopathology and immunohistochemically analysis, electron microscopy can be used to help item final diagnosis. We present a case of a benign posterior mediastinal Schwannoma, which is present in CXR and computed tomography (CT) imaging as a cystic lesion in a 58-year-old woman who was admitted to our hospital with back pain, cough, hemoptysis, and dyspnea.

Neurofibroma unusual site, the nasal tip: Case report

Neurofibromas are considered as benign tumors of the peripheral nerve sheath which originates from the proliferation of elements of the peripheral nerve including; Schwann cells, axons, fibroblasts, perineurial and endoneurial cells. Neurofibroma can arise in any anatomic location, however having a neurofibroma originating from the external nose more specifically the nasal tip is extremely rare. In this article we are presenting a rare case of nasal tip neurofibroma in 11 years old female child.

Evolution of natural polymer nerve conduit technology in peripheral nerve repair: a narrative review

Peripheral nerve injury is a worldwide challenge in the clinic. Although autologous nerve is considered the gold standard for bridging large nerve defects (&gt; 5 mm), donor-site morbidity, limited sources of donor nerves and other potential side effects restrict its application in nerve regeneration. Nerve guidance conduits have become increasingly popular as a promising alternative to autologous nerve repair and regeneration. The evolution of nerve guidance conduits from nondegradable materials to various biodegradable materials subsequently results in enhanced properties, such as superior biodegradability, a mimetic extracellular matrix and an optimal structure. This review describes current therapies for nerve repair and the mechanism and evolution of nerve guidance conduits with advantages and limitations; proposes the detailed requirements of ideal nerve guidance conduits; and emphasizes the applications of natural polymers, including collagen, chitosan, alginate, gelatin, silk fibroin and hyaluronic acid, in nerve regeneration with the incorporation of various functional materials, chemical modifications and feasible techniques to promote cell proliferation and axon regeneration. Compared with natural polymers, advanced nerve guidance conduits have considerable potential for nerve regeneration in the clinic.