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Introduction: Traumatic peripheral nerve injuries pose significant challenges to healthcare systems and individuals, affecting sensory function, causing neuropathic pain, and impairing quality of life. Despite their impact, comprehensive studies on the epidemiology and regional variance of these injuries are scarce. Understanding the incidence, trends, and anatomical distribution of such injuries is essential for targeted interventions and resource allocation., Methods: This observational study utilized register-based data from the Swedish National Patient Register covering the period from 2008 to 2022. Incidence rates, trends, and anatomical distribution of traumatic peripheral nerve injuries were analyzed using descriptive statistics, Poisson regression modeling, and regional comparisons., Results: Higher incidences of peripheral nerve injuries were observed among men compared to women across all age groups. The hand and wrist were the most commonly affected sites. Regional variations in incidence rates were evident, with some regions consistently exhibiting higher rates compared to others. Notably, a decreasing trend in injuries was observed over the study period., Conclusion: This study underscores the importance of targeted interventions and preventive strategies, considering sex, age, and regional disparities. Further research incorporating individual patient-level data is warranted to enhance our understanding and inform tailored interventions to reduce the burden of these injuries., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Magnéli, Axenhus. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Nerve lesions often heal incompletely, leading to lifelong functional impairment and high costs for the health care system. The updated German clinical practice guideline is intended to promote the early recognition of nerve lesions and the timely initiation of proper treatment for optimal restoration of function., Methods: The recommendations are based on an assessment of all the evidence revealed by a systematic search of the literature, as well as on the expertise of the multiprofessional guideline group., Results: Only a few publications contain high-quality evidence. This version of the guideline contains a more detailed discussion of war injuries, iatrogenic injuries, MR neurography, and specific treatments than the previous version. As for the different methods of nerve replacement, a comparison of autologous transplantation versus the use of conduits and tubes revealed no significant difference between these two methods on the mBMRC scale, and minimal superiority of autologous transplantation with respect to two-point discrimination. As for the use of nerve transfers when nerve reconstruction is not feasible or unlikely to succeed, nerve transfer yielded slightly better results than proximal reconstruction for elbow flexion, but the difference did not reach statistical significance (mBMRC ≥ 3: RR 1.16, 95% confidence interval [1.02; 1.32]). The treatment of neuromas with targeted muscle reinnervation was superior to the classic approach in decreasing both stump pain (MD 2.0 +/- 2.8) and phantom limb pain (MD 3.4 +/- 4.03)., Conclusion: The delayed or improper treatment of peripheral nerve lesions can lead to severe impairment. Timely diagnosis, the use of appropriate treatments in conformity with the guidelines, and interdisciplinary collaboration among specialists are all essential for optimizing the outcome.

Background: Peripheral nerve damage mainly resulted from traumatic or infectious causes; the main signs of a damaged nerve are the loss of sensory and/or motor functions. The injured nerve has limited regenerative capacity and is recovered by the body itself, the recovery process depends on the severity of damage to the nerve, nowadays the use of stem cells is one of the new and advanced methods for treatment of these problems., Method: Following our review, data are collected from different databases "Google scholar, Springer, Elsevier, Egyptian Knowledge Bank, and PubMed" using different keywords such as Peripheral nerve damage, Radial Nerve, Sciatic Nerve, Animals, Nerve regeneration, and Stem cell to investigate the different methods taken in consideration for regeneration of PNI., Result: This review contains tables illustrating all forms and types of regenerative medicine used in treatment of peripheral nerve injuries (PNI) including different types of stem cells " adipose-derived stem cells, bone marrow stem cells, Human umbilical cord stem cells, embryonic stem cells" and their effect on re-constitution and functional recovery of the damaged nerve which evaluated by physical, histological, Immuno-histochemical, biochemical evaluation, and the review illuminated the best regenerative strategies help in rapid peripheral nerve regeneration in different animal models included horse, dog, cat, sheep, monkey, pig, mice and rat., Conclusion: Old surgical attempts such as neurorrhaphy, autogenic nerve transplantation, and Schwann cell implantation have a limited power of recovery in cases of large nerve defects. Stem cell therapy including mesenchymal stromal cells has a high potential differentiation capacity to renew and form a new nerve and also restore its function., (© 2023. The Author(s).)

Traumatic peripheral nerve injury (TPNI) is quite common in various types of acral trauma. It mostly passes unnoticed at the time of the initial trauma. The patients are usually sent for an ultrasound (US) assessment about 4 weeks following the trauma, after the electrophysiological changes are established. This paper presents a 5‐year experience of US findings of TPNI through 60 cases, who were examined as an outpatient with clinical and electrodiagnostic (EDX) tests suggesting nerve injury. The study population includes 40 males, 20 females, and mean age 34.4 ± 16.3. Upper limb nerves were more affected than the lower ones, with no significant difference between the right and left sides. Mechanisms of injury include laceration in 53.4% of cases, 38.3% had history of traction injury and only 8.3% had history of compression/contusion injury. Regarding the severity grading of the injuries, long segments of thickened separate or matted fascicles (Grades I and II) was found in 27 (40.9%) nerves; partial disruption with interstitial neuroma (Grade III) in 15 (22.7%) nerves; complete disruption (neurotmesis) (Grade IV) in 24 (36.4%) case. The integrity of six repaired nerves was also assessed. Muscle states within the territory of the motor nerve were always assessed, 62.9% of cases had decreased muscle bulk, 28.6% had muscle atrophy, and the remaining was normal. EDX testing results of 44 out of 60 patients was severe in 14 cases (31.8%), moderate in 15 cases (34.1%), mild in 11 case (25%), and normal in four cases (9.1%). The purpose of this study is to demonstrate that the US is a convenient neuroimaging tool by which we can accurately determine the level and the degree of peripheral nerve damage to plan the appropriate treatment. [ABSTRACT FROM AUTHOR]

Aim: Peripheral nerve injury (PNI) is a debilitating condition with significant associated morbidity, and which places a substantial socioeconomic burden on healthcare systems worldwide. Recently, allograft has emerged as a viable surgical alternative to autograft for the treatment of PNI. This study evaluated the cost effectiveness of allograft (Avance ® Nerve Graft) compared with autograft for the peripheral nerve repair, from a US payer perspective. Methods: A Markov cohort model was developed to consider the treatment pathways followed by a patient population undergoing a single transected nerve repair with either allograft, or autograft. The marginal difference in meaningful recovery (MR) (effectiveness), and costs, between the two groups were estimated over a lifetime horizon. Deterministic and probabilistic sensitivity analyses (PSA) were performed to consider the uncertainty surrounding the base-case input parameter values and their effect on the overall incremental cost-effectiveness ratio (ICER). Results: The base-case analysis indicates that there is a small difference in the average probability of MR between the two groups (75.15% vs 70.46%; +4.69% with allograft). Allograft also results in cost savings ($12,677 vs $14,023; -$-1346 with allograft) compared with autograft. Deterministic sensitivity analysis shows that the costs of the initial surgical procedures are the main drivers of incremental cost, but that the intervention is likely to be cost saving compared with autograft regardless of the parameter variations made. Conclusion: The use of allograft with the Avance Nerve Graft has the potential to be a cost-effective alternative to autograft for the surgical treatment of PNI in the USA.

Neurological diseases are destructive, mainly characterized by the failure of endogenous repair, the inability to recover tissue damage, resulting in the increasing loss of cognitive and physical function. Although some clinical drugs can alleviate the progression of these diseases, but they lack therapeutic effect in repairing tissue injury and rebuilding neurological function. More and more studies have shown that cell therapy has made good achievements in the application of nerve injury. Olfactory ensheathing cells (OECs) are a special type of glial cells, which have been proved to play an important role as an alternative therapy for neurological diseases, opening up a new way for the treatment of neurological problems. The functional mechanisms of OECs in the treatment of neurological diseases include neuroprotection, immune regulation, axon regeneration, improvement of nerve injury microenvironment and myelin regeneration, which also include secreted bioactive factors. Therefore, it is of great significance to better understand the mechanism of OECs promoting functional improvement, and to recognize the implementation of these treatments and the effective simulation of nerve injury disorders. In this review, we discuss the function of OECs and their application value in the treatment of neurological diseases, and position OECs as a potential candidate strategy for the treatment of nervous system diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Liao, Liu, Luo and Zhang.)

Peripheral nerve injuries are common neurological disorders, and the available treatment options, such as conservative management and surgical repair, often yield limited results. However, there is growing interest in the potential of using chitosan-based biopolymers as a novel therapeutic approach to treating these injuries. Chitosan-based biopolymers possess unique characteristics, including biocompatibility, biodegradability, and the ability to stimulate cell proliferation, making them highly suitable for repairing nerve defects and promoting nerve regeneration and functional recovery. Furthermore, these biopolymers can be utilized in drug delivery systems to control the release of therapeutic agents and facilitate the growth of nerve cells. This comprehensive review focuses on the latest advancements in utilizing chitosan-based biopolymers for peripheral nerve regeneration. By harnessing the potential of chitosan-based biopolymers, we can pave the way for innovative treatment strategies that significantly improve the outcomes of peripheral nerve injury repair, offering renewed hope and better prospects for patients in need.

Background: Peripheral nerve injuries (PNIs) include several conditions in which one or more peripheral nerves are damaged. Trauma is one of the most common causes of PNIs and young people are particularly affected. They have a significant impact on patients' quality of life and on the healthcare system, while timing and type of surgical treatment are of the utmost importance to guarantee the most favorable functional recovery. To date, several different classifications of PNIs have been proposed, most of them focusing on just one or few aspects of these complex conditions, such as type of injury, anatomic situation, or prognostic factors. Current classifications do not enable us to have a complete view of this pathology, which includes diagnosis, treatment choice, and possible outcomes. This fragmentation sometimes leads to an ambiguous definition of PNIs and the impossibility of exchanging crucial information between different physicians and healthcare structures, which can create confusion in the choice of therapeutic strategies and timing of surgery., Materials: The authors retrospectively analyzed a group of 24 patients treated in their center and applied a new classification for PNI injuries. They chose (a) five injury-related factors, namely nerve involved, lesion site, nerve type (whether motor, sensory or mixed), surrounding tissues (whether soft tissues were involved or not), and lesion type-whether partial/in continuity or complete. An alphanumeric code was applied to each of these classes, and (b) four prognostic codes, related to age, timing, techniques, and comorbidities., Results: An alphanumeric code was produced, similar to that used in the AO classification of fractures., Conclusions: The authors propose this novel classification for PNIs, with the main advantage to allow physicians to easily understand the characteristics of nerve lesions, severity, possibility of spontaneous recovery, onset of early complications, need for surgical treatment, and the best surgical approach., Level of Evidence: according to the Oxford 2011 level of evidence, level 2., (© 2023. The Author(s).)

Background: To identify the rate of 30-day complications after primary repair of upper extremity peripheral nerve injuries, associated diagnoses, and postoperative complication rate., Methods: The American College of Surgeons National Surgical Quality Improvement Program database was reviewed from 2010 to 2016. Current Procedural Terminology codes consistent with primary nerve repair of the upper extremity were identified and included in the analysis. Patient demographics, comorbidities, type of procedure (elective/emergent), wound class, operative time, and 30-day complications were recorded. Patients with isolated upper extremity nerve injuries (isolated) were compared with those with peripheral nerve injuries in addition to bone, tendon, or soft tissue injuries (multiple)., Results: In all, 785 patients were identified as having upper extremity nerve repairs (0.16%). Of them, 64% were men and 36% were women; the average patient age was 40 years. The most common indication for surgery was injury to the digits (54% of cases). Thirty-day adverse events occurred in 3% of all cases. Isolated nerve injury occurred in 43% of patients, whereas 57% had additional injuries. The multiple injury group had a significantly higher complication rate compared with the isolated group (1% vs 4.5%) ( P = .007). Repair of tendon at forearm or wrist was the most common concurrent procedure performed., Conclusions: Thirty-day complications among upper extremity peripheral nerve injuries are low, accounting for 3% of cases. Return to the operating room accounted for nearly half of all complications. Patients in the multiple injury group accounted for more than half of these and had a significantly higher complication rate compared with patients with isolated nerve injuries.

Peripheral Nerve Injuries (PNI) affect more than 20 million Americans and severely impact quality of life by causing long-term disability. PNI is characterized by nerve degeneration distal to the site of nerve injury resulting in long periods of skeletal muscle denervation. During this period, muscle fibers atrophy and frequently become incapable of "accepting" innervation because of the slow speed of axon regeneration post injury. We hypothesize that reprogramming the skeletal muscle to an embryonic-like state may preserve its reinnervation capability following PNI. To this end, we generate a mouse model in which NANOG, a pluripotency-associated transcription factor is expressed locally upon delivery of doxycycline (Dox) in a polymeric vehicle. NANOG expression in the muscle upregulates the percentage of Pax7+ nuclei and expression of eMYHC along with other genes that are involved in muscle development. In a sciatic nerve transection model, NANOG expression leads to upregulation of key genes associated with myogenesis, neurogenesis and neuromuscular junction (NMJ) formation. Further, NANOG mice demonstrate extensive overlap between synaptic vesicles and NMJ acetylcholine receptors (AChRs) indicating restored innervation. Indeed, NANOG mice show greater improvement in motor function as compared to wild-type (WT) animals, as evidenced by improved toe-spread reflex, EMG responses and isometric force production. In conclusion, we demonstrate that reprogramming muscle can be an effective strategy to improve reinnervation and functional outcomes after PNI., (© 2024. The Author(s).)

Background: Peripheral nerve injuries are severe conditions with potential lifelong impairment, which is especially meaningful for the pediatric population. Knowledge on prevalence, injury mechanisms and concomitant injuries is, therefore, of utmost importance to increase clinician awareness and enable early diagnosis and treatment. As current literature on pediatric nerve lesions and concomitant injuries is scarce, we aimed to analyze all details of our patient population., Methods: A total of 110 667 patients treated at our level 1 trauma center from 2012 to 2021 were evaluated for pediatric peripheral nerve injuries, causes, concomitant injuries and assessed for lesion classification (in continuity, partial lesion, dissection) and further relevant intraoperative findings., Results: We found 5026 patients of all ages with peripheral nerve lesions, whereof 288 were pediatric, resulting in a prevalence of 5.7% of pediatric patients with nerve injuries. Mean age was 12.4 ± 4.6 years. Most common lesions were digital nerves (48.2%), followed by median (14.9%), ulnar (14.6%), radial (8.8%), peroneal nerve (5.2%) and brachial plexus injuries (2.1%). Of all pediatric nerve injuries, 3.8% were iatrogenic, only 30.2% had preserved continuity and 47.3% a concomitant vessel injury. Fractures were accompanied in 22.6%., Discussion: We observed that a large proportion of injures had complete transections, often accompanied by concomitant vessel injuries especially in distally located injuries, highlighting the importance of early surgical exploration. Radial, ulnar and lower extremity nerve injuries were often associated with fractures. Early surgical nerve repair is key to improve motor and sensory outcomes. Knowledge on mechanisms and concomitant injuries facilitates timely diagnosis and treatment, thereby potentially preventing lifelong impairment., (© 2023. The Author(s).)

Peripheral nerve injuries requiring surgical repair affect over 100,000 individuals in the US annually. Three accepted methods of peripheral repair include end-to-end, end-to-side, and side-to-side neurorrhaphy, each with its own set of indications. While it remains important to understand the specific circumstances in which each method is employed, a deeper understanding of the molecular mechanisms underlying the repair can add to the surgeon's decision-making algorithm when considering each technique, as well as help decide nuances in technique such as the need for making epineurial versus perineurial windows, length and dept of the nerve window, and distance from target muscle. In addition, a thorough knowledge of individual factors that are active in a particular repair can help guide research into adjunct therapies. This paper serves to summarize the similarities and divergences of the three commonly used nerve repair strategies and the scope of molecular mechanisms and signal transduction pathways in nerve regeneration as well as to identify the gaps in knowledge that should be addressed if we are to improve clinical outcomes in our patients.

Abstract Background Traumatic spinal cord and peripheral nerve injuries may lead to neurological deficits and fatal consequences. This study aimed to evaluate the characteristics of traumatic spinal cord and peripheral nerve injuries, examine the relationship between the type of injury and the affected nerves, and discuss appropriate prevention measures. Results Of these, 236 were males and 63 were females, and the mean age was 35.56 ± 15.10 years. Traffic accidents (56.9%) were the most common etiological factor. This study included 288 peripheral nerve injuries and 82 spinal cord injuries. The fibular nerve (n = 49) and cervical spinal cord (n = 35) were the most frequently injured areas. Permanent functional and sensorial losses associated with traumatic nerve injuries were observed in 239 (79.9%) cases, of which 171 exhibited loss of muscle strength, 114 presented with neuro-sensorial symptoms, 37 had urinary/faecal incontinence, and 1 demonstrated erectile dysfunction. And, the incidence of permanent loss of function was significantly higher following traffic accidents ( $$\chi$$ χ 2 = 50.095, Adj. p

Background: Peripheral nerve injuries are one of the most common and costly injuries especially in the young population. In this study, it is aimed to determine the histological role of epidermal growth factor (EGF) in nerve regeneration with an acute damage made on sciatic nerve in the rabbit model., Methods: We used 18 New Zealand rabbits (nine in control group and nine in experimental group). Each group was divided into two groups consisting of five rabbits planned for diameter measurement and four rabbits planned for spatial measurement. The sciatic nerve exploration in the right flank of each animal, full-thickness nerve damage, and then epineural repair was made by a single researcher. 10 µg/kg EGF was given to the repair area of the experimental group and five more EGF injections were given to the experimental group every other day postoperatively. In the control group, we used saline solution. Rabbits were observed for 8 weeks. During follow-up, two rabbits died. At the end of 8 weeks, the nerve tissue of each animal was evaluated histologically and morphologically., Results: In the experimental group consisting of five rabbits, the mean thickness of connective tissue (epineurium+ mesoneurium) was 156,867 µm; while, in the control group, the thickness was 25,170 µm. In the other groups, the numerical increase in epineurium and mesoneurium areas was detected in the EGF (+) group as a result of the comparative spatial measurements. Epineurium and mesoneurium enlargement was observed in the EGF-given group. Adipocyte and capillary increase was observed in connective tissue., Conclusion: EGF increases epineurium and mesoneurium diameters in peripheral connective tissue in acute peripheral nerve injury regeneration. However, further studies are needed to understand this effect clinically and physiologically.

We diagnosed 66 peripheral nerve injuries in 34 patients who survived severe coronavirus disease 2019 (COVID-19). We combine this new data with published case series re-analyzed here (117 nerve injuries; 58 patients) to provide a comprehensive accounting of lesion sites. The most common are ulnar (25.1%), common fibular (15.8%), sciatic (13.1%), median (9.8%), brachial plexus (8.7%) and radial (8.2%) nerves at sites known to be vulnerable to mechanical loading. Protection of peripheral nerves should be prioritized in the care of COVID-19 patients. To this end, we report proof of concept data of the feasibility for a wearable, wireless pressure sensor to provide real time monitoring in the intensive care unit setting., (© 2022. The Author(s).)

Purpose: Peripheral nerve injuries can lead to lasting functional impairments, impacting movement and quality of life. FK-506, a widely used immunosuppressant, has demonstrated potential in promoting nerve regeneration in addition to its immunosuppressive effects. This study investigates the use of a local reservoir flap to deliver FK-506 directly to the nerve injury site, aiming to enhance nerve regeneration while minimizing systemic immunosuppression., Materials and Methods: Sciatic nerve injuries were surgically induced in 24 rats, which were divided into control, 0.5 mg/kg FK-506 (Exp 1), and 2.0 mg/kg FK-506 (Exp 2) groups. A superficial inferior epigastric artery flap served as a reservoir for FK-506, allowing direct delivery to the injury site. FK-506 was administered intermittently over a 4-week period. Outcomes included the Sciatic Functional Index (SFI), muscle recovery (width and weight), nerve morphology, expression of neurogenic markers such as GDNF, immune cell counts, and body weight., Results: Exp 1 (0.5 mg/kg) demonstrated significant improvements in SFI, GDNF expression, and muscle width compared to the control and high-dose groups. These findings suggest that FK-506 administration via a reservoir flap, particularly at a lower dose, supports effective nerve regeneration. Additionally, FK-506 treatment did not result in significant changes in immune cell profiles or body weight, indicating minimal systemic effects., Conclusion: Localized FK-506 administration via a reservoir flap effectively enhances peripheral nerve regeneration and minimizes systemic immunosuppression, making it a promising approach for clinical application in treating peripheral nerve injuries., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Neurotrauma in limbs can induce sustained neuroinflammation, resulting in persistent disruption of nerve tissue architecture and retardation of axon regrowth. Despite macrophage-mediated inflammation promoting the removal of necrotic neural components and stimulating neo-vessel ingrowth, detrimental shifts in macrophage phenotype exacerbate nerve degeneration. Herein, we find that peripheral nerve injuries (PNIs) result in abundant secreted frizzled-related protein 1 (sFRP1) expression, particularly by Schwann cells (SCs). Heat shock protein 90 (HSP90) in macrophages recognizes sFRP1 and triggers a dysregulated secretion of inflammatory mediators. Single-cell atlas of human injured peripheral nerves reveals the appearance of sFRP1-expressing SCs with mesenchymal traits and macrophages with a proinflammatory genetic profile. Deletion of either SC-specific sFRP1 or macrophage-specific HSP90 alleviates neuroinflammation and prevents the progression of nerve degeneration. Together, our findings implicate the response of macrophages to SC-derived sFRP1 in exacerbating nerve damage following PNIs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Tau is a microtubule-associated protein that plays a vital role in the mammalian nervous system. Alternative splicing of the MAPT gene leads to the formation of tau isoforms with varying N-terminal inserts and microtubule-binding repeats. Dysregulation of tau alternative splicing has been linked to diseases in the central nervous system, but the roles of tau isoforms in the peripheral nervous system remain unclear. Here, we investigated the alternative splicing of tau exons 4A and 10 in the sciatic nerve and Schwann cells during development and following injury. We discovered that low-molecular-weight (LMW) tau, resulting from the exclusion of exon 4A, and 3R tau, generated by the exclusion of exon 10, diminishes with aging in rat sciatic nerve and Schwann cells. High-molecular-weight (HMW) tau and 3R tau increase in the adult sciatic nerve post-injury. We constructed viruses that expressed HMW-4R, LMW-4R, HMW-3R, and LMW-3R and introduced them into cultured cells or the distal part of the injured sciatic nerve to assess their effects on Schwann cell migration and proliferation. We also examined the effects of the four isoforms on axon growth and debris clearance after sciatic nerve injury. Our results demonstrated that tau isoforms inhibit Schwann cell proliferation while promoting Schwann cell migration and sciatic nerve regeneration. Specifically, the 3R-tau isoforms were more effective than the 4R-tau isoforms in promoting nerve regeneration. In conclusion, our study reveals the roles of tau isoforms in the peripheral nervous system and provides insights into the development of new therapeutic strategies for peripheral nerve injuries.

Peripheral nerve injury triggers rapid microglial activation, promoting M1 polarization within the spinal cord, which exacerbates the progression of neuropathic pain. C1q/TNF-related protein 9 (CTRP9), an adiponectin homolog, is known to suppress macrophage activation and exhibit anti-inflammatory properties through the activation of adiponectin receptor 1 (AdipoR1) in various disease contexts. Nevertheless, the involvement of CTRP9 in microglial polarization in the context of neuropathic pain is still unclear. Our study aimed to how CTRP9 influences spinal microglial polarization, neuroinflammation, and pain hypersensitivity, as well as the underlying mechanism, using a neuropathic pain model in male mice with spared nerve injury (SNI) of sciatic nerve. Our findings revealed SNI elevated the spinal CTRP9 and AdipoR1 levels in microglia. Furthermore, intrathecal administration of recombinant CTRP9 (rCTRP9) substantially weakened mechanical hypersensitivity and heat-related pain response triggered by SNI. On the other hand, rCTRP9 mediated a phenotypic switch in microglia, from the pro-inflammatory M1 state to the anti-inflammatory M2 state, by influencing the spinal AMPK/NF-κB mechanism in SNI mice. Additionally, treatment with AdipoR1 siRNA or an AMPK-specific antagonist both reversed the effects of CTRP9 on the phenotypic switching of spinal microglia and pain hypersensitivity. Collectively, these results indicate that CTRP9 ameliorates mechanical hypersensitivity and heat-related pain response, shifted the balance of microglia towards the anti-inflammatory M2 state, and suppresses neuroinflammatory responses by modulating the AMPK/NF-κB pathway, mediated by AdipoR1 activation, in mice with SNI., (© 2024. The Author(s).)

Neuropathic pain is characterised by periodic or continuous hyperalgesia, numbness, or allodynia, and results from insults to the somatosensory nervous system. Peripheral nerve injury induces transcriptional reprogramming in peripheral sensory neurons, contributing to increased spinal nociceptive input and the development of neuropathic pain. Effective treatment for neuropathic pain remains an unmet medical need as current therapeutics offer limited effectiveness and have undesirable effects. Understanding transcriptional changes in peripheral nerve injury-induced neuropathy might offer a path for novel analgesics. Our literature search identified 65 papers exploring transcriptomic changes post-peripheral nerve injury, many of which were conducted in animal models. We scrutinize their transcriptional changes data and conduct gene ontology enrichment analysis to reveal their common functional profile. Focusing on genes involved in 'sensory perception of pain' (GO:0019233), we identified transcriptional changes for different ion channels, receptors, and neurotransmitters, shedding light on its role in nociception. Examining peripheral sensory neurons subtype-specific transcriptional reprograming and regeneration-associated genes, we delved into downstream regulation of hypersensitivity. Identifying the temporal program of transcription regulatory mechanisms might help develop better therapeutics to target them effectively and selectively, thus preventing the development of neuropathic pain without affecting other physiological functions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Peripheral nerve injuries (PNIs) are common and devastating. The current standard of care relies on the slow and inefficient process of nerve regeneration after surgical intervention. Electrical stimulation (ES) has been shown to both experimentally and clinically result in improved regeneration and functional recovery after PNI for motor and sensory neurons; however, its effects on sympathetic regeneration have never been studied. Sympathetic neurons are responsible for a myriad of homeostatic processes that include, but are not limited to, blood pressure, immune response, sweating, and the structural integrity of the neuromuscular junction. Almost one quarter of the axons in the sciatic nerve are from sympathetic neurons, and their importance in bodily homeostasis and the pathogenesis of neuropathic pain should not be underestimated. Therefore, as ES continues to make its way into patient care, it is not only important to understand its impact on all neuron subtypes, but also to ensure that potential adverse effects are minimized. This piece gives an overview of the effects of ES in animals models and in humans while offering a perspective on the potential effects of ES on sympathetic axon regeneration.

Background/Aims:Due to the prioritization of limb and life-saving efforts by medical teams, peripheral nerve injuries (PNIs) resulting from earthquakes are frequently overlooked or receive delayed treatment. Thus, we examined earthquake-related PNIs in terms of their descriptive characteristics and injury patterns Methods: The study was conducted retrospectively in a tertiary hospital after Kahramanmaraş Earthquakes. The study included victims under rubble admitted to the hospital and diagnosed with PNI according to their medical records between 06 February and 28 February 2023. Results: The study included 70 patients and a total of 98 limbs with PNIs, with a mean patient age of 22.31±14.91 years. 77.6% (n=76) of PNIs involved the lower limb (68 peroneal and 8 sciatic nerves) and 22.4% (n=22) of PNIs involved the upper limbs (14 radial nerves, 5 ulnar nerves, 2 median nerves, 1 brachial plexus). It was found that 45.9% of PNIs (n=45) occurred in the right and 54.1% (n=53) in the left extremities. The median time under the rubble of the patients was 15 hours (IQR 8.75 - 32 hours). Fasciotomy was treated in 54.1% (n=43) of the extremities with PNI. Fasciotomies were most commonly performed on the cruris (42.9%), foot (26.5%), and thigh (16.3%). Conclusion: This study found that PNIs occurred most frequently in the lower limbs, compared with the upper limbs, among earthquake victims with CLIs. Lower limb PNIs mainly occurred in the peroneal nerve, while upper limb PNIs mainly occurred in the radial nerve.

Abstract Background Peripheral nerve injuries (PNI) have been associated with prone positioning (PP) in mechanically ventilated (MV) patients with COVID-19 pneumonia. The aims of this retrospective study were to describe PNI prevalence 3 months (M3) after intensive care unit (ICU) discharge, whether patients survived COVID-19 or another critical illness, and to search for risk factors of PNI. Results A total of 55 COVID (62 [54–69] years) and 22 non-COVID (61.5 [48–71.5] years) patients were followed at M3, after an ICU stay of respectively 15 [9–26.5] and 13.5 [10–19.8] days. PNI symptoms were reported by 23/55 (42.6%) COVID-19 and 8/22 (36%) non-COVID-19 patients (p = 0.798). As the incidence of PNI was similar in both groups, the entire population was used to determine risk factors. The MV duration predicted PNI occurrence (OR (CI95%) = 1.05 (1.01–1.10), p = 0.028), but not the ICU length of stay, glucocorticoids, or inflammation biomarkers. Conclusion In the present cohort, PNI symptoms were reported in at least one-third of the ICU survivors, in similar proportion whether patients suffered from severe COVID-19 or not.

This study aimed to investigate the therapeutic potential of human adipose-derived mesenchymal stem cells (hADSCs) modified with recombinant adeno-associated virus (rAAV) carrying the vascular endothelial growth factor 165 (VEGF165) gene in peripheral nerve injury (PNI). The hADSCs were categorized into blank, control (transduced with rAAV control vector), and VEGF165 (transduced with rAAV VEGF165 vector) groups. Subsequently, Schwann cell differentiation was induced, and Schwann cell markers were assessed. The sciatic nerve injury mouse model received injections of phosphate-buffered saline (PBS group), PBS containing hADSCs (hADSCs group), rAAV control vector (control-hADSCs group), or rAAV VEGF165 vector (VEGF165-hADSCs group) into the nerve defect site. Motor function recovery, evaluated through the sciatic function index (SFI), and nerve regeneration, assessed via toluidine blue staining along with scrutiny of Schwann cell markers and neurotrophic factors, were conducted. Modified hADSCs exhibited enhanced Schwann cell differentiation and elevated expression of Schwann cell markers [S100 calcium-binding protein B (S100B), NGF receptor (NGFR), and glial fibrillary acidic protein (GFAP)]. Mice in the VEGF165-hADSCs group demonstrated improved motor function recovery compared to those in the other three groups, accompanied by increased fiber diameter, axon diameter, and myelin thickness, as well as elevated expression of Schwann cell markers (S100B, NGFR, and GFAP) and neurotrophic factors [mature brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF)] in the distal nerve segment. rAAV-VEGF165 modification enhances hADSC potential in PNI, promoting motor recovery and nerve regeneration. Elevated Schwann cell markers and neurotrophic factors underscore therapy benefits, providing insights for nerve injury strategies., (© 2024 The Author(s). The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Introduction: The current study focuses on understanding the functional role of different subsets of endoneurial macrophages in autoimmune polyneuropathies (AP) and traumatic peripheral nerve injury (TPNI), which holds potential for clinical application. Recent studies have advanced our understanding of the diverse origins of macrophages within peripheral nerves. However, there remains a gap in our knowledge regarding how endoneurial macrophages from different origins affect disease progression in AP versus TPNI., Methods: Flow cytometry was utilized to analyze macrophage phenotypes, including polarization states, cytokine production, and myelin phagocytosis in animal models of AP and TPNI. This study focuses on two distinct origins of macrophages, namely CD11b + F4/80 hi tissue-resident (TRM) and CD11b + F4/80 int blood-derived macrophages (BDM). The study utilized two animal models: the first was the spontaneous autoimmune peripheral polyneuropathy (SAPP) model in B7.2-null non-obese diabetic (NOD-B7.2-/-) mice, which serves as a model for inflammatory demyelinating polyneuropathy; the second model involved wild type C57BL/6 mice subjected to sciatic nerve crush injury, modeling TPNI. Behavioral, electrophysiological, and histological analyses were performed to assess peripheral nerve injury., Results: The study found that pro-inflammatory M1 macrophage polarization and tumor necrosis factor-alpha production by macrophages were more pronounced in the peripheral nerves of SAPP mice compared to those with TPNI, with the majority of these macrophages being TRM. In contrast, endoneurial macrophages in mice with TPNI were mainly BDM, exhibiting a less defined macrophage polarization and cytokine profile than TRM in AP mice. Interestingly, myelin phagocytosis was primarily driven by BDM in both SAPP and TPNI mice., Discussion: This study offers novel insights into origin-dependent macrophage functions in AP and TPNI. Furthermore, these findings may help the future development of novel therapies targeting macrophage subsets of specific origin in AP and TPNI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sprenger-Svačina, Svačina, Gao, Ritzel, McCullough, Sheikh and Zhang.)

Peripheral nerve injuries lead to severe functional impairments, with rodent models essential for studying regeneration. This review examines key factors affecting outcomes. Age-related declines, like reduced nerve fiber density and impaired axonal transport of vesicles, hinder recovery. Hormonal differences influence regeneration, with BDNF/trkB critical for testosterone and nerve growth factor for estrogen signaling pathways. Species and strain selection impact outcomes, with C57BL/6 mice and Sprague-Dawley rats exhibiting varying regenerative capacities. Injury models - crush for early regeneration, chronic constriction for neuropathic pain, stretch for traumatic elongation and transection for severe lacerations - provide insights into clinically relevant scenarios. Repair techniques, such as nerve grafts and conduits, show that autografts are the gold standard for gaps over 3 cm, with success influenced by graft type and diameter. Time course analysis highlights crucial early degeneration and regeneration phases within the first month, with functional recovery stabilizing by three to six months. Early intervention optimizes regeneration by reducing scar tissue formation, while later interventions focus on remyelination. Understanding these factors is vital for designing robust preclinical studies and translating research into effective clinical treatments for peripheral nerve injuries.

Animal models of peripheral nerve injury (PNI) serve as the fundamental basis for the investigations of nerve injury, regeneration, and neuropathic pain. The injury properties of such models, including the intensity and duration, significantly influence the subsequent pathological changes, pain development, and therapeutic efficacy. However, precise control over the intensity and duration of nerve injury remains challenging within existing animal models, thereby impeding accurate and comparative assessments of relevant cases. Here, a new model that provides quantitative and off-body controllable injury properties via a magnetically controlled clamp, is presented. The clamp can be implanted onto the rat sciatic nerve and exert varying degrees of compression under the control of an external magnetic field. It is demonstrated that this model can accurately simulate various degrees of pathology of human patients by adjusting the magnetic control and reveal specific pathological changes resulting from intensity heterogeneity that are challenging to detect previously. The controllability and quantifiability of this model may significantly reduce the uncertainty of central response and inter-experimenter variability, facilitating precise investigations into nerve injury, regeneration, and pain mechanisms., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Peripheral nerve injury (PNI) poses a significant public health issue, often leading to muscle atrophy and persistent neuropathic pain, which can drastically impact the quality of life for patients. Electrical stimulation represents an effective and non-pharmacological treatment to promote nerve regeneration. Yet, the postoperative application of electrical stimulation remains a challenge. Here, we propose a fully biodegradable, self-powered nerve guidance conduit (NGC) based on dissolvable zinc-molybdenum batteries. The conduit can offer topographic guidance for nerve regeneration and deliver sustained electrical cues between both ends of a transected nerve stump, extending beyond the surgical window. Schwann cell proliferation and adenosine triphosphate (ATP) production are enhanced by the introduction of the zinc-molybdenum batteries. In rodent models with 10-mm sciatic nerve damage, the device effectively enhances nerve regeneration and motor function recovery. This study offers innovative strategies for creating biodegradable and electroactive devices that hold important promise to optimize therapeutic outcomes for nerve regeneration., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The incidence of peripheral nerve injury (PNI) in China is continuously increasing. With an inability to function due to sensory and motor abnormalities, patients with PNI suffer from neuropathic pain and subsequent lesions. Presently, effective treatments for PNI are limited. To determine the role of neuroprotectin D1 (NPD1) in PNI, a sciatic nerve crush injury model was developed to investigate the impact of NPD1 on sensory and motor function recovery following nerve injury. The results demonstrated that NPD1 administered at different time points might reduce mechanical allodynia and thermal hyperalgesia caused by PNI, and its analgesic effect was not tolerated. Immunohistochemistry analyses revealed that administering NPD1 to PNI mice decreased the spinal microglia and astrocyte activation and decreased the inflammatory factor expression in the spinal dorsal horn. Furthermore, NPD1 can inhibit the invasion of IBA-1 + macrophages in dorsal root ganglions generated by nerve injury. Meanwhile, it can help rehabilitate motor and neuromuscular functions following PNI. The results indicate that NPD1 may be involved in the sensory and motor function recovery following PNI., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Yu Tian et al.)

To explore a method to identify the sensory and motor fascicles of the peripheral nerve to achieve accurate peripheral nerve functional fascicle suture. The peripheral nerve Sunderland V injury model, muscle branch of the femoral nerve and saphenous nerve were established in the bilateral femoral nerves of Sprague-Dawley (SD) rats. The specific samples were grouped as follows: the main trunk of the femoral nerve was exposed bilaterally and cut with microscopic scissors in the main trunk of the femoral nerve to prepare a model of Sunderland V injury in the mixed fascicle of peripheral nerves; the muscle branch of the femoral nerve was exposed bilaterally and cut in the middle section of the muscle branch of the femoral nerve to prepare a model of Sunderland V injury in the motor fascicle of peripheral nerves; the saphenous nerve was exposed bilaterally and cut at 1 cm below the patella to prepare a model of Sunderland V injury to the sensory fascicle of the peripheral nerves. A carbon quantum dot (CD)-annexin V antibody complex was prepared and applied to the distal and proximal nerve stumps of the peripheral nerve Sunderland V injury model groups of SD rats. Under the excitation light source of a 380 nm uv lamp, fluorescence color development was observed under a fluorescence microscope after 5, 10, 15, and 20 min. At 5 min, sections of the bilateral femoral nerve trunk, muscular branches of the femoral nerve, and Sunderland V lesion of the saphenous nerve in SD rats were only dark in color under the microscope, and there was no difference in fluorescence. The intensity of the staining increased significantly for 10-20 min. The sensory fascicles and saphenous nerves of the femoral nerve trunk showed blue fluorescence under the CD-Annexin V antibody complex staining, while the motor fascicles and muscle branches of the femoral nerve trunk showed no fluorescence. Fluorescence intensity gradually decreased after 20 min of staining. There was no significant difference in the staining intensity at 5, 10, 15, and 20 min in each group. Our results suggest that the CD-Annexin antibody complex can be used to identify functional fascicles of peripheral nerves in SD rats., (© 2024. The Author(s).)

The anterior cingulate cortex (ACC) is one of the critical brain areas for processing noxious information. Previous studies showed that peripheral nerve injury induced broad changes in the ACC, contributing to pain hypersensitivity. The neurons in layer 3 (L3) of the ACC receive the inputs from the mediodorsal thalamus (MD) and form the feedforward inhibition (FFI) microcircuits. The effects of peripheral nerve injury on the MD-driven FFI in L3 of ACC are unknown. In our study, we record the enhanced excitatory synaptic transmissions from the MD to L3 of the ACC in mice with common peroneal nerve ligation, affecting FFI. Chemogenetically activating the MD-to-ACC projections induces pain sensitivity and place aversion in naive mice. Furthermore, chemogenetically inactivating MD-to-ACC projections decreases pain sensitivity and promotes place preference in nerve-injured mice. Our results indicate that the peripheral nerve injury changes the MD-to-ACC projections, contributing to pain hypersensitivity and aversion., (© 2024. The Author(s).)

One of the major challenges in the development of a larger and longer nerve conduit for peripheral nerve repair is the limitation in oxygen and nutrient diffusion within the tissue after transplantation preventing Schwann cell and axonal migration. This restriction is due to the slow neovascularization process of the graft starting from both nerve endings. To overcome this limitation, we propose the design of a living tissue-engineered nerve conduit made of an internal tube with a three-dimensional structure supporting axonal migration, which is inserted inside a hollow external tube that plays the role of an epineurium and is strong enough to be stitched to the severed nerve stumps. The internal tube is made of a rolled living fibroblast sheet and can be seeded with endothelial cells to promote the formation of a network containing capillary-like structures which allow rapid inosculation with the host nerve microvasculature after grafting. Human nerve conduits were grafted in immunodeficient rats to bridge a 15 mm sciatic nerve gap. Human capillaries within the pre-vascularized nerve conduit successfully connected to the host circulation 2 weeks after grafting. Twenty-two weeks after surgery, rats transplanted with the nerve conduits had a similar motor function recovery compared to the autograft group. By promoting rapid vascularization of the internal nerve tube from both ends of the nerve stumps, this endothelialized nerve conduit model displays a favorable environment to enhance axonal migration in both larger caliber and longer nerve grafts., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aim: to analyze modern professional literature and summarize data on treatment methods for peripheral nerve injuries, taking into account the mechanisms of positive effects. The article presents an overview of possible methods for treatment of peripheral nerve injuries, fundamental classifications of peripheral nerve injuries, their differences are considered, pathophysiological mechanisms and the probability of spontaneous recovery depending on the degree of injury, general principles and conditions for successful regeneration of the peripheral nerve. Options, combinations, advantages and disadvantages of such surgical methods for peripheral nerve injury treatment as neurorrhaphy, autotransplantation and allotransplantation are described in detail, such terms as “small”, “large” and “critical” gaps between the nerve stumps are specified. Classifications and characteristics of conduits are described, types of synthetic conduits are considered. The use of drugs, Schwann cells, growth and neurotrophic factors, neural, embryonic and mesenchymal stem cells of various origins, exosomes of mesenchymal stem cells in the so-called “stem cell-free therapy” in treating this pathology is mentioned. Genetically modified mesenchymal stem cells, optokinetics are also noted, such physical methods for peripheral nerve injury treatment as short-term low-frequency electrical stimulation of the nerve, magnetic stimulation, low-intensity ultrasound, photobiomodulation therapy, photochemical bonding are discussed, indicating some mechanisms of their positive effects. Conclusions. Improving the quality of life and reducing the degree of disability in patients with injuries of the main nerve trunks depends on the combined use of a number of surgical, bioengineering and regenerative technologies. These involve the restoration of the anatomical continuity of the nerve, including through the use of natural or artificial elements, cellular technologies and the management of regenerative processes. Therefore, every time, a surgeon is facing a major challenge to create a combination of various means from the indicated basic components for the treatment of nerve damage in managing a particular patient. However, such a treatment approach requires proper competences of surgeons as well as specific material and technical bases in order to bring down the level of social tension in patients with injuries of the main nerve trunks.

Abstract The management of peripheral nerve injuries is an important concern due to the their incidence of nerve lesions and inappropriate regeneration that follows severe injuries, which ultimately reduces the lives of patients with this condition. Different strategies have been investigated to repair severe nerve injuries with the improvement of motor and sensory regeneration. Although autograft remains the gold standard technique, an emerging number of research articles concerning nerve conduit use have been reported in the last few years. Nerve conduits aim to overcome autograft disadvantages, but they satisfy some requirements to be suitable for nerve repair. A universal ideal conduit does not exist since conduit properties have to be evaluated case by case; nevertheless, because of their high biocompatibility and biodegradability, natural‐based biomaterials have great potential to be used to produce nerve guides. Although they have many characteristics with synthetic biomaterials, natural‐based biomaterials are preferable because of their extraction sources; indeed, these biomaterials are obtained from different renewable sources or food waste, thus reducing environmental impact and enhancing sustainability in comparison to synthetic ones. This review highlights the recent progress in the development of natural‐based biomaterials and their derivatives for the management of peripheral nerve injuries.

IntroductionTraumatic peripheral nerve injuries pose significant challenges to healthcare systems and individuals, affecting sensory function, causing neuropathic pain, and impairing quality of life. Despite their impact, comprehensive studies on the epidemiology and regional variance of these injuries are scarce. Understanding the incidence, trends, and anatomical distribution of such injuries is essential for targeted interventions and resource allocation.MethodsThis observational study utilized register-based data from the Swedish National Patient Register covering the period from 2008 to 2022. Incidence rates, trends, and anatomical distribution of traumatic peripheral nerve injuries were analyzed using descriptive statistics, Poisson regression modeling, and regional comparisons.ResultsHigher incidences of peripheral nerve injuries were observed among men compared to women across all age groups. The hand and wrist were the most commonly affected sites. Regional variations in incidence rates were evident, with some regions consistently exhibiting higher rates compared to others. Notably, a decreasing trend in injuries was observed over the study period.ConclusionThis study underscores the importance of targeted interventions and preventive strategies, considering sex, age, and regional disparities. Further research incorporating individual patient-level data is warranted to enhance our understanding and inform tailored interventions to reduce the burden of these injuries.

Objectives : Vitamin B complexes are frequently used in clinical practice for peripheral nerve trauma. However, there is a lack of scientific data on their effectiveness. This study aims to investigate the impact of the vitamin B complex on nerve recovery in a rat model of peripheral nerve paralysis. Materials and Methods : Sixty male Wistar Albino rats were divided into six groups. Models of nerve injury, including blunt trauma, nerve incision, and autograft, were performed on all rats approximately 1 cm distal to the sciatic notch. B-complex vitamins were injected intraperitoneally at 0.2 mL/day to the treatment groups. The control groups were given 0.2 mL/day saline. After 1 month, the study was terminated, electromyography (EMG) was performed to measure the conduction velocity, and nerve tissue was taken from the repair line. The sciatic function indexes (SFIs) were calculated and analyzed. The histopathological samples were stained with hematoxylin and eosin and Toluidine blue and examined with a light microscope. Pathologically, myelination, fibrosis, edema, and mast cell densities in the nervous tissue were evaluated. Results : The vitamin B treatment groups demonstrated significant improvements in SFI compared to the control groups, indicating functional improvement in nerve damage ( p < 0.05). In the nerve graft group, the vitamin B group showed a shorter latency, higher velocity, and larger peak-to-peak compared to the controls ( p < 0.05). In the nerve transection group, the vitamin B group had better latency, velocity, and peak-to-peak values than the controls ( p < 0.05). In the crush injury group, the vitamin B group exhibited an improved latency, velocity, and peak-to-peak compared to the controls ( p < 0.05). Better myelination, less fibrosis, edema, and mast cells were also in the vitamin B group ( p < 0.05). Conclusions : Vitamin B treatment significantly improves nerve healing and function in peripheral nerve injuries. It enhances nerve conduction, reduces fibrosis, and promotes myelination, indicating its therapeutic potential in nerve regeneration.

Peripheral nerve injury (PNI) occurs due to damage of peripheral nerves, with healthcare professionals playing significant roles in PNI rehabilitation. This study aimed to explore the knowledge, attitudes, and practices (KAP) towards PNI rehabilitation among healthcare professionals. This cross-sectional study was conducted on June 2023 in China and healthcare professionals were enrolled. A total of 611 valid questionnaires were collected, with 62.52% female respondents. Mean scores for KAP were 14.26 ± 2.044 (possible range: 0-19), 29.77 ± 3.622 (possible range: 7-35), and 41.55 ± 9.523 (possible range: 11-55), respectively. Multivariate logistic regression revealed positive associations of professional titles (OR = 1.743, 95% CI: 1.083-2.804), occupation (OR = 1.833, 95% CI: 1.151-2.919), and involvement in treatment or care of PNI patients (OR = 1.462, 95% CI: 1.024-2.088) with knowledge. Knowledge (OR = 1.155, 95% CI: 1.042-1.280), gender (OR = 2.140, 95% CI: 1.255-3.646), education (OR = 2.258, 95% CI: 1.131-4.507), and involvement in treatment or care of PNI patients (OR = 2.463, 95% CI: 1.460-4.155) were positively associated with attitude. Attitude (OR = 1.214, 95% CI: 1.148-1.283), bachelor's degree education (OR = 0.548, 95% CI: 0.326-0.919), master's degree or higher (OR = 0.545, 95% CI: 0.308-0.964), having rehabilitation training for PNI (OR = 2.485, 95% CI: 1.633-3.781), and involvement in treatment or care of PNI patients (OR = 2.093, 95% CI: 1.395-3.138) were independently associated with practice. Healthcare professionals exhibited moderate knowledge, positive attitudes, and moderate practices towards the PNI rehabilitation. Those involved in the treatment or care of PNI have significantly higher KAP. Targeted interventions were needed to enhance understanding and promote proactive engagement in clinical practice., (© 2024. The Author(s).)

Purpose: Traumatic peripheral nerve injury (PNI), which occurs in up to 3% of trauma patients, is a devastating condition that often leads to permanent disability. However, knowledge of traumatic PNI is limited. We describe epidemiology and clinical characteristics of traumatic PNI in Korea and identify the predictors of traumatic complete PNI., Methods: A list of enlisted soldier patients who were discharged from military service due to PNI over a 10-year period (2012-2021) was obtained, and their medical records were reviewed. Patients were classified according to the causative events (traumatic vs. nontraumatic) and injury severity (complete vs. incomplete). Of traumatic PNIs, we compared the clinical variables between the incomplete and complete PNI groups and identified predictors of complete PNI., Results: Of the 119 young male patients who were discharged from military service due to PNI, 85 (71.4%) were injured by a traumatic event; among them, 22 (25.9%) were assessed as having a complete injury. The most common PNI mechanism (n=49, 57.6%), was adjacent fractures or dislocations. Several injury-related characteristics were significantly associated with complete PNI: laceration or gunshot wound, PNI involving the median nerve, PNI involving multiple individual nerves (multiple PNI), and concomitant muscular or vascular injuries. After adjusting for other possible predictors, multiple PNI was identified as a significant predictor of a complete PNI (odds ratio, 3.583; P=0.017)., Conclusions: In this study, we analyzed the characteristics of enlisted Korean soldiers discharged due to traumatic PNI and found that the most common injury mechanism was adjacent fracture or dislocation (57.6%). Patients with multiple PNI had a significantly increased risk of complete injury. The results of this study contribute to a better understanding of traumatic PNI, which directly leads to a decline in functioning in patients with trauma.

Aims: Right phrenic nerve (RPN) injury is a disabling but uncommon complication of atrial fibrillation (AF) radiofrequency ablation. Pace-mapping is widely used to infer RPN's course, for limiting the risk of palsy by avoiding ablation at capture sites. However, information is lacking regarding the distance between the endocardial sites of capture and the actual anatomic RPN location. We aimed at determining the distance between endocardial sites of capture and anatomic CT location of the RPN, depending on the capture threshold., Methods and Results: In consecutive patients undergoing AF radiofrequency ablation, we defined the course of the RPN on the electroanatomical map with high-output pacing at up to 50 mA/2 ms, and assessed RPN capture threshold (RPN-t). The true anatomic course of the RPN was delineated and segmented using CT scan, then merged with the electroanatomical map. The distance between pacing sites and the RPN was assessed. In 45 patients, 1033 pacing sites were analysed. Distances from pacing sites to RPN ranged from 7.5 ± 3.0 mm (min 1) when RPN-t was ≤10 mA to 19.2 ± 6.5 mm (min 9.4) in cases of non-capture at 50 mA. A distance to the phrenic nerve > 10 mm was predicted by RPN-t with a ROC curve area of 0.846 [0.821-0.870] (P < 0.001), with Se = 80.8% and Sp = 77.5% if RPN-t > 20 mA, Se = 68.0% and Sp = 91.6% if RPN-t > 30 mA, and Se = 42.4% and Sp = 97.6% if non-capture at 50 mA., Conclusion: These data emphasize the utility of high-output pace-mapping of the RPN. Non-capture at 50 mA/2 ms demonstrated very high specificity for predicting a distance to the RPN > 10 mm, ensuring safe radiofrequency delivery., Competing Interests: Conflict of interest: F.M.: consultant for Biosense-Webster and Abbott., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: A favorable regenerative microenvironment is essential for peripheral nerve regeneration. Neural tissue-specific extracellular matrix (ECM) is a natural material that helps direct cell behavior and promote axon regeneration. Both bone marrow-derived mesenchymal stem cells (BMSCs) and adipose-derived mesenchymal stem cells (ADSCs) transplantation are effective in repairing peripheral nerve injury (PNI). However, there is no study that characterizes the in vivo microenvironmental characteristics of these two MSCs for the early repair of PNI when combined with neural tissue-derived ECM materials, i.e., acellular nerve allograft (ANA)., Methods: In order to investigate biological characteristics, molecular mechanisms of early stage, and effectiveness of ADSCs- or BMSCs-injected into ANA for repairing PNI in vivo, a rat 10 mm long sciatic nerve defect model was used. We isolated primary BMSCs and ADSCs from bone marrow and adipose tissue, respectively. First, to investigate the in vivo response characteristics and underlying molecular mechanisms of ANA combined with BMSCs or ADSCs, eighty-four rats were randomly divided into three groups: ANA group, ANA+BMSC group, and ANA+ADSC group. We performed flow cytometry, RT-PCR, and immunofluorescence staining up to 4 weeks postoperatively. To further elucidate the underlying molecular mechanisms, changes in long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) were systematically investigated using whole transcriptome sequencing. We then constructed protein-protein interaction networks to find 10 top ranked hub genes among differentially expressed mRNAs. Second, in order to explore the effectiveness of BMSCs and ADSCs on neural tissue-derived ECM materials for repairing PNI, sixty-eight rats were randomized into four groups: ANA group, ANA+BMSC group, ANA+ADSC group, and AUTO group. In the ANA+BMSC and ANA+ADSC groups, ADSCs/BMSCs were equally injected along the long axis of the 10-mm ANA. Then, we performed histological and functional assessments up to 12 weeks postoperatively., Results: The results of flow cytometry and RT-PCR showed that ANA combined with BMSCs exhibited more significant immunomodulatory effects, as evidenced by the up-regulation of interleukin (IL)-10, down-regulation of IL-1β and tumor necrosis factor-alpha (TNF-α) expression, promotion of M1-type macrophage polarization to M2-type, and a significant increase in the number of regulatory T cells (Tregs). ANA combined with ADSCs exhibited more pronounced features of pro-myelination and angiogenesis, as evidenced by the up-regulation of myelin-associated protein gene (MBP and MPZ) and angiogenesis-related factors (TGF-β, VEGF). Moreover, differentially expressed genes from whole transcriptome sequencing results further indicated that ANA loaded with BMSCs exhibited notable immunomodulatory effects and ANA loaded with ADSCs was more associated with angiogenesis, axonal growth, and myelin formation. Notably, ANA infused with BMSCs or ADSCs enhanced peripheral nerve regeneration and motor function recovery with no statistically significant differences., Conclusions: This study revealed that both ANA combined with BMSCs and ADSCs enhance peripheral nerve regeneration and motor function recovery, but their biological characteristics (mainly including immunomodulatory effects, pro-vascular regenerative effects, and pro-myelin regenerative effects) and underlying molecular mechanisms in the process of repairing PNI in vivo are different, providing new insights into MSC therapy for peripheral nerve injury and its clinical translation., (© 2024. The Author(s).)

Peripheral nerve injury (PNI) is a complex and protracted process, and existing therapeutic approaches struggle to achieve effective nerve regeneration. Recent studies have shown that mesenchymal stem cells (MSCs) may be a pivotal choice for treating peripheral nerve injury. MSCs possess robust paracrine capabilities, and exosomes, as the primary secretome of MSCs, are considered crucial regulatory mediators involved in peripheral nerve regeneration. Exosomes, as nanocarriers, can transport various endogenous or exogenous bioactive substances to recipient cells, thereby promoting vascular and axonal regeneration while suppressing inflammation and pain. In this review, we summarize the mechanistic roles of exosomes derived from MSCs in peripheral nerve regeneration, discuss the engineering strategies for MSC-derived exosomes to improve therapeutic potential, and explore the combined effects of MSC-derived exosomes with biomaterials (nerve conduits, hydrogels) in peripheral nerve regeneration.

Peripheral nerve injury is a prevalent clinical problem that often leads to lifelong disability and reduced quality of life. Although peripheral nerves can regenerate, recovery after severe injury is slow and incomplete. The current gold standard treatment, autologous nerve transplantation, has limitations including donor site morbidity and poor functional outcomes, highlighting the need for improved repair strategies. We developed a reproducible in vitro hollow channel collagen gel construct to investigate peripheral nerve regeneration (PNR) by exploring the influence of key extracellular matrix (ECM) proteins on axonal growth and regeneration. Channels were coated with ECM proteins: collagen IV, laminin, or fibronectin and seeded with dorsal root ganglia (DRG) collected from E16 rat embryos to compare the ability of the ECM proteins to enhance axonal growth. Robust axonal extension and Schwann cell (SC) infiltration were observed in fibronectin-coated channels, suggesting its superiority over other ECM proteins. Differential effects of ECM proteins on axons and SCs indicated direct growth stimulation beyond SC-mediated guidance. In vitro laceration injury modeling further confirmed fibronectin's superior pro-regenerative effects, showcasing its potential in enhancing axonal regrowth post-injury. Advancing in vitro modeling that closely replicates native microenvironments will accelerate progress in overcoming the limitations of current nerve repair approaches., (© 2024. The Author(s).)

Berberine (BBR) has demonstrated potent anti-inflammatory effects by modulating macrophage polarization. Nevertheless, the precise mechanisms through which berberine regulates post-injury inflammation within the peripheral nerve system remain elusive. This study seeks to elucidate the role of BBR and its underlying mechanisms in inflammation following peripheral nerve injury (PNI). Adult male C57BL/6J mice subjected to PNI were administered daily doses of berberine (0, 60, 120, 180, 240 ​mg/kg) via gavage from day 1 through day 28. Evaluation of the sciatic function index (SFI) and paw withdrawal threshold revealed that BBR dose-dependently enhanced both motor and sensory functions. Immunofluorescent staining for anti-myelin basic protein (anti-MBP) and anti-neurofilament-200 (anti-NF-200), along with histological staining comprising hematoxylin-eosin (HE), luxol fast blue (LFB), and Masson staining, demonstrated that BBR dose-dependently promoted structural regeneration. Molecular analyses including qRT-PCR, Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence confirmed that inactivation of the NLRP3 inflammasome by MCC950 shifted macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, while also impeding macrophage infiltration. Furthermore, BBR significantly downregulated the expression of the NLRP3 inflammasome and its associated molecules in macrophages, thereby mitigating NLRP3 inflammasome activation-induced macrophage M1 polarization and inflammation. In summary, BBR's neuroprotective effects were concomitant with the suppression of inflammation after PNI, achieved through the inhibition of NLRP3 inflammasome activation-induced macrophage M1 polarization., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Iatrogenic nerve injuries can result from surgical damage. Thus, physicians should be aware of the risk factors and procedures that need to be followed in such patients. The purpose of this study was to examine data pertaining to patients with known iatrogenic nerve injuries and to elucidate the detailed causes of these injuries, the affected nerves, and the type of surgical procedures for treatment., Methods: This retrospective study included 232 consecutive patients who underwent surgical treatment for peripheral nerve palsy or nerve injury between 2006 and 2017 at our hospital. Among the 232 patients investigated, we identified 51 cases with iatrogenic nerve injuries (23 women and 28 men; mean age, 51.3 years). Among the 51 patients, 45 were referred from other hospitals, and the remaining were from our hospital. Data were summarized using descriptive statistics., Results: Direct surgical damage occurred in 94% (48/51) of patients with iatrogenic nerve injuries. Such injuries mostly developed after surgery for bone fractures (33%), resection of soft tissue tumors (22%), and carpal tunnel release procedures (20%). The nerves most commonly affected in such procedures are the radial nerve (26%), median nerve (24%), and ulnar nerve (17%). The median interval of referral to our hospital after nerve injury was 5.1 months. The median interval of surgery to correct the injury was 7 months. Surgeries to correct iatrogenic nerve injuries performed at our hospital included neurolysis (55%), nerve grafts (29%), direct suture procedures (10%), and tendon transfers (6%)., Conclusions: We believe that wide dissemination of the results obtained in this study will reduce the incidence of iatrogenic peripheral nerve injuries and increase the speed of referrals to specialized centers., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)