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Objective: An altered sensation during endodontic treatment can occur due to the extrusion of endodontic materials. This study aims to discuss intentional replantation to address paresthesia resulting from an endodontic file penetrating the inferior alveolar nerve canal and provide a protocol for managing nerve injuries in such incidents. Case presentation: A 12-year-old girl developed paresthesia when an endodontic file separated and was inadvertently pushed through the apical foramen into the inferior alveolar nerve canal during root canal treatment of the mandibular left first molar. A CBCT scan revealed the file penetrating the canal towards the inferior border of the mandible. After considering the treatment options, intentional replantation was deemed suitable. The tooth was atraumatically extracted and preserved in sterile saline. The surgeon then carefully cleaned and irrigated the socket. The radiographic assessment confirmed successful file removal from the socket. The root ends were resected, and retrograde preparation and obturation were conducted using ultrasonic tips and mineral trioxide aggregate. The tooth was then replanted into the socket. Successful replantation was confirmed by tooth stability and an audible click. The patient was prescribed antibiotics and steroids. After completion of the endodontic treatment, a stainless steel crown was cemented. The successful intentional replantation procedure resulted in rapid improvement in the patient's condition. The normal sensation had been restored, indicating nerve recovery. At the 15-month follow-up, periapical bone healing and the eruption of the adjacent second molar were observed, affirming the treatment protocol's overall success. Conclusion: Prompt intervention and immediate intentional replantation facilitated direct inspection of the separated file within the socket. Collaboration between an oral maxillofacial surgeon and an endodontist ensures expedited and targeted treatment, leading to favorable outcomes. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Tissue Engineering Research / Zhongguo Zuzhi Gongcheng Yanjiu is the property of Chinese Journal of Tissue Engineering Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Plastic Surgery is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background Deoxycholic acid (ATX-101) is a drug administered by subcutaneous injection for local fat reduction. However, ATX-101 treatment has been reported to cause marginal mandibular nerve injury with noticeable functional deficits when targeting submental fat. As a cytolytic agent with some selectivity for adipocytes, ATX-101 may damage the lipid-rich myelin surrounding peripheral nerves. Objectives The aim of this study was to characterize nerve injury caused by ATX-101 injection in an experimental rat sciatic nerve model. Methods Injuries to the sciatic nerve caused by intrafascicular and extrafascicular injections of ATX-101, and by lidocaine (positive control) and saline (negative control) injections, were compared. Nerves were harvested at a 2-week endpoint for histomorphometric analysis. Results The cross-sectional area of nerve injury was significantly increased by ATX-101 injection. The damaged areas amounted to 75% ± 15% with intrafascicular ATX-101 (P <.001), 41% ± 21% with extrafascicular ATX-101 (P <.01), and 38% ± 20% with positive-control lidocaine (P <.01), compared with 7% ± 13% with negative-control saline. Demyelinating injury was a significant mechanism of injury in the affected nerve fibers compared with uninjured nerve fibers (P <.04), but there was no difference in the axon-to-myelin area ratio between the lidocaine and ATX-101 cohorts. After 2 weeks, Wallerian degeneration was evident with only small regenerating nerve fibers present in the ATX-101-injured groups compared with saline (average fiber width, 2.54 ± 0.26 μm vs 5.03 ± 0.44 μm, P <.001). Conclusions ATX-101 can cause extensive nerve injury in rats. The mechanism of action for ATX-101 does not preferentially target myelin more than other common neurotoxic agents. Appropriate knowledge of surgical anatomy and injection technique is necessary for any practitioners administering ATX-101 injections. [ABSTRACT FROM AUTHOR]

Background: Advances in treatment philosophies and microsurgical techniques for peripheral nerve injuries (PNI) have led to improved outcomes. However, lack of standardisation in the evaluation of clinical outcomes after PNI treatment precludes the ability to compare reconstruction methods, such as nerve transfer, nerve grafting, free functioning muscle transfers and tendon transfers. To this end, our goal is to work collaboratively to establish a core outcome set to evaluate outcomes after PNI. Methods: The protocol for this arc of work, delineated in this manuscript, consists of two phases: (1) conducting a systematic review of how outcomes are currently reported following PNI and (2) a Delphi process to gain consensus on the measures to include in the core outcome set for PNI. In the Delphi process, two online rounds will be used to gather consensus on the importance of each outcome measure. A final round will be conducted in person to discuss and resolve measures for which there is not yet consensus and to finalise the core outcomes set. Conclusions: Through this process, a common standard for reporting outcomes after PNI will be created, facilitating collaboration and future research. [ABSTRACT FROM AUTHOR]

Neuropathic pain is a pervasive health concern worldwide, posing significant challenges to both clinicians and neuroscientists. While acute pain serves as a warning signal for potential tissue damage, neuropathic pain represents a chronic pathological condition resulting from injury or disease affecting sensory pathways of the nervous system. Neuropathic pain is characterized by long-lasting ipsilateral hyperalgesia (increased sensitivity to pain), allodynia (pain sensation in response to stimuli that are not normally painful), and spontaneous unprovoked pain. Current treatments for neuropathic pain are generally inadequate, and prevention remains elusive. In this review, we provide an overview of current treatments, their limitations, and a discussion on the potential of capsaicin and its analog, resiniferatoxin (RTX), for complete alleviation of nerve injury-induced neuropathic pain. In an animal model of neuropathic pain where the fifth lumbar (L5) spinal nerve is unilaterally ligated and cut, resulting in ipsilateral hyperalgesia, allodynia, and spontaneous pain akin to human neuropathic pain. The application of capsaicin or RTX to the adjacent uninjured L3 and L4 nerves completely alleviated and prevented mechanical and thermal hyperalgesia following the L5 nerve injury. The effects of this treatment were specific to unmyelinated fibers (responsible for pain sensation), while thick myelinated nerve fibers (responsible for touch and mechanoreceptor sensations) remained intact. Here, we propose to translate these promising preclinical results into effective therapeutic interventions in humans by direct application of capsaicin or RTX to adjacent uninjured nerves in patients who suffer from neuropathic pain due to peripheral nerve injury, following surgical interventions, diabetic neuropathy, trauma, vertebral disc herniation, nerve entrapment, ischemia, postherpetic lesion, and spinal cord injury. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury (PNI)-induced neuropathic pain (NP) is a severe disease with high prevalence in clinics. Gene reprogramming and tissue remodeling in the dorsal root ganglia (DRG) and spinal cord (SC) drive the development and maintenance of neuropathic pain (NP). However, our understanding of the NP-associated spatial molecular processing landscape of SC and the non-synaptic interactions between DRG neurons and SC cells remains limited. We here integrate spatial transcriptomics (ST) with single-nucleus RNA-sequencing (snRNA-seq) and bulk RNA-sequencing (bulk RNA-seq) to characterize regional pathological heterogeneity of the SC under NP conditions. First, the SC of NP mice manifests unique spatial atlases of genes, cell populations, cell-cell cross-talks, signaling pathways, and transcriptional regulatory networks compared to sham mice. We further report that injured DRG sensory neurons and the corresponding ventral horn of the SC show similar expression patterns after PNI. In addition, for the first time, we systematically exhibit "cross-talk omics" between the DRG neurons and SC dorsal horn neurons and glial cells, indicating an altered communication profile under NP conditions. Together, our findings decode the spatial and cellular heterogeneity of molecular pathological mechanisms underlying NP, providing a foundation for designing therapeutic targets for this disorder. Mechanistic modeling of enhancer-RNA sheds light on the role of transcription factors and their interactions in the context of estrogen- induced transcriptional program in breast cancer. Integrating snRNA-seq and spatial transcriptomics data reveals spatially altered profiles of genes, cell populations, intracellular molecular networks, cell-cell and cell-afferent cross-talks, in the spinal cord during neuropathic pain [ABSTRACT FROM AUTHOR]

Background: Carpal tunnel syndrome (CTS) is characterized as a compressive neuropathy of the median nerve and has several treatments, including photobiomodulation, which can be performed with low-intensity laser therapy (LLLT) and light-emitting diodes (LEDs). Purpose: To carry out a literature review on the effectiveness of low-intensity laser therapy (LLLT) in CTS. Methods: This study is characterized by being a systematic review with metaanalysis. The databases included were PubMed, Embase, Cochrane, the Physiotherapy Evidence Database (PEDro), Scopus and LILACS. Also, gray literature: Google Scholar, OpenGrey and CAPES Theses and Dissertations Catalog. The search was carried out in all databases on October 11, 2023 and updated on June 06, 2024. The risk of bias was assessed using the Cochrane tool, RoB 2, by two blinded reviewers and conflicts were resolved by consensus. The outcomes of interest were pain intensity (Visual analogue scale), strength (handgrip and pinch) and hand functionality (Boston questionnaire, Levine questionnaire, Purdue Pergboard Test). Statistical analysis was carried out using RevMan 5.4.1. Continuous results were expressed as standard mean differences (95% CI), with p-value of < 0.05 considered statistically significant. The value of the I2 statistical test was calculated to test for heterogeneity between studies. A random effects model was adopted. Results: 13 randomized controlled trials were selected from 1.613 records. In the general bias analysis, two studies (15,4%) were considered to have some relevant problems that could interfere with the quality of the study, and three (23,1%) were identified as having a high risk of bias, eight studies (61,5%) were classified as having a low risk of bias. In the meta-analysis, it was possible to observe that there were no advantages of the laser for pain (p = 0.08), nor for handgrip strength (p = 0.11), but it did produce improvements in functionality. Conclusion: It is concluded that LLLT is an effective therapeutic modality in the treatment of CTS, improving functionality; however, despite the studies pointing to advantages for the modality in reducing pain and improving grip strength, the meta-analysis did not show this result. Even so, there is a need for more clinical trials are needed to standardize dosimetry, mainly because the primary studies showed clinical advantages of PBM. Registration: Open Science Framework (OSF)—https://doi.org/10.17605/OSF.IO/HQCRP. [ABSTRACT FROM AUTHOR]

The document "Oxidative Stress and the Central Nervous System" published in the journal "Antioxidants" discusses the role of oxidative stress in neurodegenerative diseases and acute conditions affecting the central nervous system. It highlights the importance of antioxidant defenses in maintaining redox balance and the impact of environmental factors on neuronal dysfunction. The document includes original research articles and review papers exploring therapeutic approaches for oxidative-stress-related CNS diseases. The findings suggest potential interventions to mitigate oxidative stress and its detrimental effects on neurological conditions. [Extracted from the article]

Carpal Tunnel Syndrome (CTS) is a prevalent neuropathic disorder caused by chronic compression of the median nerve, leading to sensory and motor impairments. Conventional treatments, such as corticosteroid injections, wrist splinting, and surgical decompression, often fail to provide adequate outcomes for chronic or recurrent cases, emphasizing the need for innovative therapies. Hydrogels, highly biocompatible three-dimensional biomaterials with customizable properties, hold significant potential for CTS management. Their ability to mimic the extracellular matrix facilitates localized drug delivery, anti-adhesion barrier formation, and tissue regeneration. Advances in hydrogel engineering have introduced stimuli-responsive systems tailored to the biomechanical environment of the carpal tunnel, enabling sustained therapeutic release and improved tissue integration. Despite these promising developments, hydrogel applications for CTS remain underexplored. Key challenges include the absence of CTS-specific preclinical models and the need for rigorous clinical validation. Addressing these gaps could unlock the full potential of hydrogel-based interventions, which offer minimally invasive, customizable solutions that could improve long-term outcomes and reduce recurrence rates. This review highlights hydrogels as a transformative approach to CTS therapy, advocating for continued research to address translational barriers. These innovations have the potential to redefine the treatment landscape, significantly enhancing patient care and quality of life. [ABSTRACT FROM AUTHOR]

Objective(s): Peripheral nerve injury (PNI) is a critical clinical issue primarily caused by trauma. Tissue engineering approaches using nanofiber scaffolds have been extensively explored to improve material quality and create an environment resembling the natural extracellular matrix (ECM). Materials and Methods: In this study, we employed electrospinning technique to fabricate a composite scaffold comprising poly(ɛ-caprolactone) (PCL) and collagen (Col) loaded with all-trans retinoic acid (RA), a neural patterning and signaling chemical known to promote nerve regeneration. Results: The synthesized nanofiber scaffold exhibited a diameter of 391±79 nm and a tensile strength of 250±13 MPa, providing sufficient support for native peripheral nerve regeneration. The inclusion of Col enhanced the scaffold's hydrophilic behavior (contact angle: 43±6°), ensuring stability in an aqueous solution. Moreover, the results demonstrated the proliferation and adhesion of nerve cells on the scaffold, aligning with the directions of the warp and weft of the nanofiber mat. Importantly, the scaffolds demonstrated non-toxicity, making them a promising substitute for the native ECM for enhanced cell attachment and proliferation. Finally, immune-histochemistry analyses further confirmed that the scaffolds supported the release and growth of neurites, promoting cell differentiation toward nerve repair. Conclusion: The RA-loaded scaffolds demonstrated the enhanced biocompatibility, supported neurite growth, and showed potential as a capable candidate for nerve regeneration. [ABSTRACT FROM AUTHOR]

The peripheral nervous system (PNS) consists of nerves that extend beyond the brain and spinal cord, connecting the body to the central nervous system (CNS). Peripheral nerve injuries, caused by trauma, compression, or disease, often result in sensory and motor deficits. In the current study, a nanofibrous neural conduit was developed by loading Inula helenium extract into electrospun PCL/gelatin scaffolds. Then, the scaffolds were characterized in vitro using different analysis methods. Then, the electrospun sheets were rolled up to produce neural conduits. Finally, the healing efficacy of the developed system was investigated in a rat model of sciatic nerve injury. Results showed that the animals that were treated with both treadmill exercise and the Inula helenium extract-loaded conduits had significantly better functional recovery and histopathological recovery. ELISA assay showed that the hybrid treatment method increased tissue concentrations of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) and decreased tumor necrosis factor- α (TNF- α) tissue levels. [ABSTRACT FROM AUTHOR]

Background: Treatment of peripheral nerve defects is a major concern in regenerative medicine. This study therefore aimed to explore the efficacy of a neural graft constructed using adipose mesenchymal stem cells (ADSC), acellular microtissues (MTs), and chitosan in the treatment of peripheral nerve defects. Methods: Stem cell therapy with acellular MTs provided a suitable microenvironment for axonal regeneration, and compensated for the lack of repair cells in the neural ducts of male 8-week-old Sprague Dawley rats. Results: In vitro, acellular MTs retained the intrinsic extracellular matrix and improved the narrow microstructure of acellular nerves, thereby enhancing cell functionality. In vivo neuroelectrophysiological studies, gait analysis, and sciatic nerve histology demonstrated the regenerative effects of active acellular MT. The Chitosan + Acellular-MT + ADSC group exhibited superior myelin sheath quality and improved neurological and motor function recovery. Conclusions: Active acellular-MTs precellularized with ADSC hold promise as a safe and effective clinical treatment method for peripheral nerve defects. [ABSTRACT FROM AUTHOR]

Neuropathic pain (NP) is an ineffectively treated, debilitating chronic pain disorder that is associated with maladaptive changes in the central nervous system, particularly in the spinal cord. Murine models of NP looking at the mechanisms underlying these changes suggest an important role of microglia, the resident immune cells of the central nervous system, in various stages of disease progression. However, given the number of different NP models and the resource limitations that come with tracking longitudinal changes in NP animals, many studies fail to truly recapitulate the patterns that exist between pain conditions and temporal microglial changes. This review integrates how NP studies are being carried out in murine models and how microglia changes over time can affect pain behavior in order to inform better study design and highlight knowledge gaps in the field. 258 peer-reviewed, primary source articles looking at spinal microglia in murine models of NP were selected using Covidence. Trends in the type of mice, statistical tests, pain models, interventions, microglial markers and temporal pain behavior and microglia changes were recorded and analyzed. Studies were primarily conducted in inbred, young adult, male mice having peripheral nerve injury which highlights the lack of generalizability in the data currently being collected. Changes in microglia and pain behavior, which were both increased, were tested most commonly up to 2 weeks after pain initiation despite aberrant microglia activity also being recorded at later time points in NP conditions. Studies using treatments that decrease microglia show decreased pain behavior primarily at the 1- and 2-week time point with many studies not recording pain behavior despite the involvement of spinal microglia dysfunction in their development. These results show the need for not only studying spinal microglia dynamics in a variety of NP conditions at longer time points but also for better clinically relevant study design considerations. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury poses a significant challenge to the nervous system's regenerative capacity. We previously described a novel approach to construct a chitosan/silk fibroin nerve graft with skin-derived precursor-induced Schwann cells (SKP-SCs). This graft has been shown to promote sciatic nerve regeneration and functional restoration to a level comparable to that achieved by autologous nerve grafts, as evidenced by behavioral, histological, and electrophysiological assessments. However, the underlying molecular mechanisms based on SKP-SCs mediated tissue engineering-aid regeneration remain elusive. In the present work, we systematically identified gene modules associated with the differentiation of SKPs into SCs by employing weighted gene co-expression network analysis (WGCNA). By integrating transcriptomic data from the regenerated nerve segment, we constructed a network that delineated the molecular signatures of TENG aid neuroregeneration. Subsequent quantitative PCR (qPCR) validation was performed to substantiate the WGCNA findings. Our WGCNA approach revealed a robust molecular landscape, highlighting hub genes pivotal for tissue engineering-aid regeneration. Notably, the upregulation of specific genes was observed to coincide with the acquisition of SC characteristics. The qPCR validation confirmed the expression patterns of these genes, underscoring their role in promoting neuroregeneration. The current study harnesses the power of WGCNA to elucidate the molecular blueprint governing tissue engineering-aid regeneration. The identified gene modules and validated targets offer novel insights into the cellular and molecular underpinnings of tissue engineering-augmented neuroregeneration. These findings pave the way for developing targeted therapeutics and advanced tissue engineering grafts to enhance peripheral nerve repair. Highlights: A chitosan/silk fibroin nerve graft incorporating skin derived precursor-induced Schwann cells to enhance peripheral nerve regeneration. Used weighted correlation network analysis to identify hub gene modules and molecular signatures involved in peripheral nerve regeneration. Confirmed weighted correlation network analysis findings and common hub genes pivotal for tissue engineering-aid regeneration. [ABSTRACT FROM AUTHOR]

Traumatic peripheral nerve injuries (PNI) are debilitating and can leave patients severely limited with drastic changes in quality of life. PNI treatment options are varied; however, only 50% of those patients regain any useful function. The complex intrinsic organisation of nerves is largely contribute to this issue. This research aimed at creating a reliable way of isolating and predicting the location of peripheral nerve fascicles on microscopic images of nerve cross-sections via semantic segmentation and machine learning. Using the Anaconda Python platform, a machine learning algorithm was programmed using a random forest classifier. Training data resulted in a 91% accuracy rate with respect to correctly identifying image pixels as fascicle or not. When the trained model was tested in the real world with unseen data, the results varied. However, the model retained the ability to identify fascicles and isolate them from background. The development of clinically successful PNI treatments has long been hindered by intrinsic nerve structures that machine learning may be able to solve. With further development, this research has the potential to expand and form new frontiers in the field of clinical medicine and drastically improve outcomes of PNI. [ABSTRACT FROM AUTHOR]

In general, the nerve cells of the peripheral nervous system regenerate normally within a certain period after the physical damage of their axon. However, when peripheral nerves are transected by trauma or tissue extraction for cancer treatment, spontaneous nerve regeneration cannot occur. Therefore, it is necessary to perform microsurgery to connect the transected nerve directly or insert a nerve conduit to connect it. In this study, we applied human tonsillar mesenchymal stem cell (TMSC)-derived Schwann cell-like cells (TMSC-SCs) to facilitate nerve regeneration and prevent muscle atrophy after neurorrhaphy. The TMSC-SCs were manufactured in a good manufacturing practice facility and termed neuronal regeneration-promoting cells (NRPCs). A rat model of peripheral nerve injury (PNI) was generated and a mixture of NRPCs and fibrin glue was transplanted into the injured nerve after neurorrhaphy. The application of NRPCs and fibrin glue led to the efficient induction of sciatic nerve regeneration, with the sparing of gastrocnemius muscles and neuromuscular junctions. This sparing effect of NRPCs toward neuromuscular junctions might prevent muscle atrophy after neurorrhaphy. These results suggest that a mixture of NRPCs and fibrin glue may be a therapeutic candidate to enable peripheral nerve and muscle regeneration in the context of neurorrhaphy in patients with PNI. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal shock wave therapy (ESWT), as a non-invasive physical agent modality, was effective in relieving spasticity, reducing pain, and improving dysfunction. This systematic review and meta-analysis aimed to investigate the effect of ESWT on nerve conduction, and to find out whether the ESWT group is superior to the control or other comparison groups, thus providing support for guiding the rehabilitation of peripheral nerve injury in clinical work. Methods: PubMed, Web of Science, the Cochrane Library, and Embase were searched from inception to August 20, 2024. This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in the PROSPERO database (registration number CRD42024500891). It aimed to compare (1) the ESWT group (ESWT) and baseline, and (2) subgroup analyses: ESWT and the control group (Control), ESWT and the local corticosteroid injection group (LCI), ESWT combined with physical therapy (ESWT + PT) and PT alone, and ESWT and PT. Outcome indicators extracted were nerve conduction study results: sensory nerve action potential (SNAP) amplitude, SNAP distal latency, sensory nerve conduction velocity (SNCV), compound muscle action potential (CMAP) amplitude, motor nerve distal latency (MNDL), motor nerve conduction velocity (MNCV), H/M ratio and H-reflex latency. Results: A total of 879 papers were identified through the database searches. Twenty-four trials were included in the systematic review, and 22 trials were included in the meta-analysis. The results showed that: (1) compared to the baseline, ESWT reduced SNAP distal latency mid-term (MD, −0.39; 95% CI: −0.52, −0.26; I 2 = 85%), and improved SNCV both short-term (MD, 4.36; 95% CI: 1.23, 7.49; I 2 = 91%) and mid-term (MD, 2.65; 95% CI: 1.79, 3.51; I 2 = 61%). At the same time, it reduced MNDL short-term (MD, −0.61; 95% CI: −0.91, −0.30; I 2 = 92%), but had no significant effect on MNCV. (2) Subgroup analyses showed that ESWT was superior to Control but not significantly better than LCI, especially in SNCV. The excitatory effect of ESWT + PT on the sensory and motor nerves was significantly better than that of PT alone. Conclusion: ESWT had some excitatory effect on peripheral nerves, especially on sensory nerve studies. Although the efficacy of this treatment was superior to that of the control group, and the combined treatment with PT was more effective than PT alone, its efficacy might not exceed that of LCI. Systematic review registration: Unique identifier: PROSPERO (CRD42024500891). [ABSTRACT FROM AUTHOR]

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+F4/80hi tissue-resident (TRM) and CD11b+F4/80int 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. [ABSTRACT FROM AUTHOR]

Copyright of Rehabilitation / Rehabilitacija is the property of University Rehabilitation Institute, Republic of Slovenia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Peripheral nerve injury has become an increasingly prevalent clinical concern, causing great morbidity in the community. Although there have been significant advancements in the treatment of peripheral nerve damage in recent years, the issue of long-term nerve regeneration remains. Furthermore, Wallerian degeneration has created an obstacle to long-term nerve regeneration. For this reason, there has been extensive research on the use of exogenous and endogenous stem cells as an adjunct or even primary treatment option for peripheral nerve injury. The plasticity and inducibility of stem cells make them an enticing option for initiating neuronal cell regrowth and optimal sensory and functional nerve regeneration. Peripheral nerve injury has a broad range of causative factors and etiologies. As such, unique stem cell-induced peripheral nerve treatments are being investigated to ameliorate the damage incited by all causes, including trauma, neuropathy, and systemic neurodegenerative diseases. This review is oriented to outline the potential role of stem cell therapies in peripheral nerve injury versus the current standards of care, compare the benefits and drawbacks of specific stem cell lines under investigation, and highlight the current models of stem cell therapy in the peripheral nervous system, with the ultimate goal of narrowing down and optimizing the role and scope of stem cell therapy in peripheral nerve injury. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background/Objectives: Photobiomodulation therapy (PBM) creates a biostimulatory or modulatory effect, promoting tissue regeneration and improving patients' health-related quality of life (HRQoL). PBM has shown promise as an effective treatment and management strategy for peripheral nerve injuries, including inferior alveolar nerve (IAN) damage. This study aims to assess the impact of PBM on HRQoL in patients with iatrogenic IAN injuries. Methods: A prospective study was implemented to investigate the research question. PBM treatments were administered weekly, with patient discharge contingent upon either complete recovery or stabilization of associated signs and symptoms. HRQoL was assessed using the EQ-5D-5L questionnaire at the initial and final appointments. Results: The study included 71 participants, divided into 3 groups based on etiology: inferior third molar surgery, mandibular orthognathic surgery, and dental implant surgery. The results showed a widespread reduction of symptoms along with a statistically significant improvement (p < 0.001) across four of the five dimensions of the EQ-5D-5L questionnaire, as well as in patients' perceived health levels in both Groups I and II. Group III patients also demonstrated a notable improvement; however, due to the small sample size, statistical analysis was not conducted for this group. Conclusions: PBM demonstrated a comparable ability to enhance HRQoL and alleviate symptoms in patients with IAN injuries within different etiologies. These findings underscore the effectiveness of the protocol used in this study and highlight potential avenues for expanding research in this field. [ABSTRACT FROM AUTHOR]

Background: Peripheral nerve injury is a challenging orthopedic issue in clinical management that often leads to limb dysfunction or even disability in severe cases. A thorough exploration of the repair process of peripheral nerve injury and the underlying mechanism contributes to formulate more effective therapeutic strategies. Methods: In the present study, we established a sciatic nerve transection injury model in Sprague-Dawley (SD) rats. A 12-week compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis was then performed via sleeve jointing the proximal common peroneal nerve to the distal tibial nerve and common peroneal nerve, with a 2 mm interval. Compensatory repair via small gap amplification was observed via gross observation of nerve specimen, osmic acid staining, and electrophysiological stimulation of sciatic nerve branches of the tibial and common peroneal nerve. Rat limbs were observed, and the functional recovery of effector muscles of the gastrocnemius and tibialis anterior muscles was assessed through weighing the muscle wet weight, Hematoxylin and Eosin (H&E) staining, and muscle strength detection. H&E staining, Masson staining, and toluidine blue staining were performed to observe the morphological changes of the dorsal root ganglion. Positive expressions of key proteins involved in the Phosphatase and tensin homologue deleted on chromosome ten (PTEN)-protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, including PTEN, AKT, mTOR, Toll-like receptor 4 (TLR4), and Caspase9 in the dorsal root ganglion during compensatory repair of sciatic nerve after injury via small gap amplification, were detected by immunohistochemical staining. Results: It is found that the compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis via sleeve jointing effectively restored the continuity, number of myelinated nerve fibers, and nerve conduction velocity. It promoted toe abduction recovery, improved muscle fiber morphology and increased the wet weight and muscle strength of the gastrocnemius muscle and tibialis anterior muscle. Moreover, it increased the number of neurons and nerve fibers, and improved their morphology. Downregulated PTEN, TLR4, and Caspase9 in the dorsal root ganglia and upregulated AKT and mTOR were observed after small gap amplification than those of the transection injury group, which were closer to those of the control group. Conclusions: Compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis via sleeve jointing can restore the morphology and function of the sciatic nerve, effector muscles, and corresponding dorsal root ganglia by activating the PTEN-AKT/mTOR signaling pathway in the dorsal root ganglia. Our findings provide novel therapeutic targets for peripheral nerve injuries. [ABSTRACT FROM AUTHOR]

ATP synthase inhibitory factor 1 (ATPIF1), a key modulator of ATP synthase complex activity, has been implicated in various physiological and pathological processes. While its role is established in conditions such as hypoxia, ischemia‐reperfusion injury, apoptosis, and cancer, its involvement remains elusive in peripheral nerve regeneration. Leveraging ATPIF1 knockout transgenic mice, this study reveals that the absence of ATPIF1 impedes neural structural reconstruction, leading to delayed sensory and functional recovery. RNA‐sequencing unveils a significant attenuation in immune responses following peripheral nerve injury, which attributes to the CCR2/CCL2 signaling axis and results in decreased macrophage infiltration and activation. Importantly, macrophages, not Schwann cells, are identified as key contributors to the delayed Wallerian degeneration in ATPIF1 knockout mice, and affect the overall outcome of peripheral nerve regeneration. These results shed light on the translational potential of ATPIF1 for improving peripheral nerve regeneration. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Tissue Engineering Research / Zhongguo Zuzhi Gongcheng Yanjiu is the property of Chinese Journal of Tissue Engineering Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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With the rapid progress of industrialization, the incidence of peripheral nerve injuries caused by trauma has been continuously increasing. These injuries result in a significant number of disabilities and irreversible functional impairments, not only severely impacting the health and quality of life of patients but also placing a heavy economic burden on families and society. Effectively promoting peripheral nerve regeneration has thus become a key focus and challenge in current research. In recent years, hybrid biohydrogels with adhesive properties have gained widespread attention due to their excellent biocompatibility, mechanical stability, conductivity, and biodegradability. These materials can provide an optimal microenvironment to promote neuron adhesion and axonal extension while offering outstanding mechanical strength to meet the fixation requirements in clinical surgeries. This paper systematically reviews the application of adhesive hybrid biohydrogels in peripheral nerve injury repair, highlighting the latest research progress in promoting nerve regeneration and improving functional recovery, and discusses the challenges and future prospects for their clinical application. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury may result in muscle atrophy and impaired motor function recovery, and numerous pieces of evidence indicate that long noncoding RNAs (lncRNAs) play crucial roles in skeletal muscle regeneration. Our preliminary sequencing results showed that LNC_000280 was significantly down-regulated in denervated mouse skeletal muscle and we hypothesized that LNC_000280 may play an important role in skeletal muscle regeneration. In this research, flow cytometry and EdU staining results showed that overexpression of LNC_000280 promoted the proliferation of C2C12, while knockdown LNC_000280 had the opposite effect. Knockdown LNC_000280 inhibited the differentiation of C2C12 cells. LNC_000280 regulated the expression of proliferation genes (Cdk2, Cdc27) and differentiation genes (MyoG, MyoD). GO analysis and PPI network of LNC_000280 target genes showed that LNC_000280 mainly regulates skeletal muscle cell metabolism, mitochondrial and muscle growth. Idh2, Klhl31, Agt, and Gpt2 may be important downstream targets for its function. Therefore, we believe that that LNC_000280 can regulate the proliferation and differentiation of myoblasts by regulating gene expression. [ABSTRACT FROM AUTHOR]

Improved treatment options are urgently needed for neurological injuries resulting from trauma or iatrogenic events causing long-term disabilities that severely impact patients' quality of life. In vitro and animal studies have provided promising proof-of-concept examples of regenerative therapies using mesenchymal stromal cells (MSC) for a wide range of pathological conditions. Over the previous decade, various MSC-based therapies have been investigated in clinical trials to treat traumatic neurological injuries. However, while the safety and feasibility of MSC treatments has been established, the patient outcomes in these studies have not demonstrated significant success in the translation of MSC regenerative therapy for the treatment of human brain and spinal cord injuries. Herein, we have reviewed the literature and ongoing registered trials on the application of MSC for the treatment of traumatic brain injury, traumatic spinal cord injury, and peripheral nerve injury. We have focused on the shortcomings and technological hurdles that must be overcome to further advance clinical research to phase 3 trials, and we discuss recent advancements that represent potential solutions to these obstacles to progress. [ABSTRACT FROM AUTHOR]

Background: Peripheral nerve injuries (PNIs) are associated with significant physical and psychological challenges, impacting both functional recovery and quality of life. Despite the physical focus of traditional treatments, psychological factors play a crucial role in the outcomes of PNI repair and recovery. Objectives: This systematic review aims to evaluate the impact of psychological and social factors on the repair and recovery of peripheral nerve injuries. Methods: A comprehensive literature search was conducted in PubMed/Medline, EMBASE, and Cochrane databases, covering studies from January 1985 to December 2022. A total of 36,190 records were identified, and after screening with Rayyan AI and applying inclusion criteria, 111 articles were selected for review. Results: The review highlights that pre-existing psychological conditions, as well as psychological responses to the injury and treatment, significantly influence recovery outcomes in PNI patients. Psychological interventions, when integrated into standard care, may improve functional recovery and quality of life. Conclusions: Psychosocial factors are critical in the management of PNIs and should be incorporated into treatment algorithms to enhance patient outcomes. Future research should focus on developing and integrating psychological support strategies in PNI treatment protocols. [ABSTRACT FROM AUTHOR]

Background: Peripheral nerve injuries (PNIs) are associated with significant physical and psychological challenges, impacting both functional recovery and quality of life. Despite the physical focus of traditional treatments, psychological factors play a crucial role in the outcomes of PNI repair and recovery. Objectives: This systematic review aims to evaluate the impact of psychological and social factors on the repair and recovery of peripheral nerve injuries. Methods: A comprehensive literature search was conducted in PubMed/Medline, EMBASE, and Cochrane databases, covering studies from January 1985 to December 2022. A total of 36,190 records were identified, and after screening with Rayyan AI and applying inclusion criteria, 111 articles were selected for review. Results: The review highlights that pre-existing psychological conditions, as well as psychological responses to the injury and treatment, significantly influence recovery outcomes in PNI patients. Psychological interventions, when integrated into standard care, may improve functional recovery and quality of life. Conclusions: Psychosocial factors are critical in the management of PNIs and should be incorporated into treatment algorithms to enhance patient outcomes. Future research should focus on developing and integrating psychological support strategies in PNI treatment protocols. [ABSTRACT FROM AUTHOR]

The synaptic connections between dorsal root ganglia (DRG) and dorsal horn (DH) neurons are a crucial relay point for the transmission of painful stimuli. To delineate how synaptic plasticity may modulate the excitability of DH neurons, we have devised a microfluidic co-culture model that recapitulates the first sensory synapse using postnatal mouse sensory neurons. We show that DRG-DH co-cultures characterize salient features of the in vivo physiology of sensory neurons. Immunocytcochemical experiments of the cultured DH neurons show a co-localization of Map2 with VGlut2 and of Map2 with Synapsin 1, corroborating the glutamatergic identity of the DH neurons and further suggesting the potential formation of active synapses in this neuronal set. Fluorometric imaging experiments demonstrate the elicitation of calcium responses in DH neurons following the stimulation of DRG cell bodies or axons. Selective NMDA and AMPA receptor blockade appreciably silences DH neuron responses, suggesting that glutamatergic signaling is maintained in vitro. Last, a surrogate model of peripheral nerve injury is introduced in the form of an axotomy, which results in elevated and prolonged calcium responses of DH neurons. Overall, the microfluidic mouse co-cultures provide a method advancement in the study of periphery-to-center pain signaling, where the potential of utilizing the platform for drug target identification is underscored. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Facial nerve baroparesis is a peripheral facial nerve injury resulting from barotrauma during activities such as diving, aviation, and mountain climbing. This condition occurs when increased pressure in the middle ear affects the facial nerve, leading to facial palsy. Despite being documented in otolaryngology literature, facial nerve baroparesis remains underreported and often misunderstood. Enhanced awareness and education about this condition are essential for effectively managing affected patients, helping to mitigate unnecessary panic and procedures during episodes. Case presentation: We present two cases of facial nerve baroparesis that occurred during flights. The first case involves a 25-year-old Arab male with no significant medical history who experienced a transient, one-time episode of right-sided facial nerve baroparesis during a flight from Kuwait to Syria; he reported nasal congestion and a sore throat prior to the flight, with the episode lasting approximately 30 min before resolving spontaneously. The second case is a 30-year-old Arab female with a history of chronic allergic rhinitis, who has experienced recurrent episodes of left-sided facial nerve baroparesis for the past 2 years, occurring during nearly every flight; each episode lasted around 5 min, caused severe facial pain, and also resolved spontaneously. Both patients exhibited varying degrees of Eustachian tube dysfunction. Treatment for the recurrent case included maneuvers to alleviate ear pressure and the use of nasal decongestants, which improved symptoms and decreased the frequency of episodes. Conclusion: Facial nerve baroparesis is frequently underestimated due to its temporary nature, yet it remains a significant cause of facial nerve palsy, especially after changes in pressure. Although the underlying mechanisms are not completely understood, dysfunction of the Eustachian tube is believed to be a contributing factor. Identifying the characteristic features of baroparesis—such as rapid onset, brief duration, and bilateral involvement of facial muscles—is essential for effective management. This highlights the necessity of educating healthcare professionals and flight personnel about this condition to prevent unnecessary treatments. For recurrent cases, management strategies should focus on alleviating Eustachian tube dysfunction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The transcription repressor REST in the dorsal root ganglion (DRG) is upregulated by peripheral nerve injury and promotes the development of chronic pain. However, the genes targeted by REST in neuropathic pain development remain unclear. The expression levels of four opioid receptor genes (Oprm1, Oprd1, Oprl1 and Oprk1) and the cannabinoid CB1 receptor (Cnr1) gene in the DRG regulate nociception. In this study, we determined the role of REST in controlling their expression in the DRG induced by spared nerve injury (SNI). SNI induced chronic pain hypersensitivity in wild-type mice and was accompanied by increased levels of Rest transcript and protein. Transcriptomic analyses of wild-type mouse DRGs suggested that SNI upregulates the expression of Rest transcripts and downregulates the transcripts of all four opioid receptor genes and the Cnr1 gene. Quantitative reverse transcription polymerase chain reaction analyses of these tissues validated these results. Analysis of publicly available bioinformatic data suggested that REST binds to the promoter regions of Oprm1 and Cnr1. Chromatin immunoprecipitation analyses indicated the presence of REST at these promoters. Full-length Rest conditional knockout in primary sensory neurons reduced SNI-induced pain hypersensitivity and rescued the SNI-induced reduction in the expression of Oprd1 and Cnr1 in mouse DRG. Our results suggest that nerve injury represses the transcription of at least the Oprd1 and Cnr1 genes via REST in primary sensory neurons and that REST is a potential therapeutic target for neuropathic pain. Thus, inhibiting REST activity could potentially reduce chronic neuropathic pain and augment opioid/cannabinoid analgesic actions by increasing the transcription of Oprd1 and Cnr1 genes in DRG neurons. [ABSTRACT FROM AUTHOR]

Injury to the peripheral nervous system disconnects targets to the central nervous system, disrupts signal transmission, and results in functional disability. Although surgical and therapeutic treatments improve nerve regeneration, it is generally hard to achieve fully functional recovery after severe peripheral nerve injury. A better understanding of pathological changes after peripheral nerve injury helps the development of promising treatments for nerve regeneration. Single-cell analyses of the peripheral nervous system under physiological and injury conditions define the diversity of cells in peripheral nerves and reveal cell-specific injury responses. Herein, we review recent findings on the single-cell transcriptome status in the dorsal root ganglia and peripheral nerves following peripheral nerve injury, identify the cell heterogeneity of peripheral nerves, and delineate changes in injured peripheral nerves, especially molecular changes in neurons, glial cells, and immune cells. Cell-cell interactions in peripheral nerves are also characterized based on ligand-receptor pairs from coordinated gene expressions. The understanding of cellular changes following peripheral nerve injury at a single-cell resolution offers a comprehensive and insightful view for the peripheral nerve repair process, provides an important basis for the exploration of the key regulators of neuronal growth and microenvironment reconstruction, and benefits the development of novel therapeutic drugs for the treatment of peripheral nerve injury. [ABSTRACT FROM AUTHOR]

Introduction: Ferroptosis is a new type of cell death characterized by lipid peroxidation and iron dependency, representing an emerging disease regulation mechanism. The limited understanding of ferroptosis in peripheral nerve injury (PNI) complicates the management of such injuries. Mitochondrial dysfunction, which contributes to ferroptosis, further exacerbates the challenges of peripheral nerve repair Methods: In this study, we established an in vitro model of Schwann cells model treated with TBHP and an in vivo sciatic nerve crush injury model in rats. These models were used to investigate the effects of fibroblast growth factor 21 (FGF21) on PNI, both in vitro and in vivo, and to explore the potential mechanisms linking injury-induced ferroptosis and mitochondrial dysfunction. Results: Our findings reveal that PNI triggers abnormal accumulation of lipid reactive oxygen species (ROS) and inactivates mitochondrial respiratory chain complex III, leading to mitochondrial dysfunction. This dysfunction catalyzes the oxidation of excessive polyunsaturated fatty acids, resulting in antioxidant imbalance and loss of ferroptosis suppressor protein 1 (FSP1), which drives lipid peroxidation. Additionally, irregular iron metabolism, defective mitophagy, and other factors contribute to the induction of ferroptosis. Importantly, we found that FGF21 attenuates the abnormal accumulation of lipid ROS, restores mitochondrial function, and suppresses ferroptosis, thus promoting PNI repair. Notably, glutathione peroxidase 4 (GPX4), a downstream target of nuclear factor E2-related factor 2 (Nrf2), and the ERK/Nrf2 pathway are involved in the regulation of ferroptosis by FGF21. Conclusion: FGF21 promotes peripheral nerve repair by inhibiting ferroptosis caused by mitochondrial dysfunction. Therefore, targeting mitochondria and ferroptosis represents a promising therapeutic strategy for effective PNI repair. [ABSTRACT FROM AUTHOR]

Background We explore a minimally invasive method (combined ultrasound detection, electrode placement and electrophysiologic nerve examination) to evaluate the early-stage quality of a nerve suture site. Methods Ten patients with median and/or ulnar nerve injuries who had undergone nerve suture were recruited. Postoperative ultrasound examination found that the nerve injury was sutured. Then, a stimulating electrode and recording electrode were located beside the nerve proximal and distal to the suture site guided by ultrasound. Measurement of nerve action potentials (NAP) were performed with these electrodes, followed by surgical exploration. The pre- and intraoperative electrophysiologic findings were compared, together with amplitude, latency, and wave shape of NAP. Results Of the 10 patients, 3 patients were diagnosed with median nerve injury, 2 with ulnar nerve injury, and 5 with the median nerve and ulnar nerve injury. NAP could not be detected pre- and intraoperatively in three median nerves from three patients and in two ulnar nerves from two patients. NAP was detected in 10 nerves from the remaining 5 patients. The pre- and intraoperative NAP results showed consistent results concerning the status of the nerve suture. Wilcoxon's signed-rank test indicated no significant difference in the amplitude and latency detected via sonographically placed electrodes and during surgical exploration. The number of negative-phase waves were equally distributed. Conclusion Ultrasound-guided electrode placement and NAP detection can substitute surgery and serve as a minimally invasive approach to evaluate the regeneration of a sutured nerve. [ABSTRACT FROM AUTHOR]

Background: Muscle atrophy caused by denervation is common in neuromuscular diseases, leading to loss of muscle mass and function. However, a comprehensive understanding of the overall molecular network changes during muscle denervation atrophy is still deficient, hindering the development of effective treatments. Method: In this study, a sciatic nerve transection model was employed in male C57BL/6 J mice to induce muscle denervation atrophy. Gastrocnemius muscles were harvested at 3 days, 2 weeks, and 4 weeks post-denervation for transcriptomic and proteomic analysis. An integrative multi-omics approach was utilized to identify key genes essential for disease progression. Targeted proteomics using PRM was then employed to validate the differential expression of central genes. Combine single-nucleus sequencing results to observe the expression levels of PRM-validated genes in different cell types within muscle tissue.Through upstream regulatory analysis, NRF2 was identified as a potential therapeutic target. The therapeutic potential of the NRF2-targeting drug Omaveloxolone was evaluated in the mouse model. Result: This research examined the temporal alterations in transcripts and proteins during muscle atrophy subsequent to denervation. A comprehensive analysis identified 54,534 transcripts and 3,218 proteins, of which 23,282 transcripts and 1,852 proteins exhibited statistically significant changes at 3 days, 2 weeks, and 4 weeks post-denervation. Utilizing multi-omics approaches, 30 hubgenes were selected, and PRM validation confirmed significant expression variances in 23 genes. The findings highlighted the involvement of mitochondrial dysfunction, oxidative stress, and metabolic disturbances in the pathogenesis of muscle atrophy, with a pronounced impact on type II muscle fibers, particularly type IIb fibers. The potential therapeutic benefits of Omaveloxolone in mitigating oxidative stress and preserving mitochondrial morphology were confirmed, thereby presenting novel strategies for addressing muscle atrophy induced by denervation. GSEA analysis results show that Autophagy, glutathione metabolism, and PPAR signaling pathways are significantly upregulated, while inflammation-related and neurodegenerative disease-related pathways are significantly inhibited in the Omaveloxolone group.GSR expression and the GSH/GSSG ratio were significantly higher in the Omaveloxolone group compared to the control group, while MuSK expression was significantly lower than in the control group. Conclusion: In our study, we revealed the crucial role of oxidative stress, glucose metabolism, and mitochondrial dysfunction in denervation-induced muscle atrophy, identifying NRF2 as a potential therapeutic target. Omaveloxolone was shown to stabilize mitochondrial function, enhance antioxidant capacity, and protect neuromuscular junctions, thereby offering promising therapeutic potential for treating denervation-induced muscle atrophy. [ABSTRACT FROM AUTHOR]

Background: Muscle atrophy caused by denervation is common in neuromuscular diseases, leading to loss of muscle mass and function. However, a comprehensive understanding of the overall molecular network changes during muscle denervation atrophy is still deficient, hindering the development of effective treatments. Method: In this study, a sciatic nerve transection model was employed in male C57BL/6 J mice to induce muscle denervation atrophy. Gastrocnemius muscles were harvested at 3 days, 2 weeks, and 4 weeks post-denervation for transcriptomic and proteomic analysis. An integrative multi-omics approach was utilized to identify key genes essential for disease progression. Targeted proteomics using PRM was then employed to validate the differential expression of central genes. Combine single-nucleus sequencing results to observe the expression levels of PRM-validated genes in different cell types within muscle tissue.Through upstream regulatory analysis, NRF2 was identified as a potential therapeutic target. The therapeutic potential of the NRF2-targeting drug Omaveloxolone was evaluated in the mouse model. Result: This research examined the temporal alterations in transcripts and proteins during muscle atrophy subsequent to denervation. A comprehensive analysis identified 54,534 transcripts and 3,218 proteins, of which 23,282 transcripts and 1,852 proteins exhibited statistically significant changes at 3 days, 2 weeks, and 4 weeks post-denervation. Utilizing multi-omics approaches, 30 hubgenes were selected, and PRM validation confirmed significant expression variances in 23 genes. The findings highlighted the involvement of mitochondrial dysfunction, oxidative stress, and metabolic disturbances in the pathogenesis of muscle atrophy, with a pronounced impact on type II muscle fibers, particularly type IIb fibers. The potential therapeutic benefits of Omaveloxolone in mitigating oxidative stress and preserving mitochondrial morphology were confirmed, thereby presenting novel strategies for addressing muscle atrophy induced by denervation. GSEA analysis results show that Autophagy, glutathione metabolism, and PPAR signaling pathways are significantly upregulated, while inflammation-related and neurodegenerative disease-related pathways are significantly inhibited in the Omaveloxolone group.GSR expression and the GSH/GSSG ratio were significantly higher in the Omaveloxolone group compared to the control group, while MuSK expression was significantly lower than in the control group. Conclusion: In our study, we revealed the crucial role of oxidative stress, glucose metabolism, and mitochondrial dysfunction in denervation-induced muscle atrophy, identifying NRF2 as a potential therapeutic target. Omaveloxolone was shown to stabilize mitochondrial function, enhance antioxidant capacity, and protect neuromuscular junctions, thereby offering promising therapeutic potential for treating denervation-induced muscle atrophy. [ABSTRACT FROM AUTHOR]

Background: Schwann cells (SCs) and their plasticity contribute to the peripheral nervous system's capacity for nerve regeneration after injury. The Egr2/Krox20 promoter antisense RNA (Egr2-AS) recruits chromatin remodeling complexes to inhibit Egr2 transcription following peripheral nerve injury. Methods: RNA-seq and ATAC-seq were performed on control cells, Lenti-GFP-transduced cells, and cells overexpressing Egr2-AS (Lenti-AS). Egr2 AS-RNA was cloned into the pLVX-DsRed-Express2-N1 lentiviral expression vector (Clontech, Mountain View, CA, USA), and the levels of AS-RNA expression were determined. Ezh2 and Wdr5 were immunoprecipitated from rat SCs and RT-qPCR was performed against AS-Egr2 RNA. ChIP followed by DNA purification columns was used to perform qPCR for relevant promoters. Hi-C, HiC-DC+, R, Bioconductor, and TOBIAS were used for significant and differential loop analysis, identifications of COREs and CORE-promotor loops, comparisons of TF activity at promoter sites, and identification of site-specific TF footprints. OnTAD was used to detect TADs, and Juicer was used to identify A/B compartments. Results: Here we show that a Neuregulin-ErbB2/3 signaling axis mediates binding of the Egr2-AS to YY1Ser184 and regulates its expression. Egr2-AS modulates the chromatin accessibility of Schwann cells and interacts with two distinct histone modification complexes. It binds to EZH2 and WDR5 and enables targeting of H3K27me3 and H3K4me3 to promoters of Egr2 and C-JUN, respectively. Expression of the Egr2-AS results in reorganization of the global chromatin landscape and quantitative changes in the loop formation and contact frequency at domain boundaries exhibiting enrichment for AP-1 genes. In addition, the Egr2-AS induces changes in the hierarchical TADs and increases transcription factor binding scores on an inter-TAD loop between a super-enhancer regulatory hub and the promoter of mTOR. Conclusions: Our results show that Neuregulin-ErbB2/3-YY1 regulates the expression of Egr2-AS, which mediates remodeling of the chromatin landscape in Schwann cells. [ABSTRACT FROM AUTHOR]

Peripheral nerve injuries (PNIs) resulting in myelin breakdown and axonal degeneration at both the proximal and distal nerve stumps are major clinical concerns that can induce functional loss and diminished quality of life. In biomaterials science, considerable attention has been given to artificial nerve guidance conduits (NGCs), since the engineered tubular structures have the potential to supply a supportive nerve microenvironment to longitudinally align the regenerating axons for bridging the injured nerve sites. Although NGCs may become promising alternatives to nerve autografts, the fabrication approaches available to incorporate directional cues for dictating neuronal behavior and nerve reconnection have been limited to conventional micro/nano‐fabrication techniques that are complex and time‐consuming due to manual processing steps. Thus, our goal here was to develop a simple manufacturing approach for introducing topographical cues onto NGCs. To achieve this goal, we used an established mechanically actuated silk wrinkling approach to create topographically functionalized surfaces as a potential NGC material platform for guided directional alignment of neurons. We 3D‐printed thermo‐responsive shape‐memory polymer (SMP)‐based NGCs that can produce silk fibroin (SF)‐wrinkled topographies on the micro and nano‐meter length scale. Since SF is a commonly used biomaterial surface coating with excellent neuro‐compatibility, we studied the ability to develop NGCs that can autonomously actuate silk wrinkles upon heat‐induced contraction of the SMP and evaluated the effects of the topographically functionalized construct on neuronal behavior. Using an immortalized dorsal root ganglion neuronal cell line, we found that the silk‐wrinkled conduits displayed high neuronal viability and adhesion compared to uncoated conduits and tissue‐culture polystyrene controls. We also found that the wrinkled conduits enabled the neurons to elongate and align parallel to the direction of the wrinkled topography. Longer neurite extension was also observed on the wrinkled conduits compared to their respective controls. These findings demonstrate the potential for functional wrinkled protein coatings to provide directional cues in the fabrication of artificial NGCs for peripheral nerve repair. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to determine the incidence, necessity for neurosurgical intervention, and overall results of the treatment of pediatric peripheral nerve injuries associated with dislocated supracondylar fractures of the distal humerus. Method: A retrospective analysis of pediatric patients with supracondylar fractures treated from April 2019 to April 2022 with a minimum follow-up of 3 months was conducted. Results: Of 453 included patients, there were 51 recorded peripheral nerve injuries. The ulnar nerve was the most frequently injured nerve. Nine patients required neurosurgical intervention, with the most common procedure being the release of entrapped nerves. The combination of a supracondylar fracture and arterial injury was identified as a significant risk factor for peripheral nerve injury (p < 0.001). Only one patient experienced an unsatisfactory outcome. Conclusion: Although the prognosis for peripheral nerve injuries in children with supracondylar fractures is generally favorable, these injuries must be properly identified. We recommend an active neurosurgical approach in children with persisting neurological deficits to minimize the risk of permanent neurological impairment. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury (PNI) often leads to significant functional impairment. Here, we investigated the impact of epidermal growth factor‐like domain‐containing protein 7 (EGFL7) on angiogenesis and nerve regeneration following PNI. Using a sciatic nerve injury model, we assessed nerve function using the sciatic nerve function index. We analyzed the expression levels of EGFL7, forkhead box proteins A1 (FOXA1), nerve growth factor (NGF), brain‐derived neurotrophic factors (BDNF), Neurofilament 200 (NF200), myelin protein zero (P0), cell adhesion molecule 1 (CD31), vascular endothelial growth factor (VEGF), and NOTCH‐related proteins in tissues and cells. Cell proliferation, migration, and angiogenesis were evaluated through cell counting kit assays, 5‐ethynyl‐2′deoxyuridine staining, and Transwell assays. We investigated the binding of FOXA1 to the EGFL7 promoter using dual‐luciferase assays and chromatin immunoprecipitation. We observed decreased EGFL7 expression and increased FOXA1 expression in PNI, and EGFL7 overexpression alleviated gastrocnemius muscle atrophy, increased muscle weight, and improved motor function. Additionally, EGFL7 overexpression enhanced Schwann cell and endothelial cell proliferation and migration, promoted tube formation, and upregulated NGF, BDNF, NF200, P0, CD31, and VEGF expression. FOXA1 was found to bind to the EGFL7 promoter region, inhibiting EGFL7 expression and activating the NOTCH signaling pathway. Notably, FOXA1 overexpression counteracted the effects of EGFL7 on Schwann cells and endothelial cells. In conclusion, EGFL7 holds promise as a therapeutic molecule for treating sciatic nerve injury. [ABSTRACT FROM AUTHOR]

Elbow injuries are common in judo, particularly among adolescents. This study investigated the incidence and patterns of three types of elbow injuries (sprain, dislocation, and fracture-dislocation) among Japanese adolescent judo players (12 to 18 years old) using data from a nationwide insurance database, covering the period from 2010 to 2019. A total of 4614 elbow injuries were recorded, with sprains being the most frequent (67.6% of cases). Female players had a 20% higher incidence of sprains than male players (6.8 vs. 5.4 per 1000 athlete-years). Severe injuries, such as dislocations and fracture-dislocations, were more common in high school players, with male middle school students exhibiting a higher rate of elbow fracture-dislocations (+15%) compared with female students. Elbow injuries frequently occurred during te-waza techniques, particularly seoi-nage, when players extended their arms to prevent being thrown. Peripheral nerve injuries, predominantly ulnar nerve injuries, accompanied elbow dislocations in 74% of the cases. This study highlights the importance of proper instruction in defensive and ukemi techniques, particularly those that discourage the use of hands to prevent falls during throws, to reduce the risk of elbow injuries. [ABSTRACT FROM AUTHOR]

Peripheral nerve damage can cause debilitating symptoms ranging from numbness and pain to sensory loss and atrophy. To uncover the underlying mechanisms of peripheral nerve injury, our research aims to develop a relationship between biomechanical peripheral nerve damage and function through finite element modeling. A noncontact, ex vivo electrophysiology chamber, capable of axially stretching explanted nerves while recording electrical signals, was used to investigate peripheral nerve injury. Successive stretch trials were run on eight sciatic nerves (four females and four males) excised from Sprague–Dawley rats. Nerves were stretched until 50% compound action potential (CAP) amplitude reduction was obtained. A constitutive model developed by Raghavan and Vorp was suitable for rat sciatic nerves, with an average α and β of 0.183 MPa and 1.88 MPa, respectively. We then generated 95% confidence intervals for the stretch at which specific CAP amplitude reductions would occur, which compares well to previous studies. We also developed a finite element model that can predict stretch‐induced signaling deficits, applicable for complex nerve geometries and injuries. This relationship between nerve biomechanics and function can be expanded upon to create a clinical model for peripheral nerve dysfunction due to stretch. [ABSTRACT FROM AUTHOR]

Low‐intensity pulsed ultrasound (LIPUS) and electrical stimulation (ES) are effective methods that promote neural repair. However, ES usually requires electrode implantation and a power supply, which are an inconvenience to future applications. Meanwhile, it is difficult to combine ultrasound and ES through traditional methods. Herein, a nanopatch consisting of an oriented barium titanate (BTO)‐incorporated polycaprolactone (PCL) nanofiber membrane for electricity generation and a layer of graphene oxide (GO)‐doped gelatin methacryloyl (GelMA) for neural interaction is developed. This band‐aid‐like BTO@PCL/GO@GelMA nanopatch has an excellent piezoelectric performance. In vitro, the nanopatches significantly promote axonal growth under LIPUS treatment. In a rat model of erectile dysfunction caused by peripheral nerve injury, the nanopatch is easily attached to a damaged nerve similar to a band‐aid. With the assistance of ultrasound, some mechanical energy is converted into electricity by the nanopatch, and synergistic neural stimulation of ultrasound and electricity is achieved. In this way, the nanopatch significantly promoted corpus cavernosum nerve repair, resulting in the improvement of tissue structure and erectile function as well as increased conception rate in female rats. In conclusion, the nanopatch offers a synergistic ultrasound‐ES for nerve repair easily and represents a novel strategy for peripheral nerve repair. [ABSTRACT FROM AUTHOR]

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. Peripheral nerves slowly regrow after injury, but often fail to form functional synapses. Here, authors use NANOG, a pluripotency factor, to induce denervated muscle to a pro-regenerative state improving muscle reinnervation after nerve transection. [ABSTRACT FROM AUTHOR]