Search

Background: MicroRNAs (miRNAs) in Schwann cells (SCs) mediate peripheral nerve function. Ablating Dicer, a key gene in miRNA biogenesis, in SCs causes peripheral neuropathy. Exosomes from healthy SCs (SC-Exo) ameliorate diabetic peripheral neuropathy in part via miRNAs. Thus, using transgenic mice with conditional and inducible ablation of Dicer in proteolipid protein (PLP) expressing SCs (PLP-cKO), we examined whether SC-Exo could reduce peripheral neuropathy in PLP-cKO mice. Methods: PLP-cKO mice at the age of 16 weeks (8 week post-Tamoxifen) were randomly treated with SC-Exo or saline weekly for 8 weeks. Age-and sex-matched wild-type (WT) littermates were used as controls. Peripheral neurological functions, sciatic nerve integrity, and myelination were analyzed. Quantitative RT-PCR and Western blot analyses were performed to examine miRNA and protein expression in sciatic nerve tissues, respectively. Results: Compared to the WT mice, PLP-cKO mice exhibited a significant decrease in motor and sensory conduction velocities, thermal sensitivity, and motor coordination. PLP-cKO mice exhibited substantial demyelination and axonal damage of the sciatic nerve. Treatment of PLP-cKO mice with SC-Exo significantly ameliorated the peripheral neuropathy and sciatic nerve damage. PLP-cKO mice showed a substantial reduction in a set of Dicer-related miRNAs known to regulate myelination, axonal integrity, and inflammation such as miR-138, -146a and - 338 in the sciatic nerve. In addition, PLP-cKO mice exhibited significant reduction of myelin forming proteins, early growth response 2 (EGR2) and sex determining region Y-box10 (Sox10), but significantly increased myelination inhibitors, Notch1, c-Jun, and Sox2 and the axonal growth inhibitor phosphatase and tens in homolog (PTEN). However, SC-Exo treatment reversed the PLP-cKO altered miRNAs and proteins. Conclusion: This study demonstrates that exogenous SC-Exo ameliorate peripheral neuropathy induced by Dicer ablation in PLP expressing SCs. The therapeutic benefit may be mediated by the SC-Exo altered miRNAs and their targeted genes. [ABSTRACT FROM AUTHOR]

Background and Purpose: Fibromyalgia is a complex clinical disorder with an unknown aetiology, characterized by generalized pain and co‐morbid symptoms such as anxiety and depression. An imbalance of oxidants and antioxidants is proposed to play a pivotal role in the pathogenesis of fibromyalgia symptoms. However, the precise mechanisms by which oxidative stress contributes to fibromyalgia‐induced pain remain unclear. The transient receptor potential ankyrin 1 (TRPA1) channel, known as both a pain sensor and an oxidative stress sensor, has been implicated in various painful conditions. Experimental Approach: The feed‐forward mechanism that implicates reactive oxygen species (ROS) driven by TRPA1 was investigated in a reserpine‐induced fibromyalgia model in C57BL/6J mice employing pharmacological interventions and genetic approaches. Key Results: Reserpine‐treated mice developed pain‐like behaviours (mechanical/cold hypersensitivity) and early anxiety‐depressive‐like disorders, accompanied by increased levels of oxidative stress markers in the sciatic nerve tissues. These effects were not observed upon pharmacological blockade or global genetic deletion of the TRPA1 channel and macrophage depletion. Furthermore, we demonstrated that selective silencing of TRPA1 in Schwann cells reduced reserpine‐induced neuroinflammation (NADPH oxidase 1‐dependent ROS generation and macrophage increase in the sciatic nerve) and attenuated fibromyalgia‐like behaviours. Conclusion and Implications: Activated Schwann cells expressing TRPA1 promote an intracellular pathway culminating in the release of ROS and recruitment of macrophages in the mouse sciatic nerve. These cellular and molecular events sustain mechanical and cold hypersensitivity in the reserpine‐evoked fibromyalgia model. Targeting TRPA1 channels on Schwann cells could offer a novel therapeutic approach for managing fibromyalgia‐related behaviours. [ABSTRACT FROM AUTHOR]

Application of polyethylene glycol (PEG) to a peripheral nerve injury at the time of primary neurorrhaphy is thought to prevent Wallerian degeneration via direct axolemma fusion. The molecular mechanisms of nerve fusion and recovery are unclear. Our study tested the hypothesis that PEG alters gene expression in neural and muscular environments as part of its restorative properties. Lewis rats underwent unilateral sciatic nerve transection with immediate primary repair. Subjects were randomly assigned to receive either PEG treatment or standard repair at the time of neurorrhaphy. Samples of sciatic nerve distal to the injury and tibialis muscle at the site of innervation were harvested at 24 hours and 4 weeks postoperatively. Total RNA sequencing and subsequent bioinformatics analyses were used to identify significant differences in differentially expressed genes (DEGs) and their related biological pathways (p<0.05) in PEG-treated subjects compared to non-PEG controls. No significant DEGs were identified in PEG-treated sciatic nerve compared to controls after 24 hours, but 1,480 DEGs were identified in PEG-treated tibialis compared to controls. At 4 weeks, 918 DEGs were identified in PEG-treated sciatic nerve, whereas only 3 DEGs remained in PEG-treated tibialis compared to controls. DEGs in sciatic were mostly upregulated (79%) and enriched in pathways present during nervous system development and growth, whereas DEGs in muscle were mostly downregulated (77%) and related to inflammation and tissue repair. Our findings indicate that PEG application during primary neurorrhaphy leads to significant differential gene regulation in the neural and muscular environment that is associated with improved functional recovery in animals treated with PEG compared to sham non-PEG controls. A detailed understanding of key molecules underlying PEG function in recovery after peripheral nerve repair may facilitate amplification of PEG effects through systemic or focal treatments at the time of neurotmesis. [ABSTRACT FROM AUTHOR]

Developing long bones alter their shape while maintaining uniform cortical thickness via coordinated activity of bone)forming osteoblasts and bone-resorbing osteoclasts at periosteal and endosteal surfaces, a process we designate trans-pairing. Two types of trans-pairing shift cortical bone in opposite orientations: peri-forming trans-pairing (peri-t-p) increases bone marrow space and endo-forming trans-pairing (endo-t-p) decreases it, via paired activity of bone resorption and formation across the cortex. Here, we focused on endo-t-p in growing bones. Analysis of endo-t-p activity in the cortex of mouse fibulae revealed osteoclasts under the periosteum compressed by muscles, and expression of RANKL in periosteal cells of the cambium layer. Furthermore, mature osteoblasts were localized on the endosteum, while preosteoblasts were at the periosteum and within cortical canals. X-ray tomographic microscopy revealed the presence of cortical canals more closely associated with endo- than with peri-t-p. Sciatic nerve transection followed by muscle atrophy and unloading induced circumferential endo-t-p with concomitant spread of cortical canals. Such canals likely supply the endosteum with preosteoblasts from the periosteum under endo-t-p, allowing bone shape to change in response to mechanical stress or nerve injury. [ABSTRACT FROM AUTHOR]

Inhibiting aldose reductase (ALR2, AR) as well as maintaining a concomitant antioxidant (AO) activity via dual-acting agents may be a rational approach to prevent cellular glucotoxicity and at least delay the progression of diabetes mellitus (DM). This study was aimed at evaluating the dual-acting AR inhibitor (ARI) cemtirestat (CMTI) on tissue oxidative stress (OS) and carbonyl stress (CS) biomarkers in rats exposed to fructose alone (F) or fructose plus streptozotocin (D; type-2 diabetic). D and F rats were either untreated or treated daily with low- or high-dose CMTI, ARI drug epalrestat (EPA) or antioxidant stobadine (STB) for 14 weeks. Malondialdehyde (MDA), glutathione S-transferase (GST), nitric oxide synthase (NOS), and catalase (CAT) were increased in the sciatic nerve of F and D. These increases were attenuated by low doses of CMTI and STB in D, but exacerbated by low-dose EPA and high-dose CMTI in F. STB and CMTI and to a lesser extent EPA improved MDA, protein-carbonyl, GST and CAT in the hearts and lungs of F and D. CMTI and STB were more effective than EPA in improving the increased MDA and protein-carbonyl levels in the kidneys of F and especially D. CMTI ameliorated renal GST inhibition in D. In the lungs, hearts, and kidneys of F and D, the GSH to GSSG ratio decreased and caspase-3 activity increased, but partially resolved with treatments. In conclusion, CMTI with ARI/AO activity may be advantageous in overcoming OS, CS, and their undesirable consequences, with low dose efficacy and limited toxicity, compared to ARI or antioxidant alone. [ABSTRACT FROM AUTHOR]

The regeneration of peripheral nerves after injury is often slow and impaired, which may be associated with weakened and denervated muscles subsequently leading to atrophy. Adipose-derived stem cells (ADSCs) are often regarded as cell-based therapeutic candidate due to their regenerative potential. The study aims to assess the therapeutic efficacy of gene-modified ADSCs on sciatic nerve injury. We lentivirally transduced ADSCs with shRNA-TWIST1 and transplanted modified cells to rats undergoing sciatic nerve transection and repair. Results showed that TWIST1 knockdown accelerated functional recovery of rats with sciatic nerve injury as faster nerve conduction velocity and higher wire hang scores obtained by rats transplanted with TWIST1-silenced ADSCs than scramble ADSCs. Although the rats experienced degenerated axons and decreased myelin sheath thickness after sciatic nerve injury 8 weeks after operation, those transplanted with TWIST1-silenced ADSCs exhibited more signs of regenerated nerve fibers surrounded by newly formed myelin sheaths than those with scramble ADSCs. The rats transplanted with TWIST1-silenced ADSCs presented increased expressions of neurotrophic factors including neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) in the sciatic nerves than those with scramble ADSCs. These results suggest that genetically modifying TWIST1 in ADSCs could facilitate peripheral nerve repair after injury in a more efficient way than that with ADSCs alone. [ABSTRACT FROM AUTHOR]

Background At least 128,000 patients in the United States each year suffer from foot drop. This is a debilitating condition, marked by the inability to dorsiflex and/or evert the affected ankle. Such patients are rendered to a lifetime of relying on an ankle-foot orthosis (AFO) for walking and nighttime to prevent an equinovarus contracture. Methods This narrative review explores the differential diagnosis of foot drop, with a particular focus on clinical presentation and recovery, whether spontaneously or through surgery. Results Contrary to popular belief, foot drop can be caused by more than just insult to the common peroneal nerve at the fibular head (fibular tunnel). It is a common endpoint for a diverse spectrum of nerve injuries, which may explain its relatively high prevalence. From proximal to distal, these conditions include lumbar spine nerve root damage, sciatic nerve palsy at the sciatic notch, and common peroneal nerve injury at the fibular head. Each nerve condition is marked by a unique clinical presentation, frequency, likelihood for spontaneous recovery, and cadre of peripheral nerve techniques. Conclusion The ideal surgical technique for treating foot drop, other than neurolysis for compression, remains elusive as traditional peripheral nerve procedures have been marred by a wide spectrum of functional results. Based on a careful understanding of why past techniques have achieved limited success, we can formulate a working set of principles to help guide surgical innovation moving forward, such as fascicular nerve transfer. [ABSTRACT FROM AUTHOR]

Traumatic and postoperative hemorrhages are life-threatening complications. Ankaferd BloodStopper (ABS) is a potent topical hemostatic agent to stop bleeding. However, ABS is associated with nerve toxicity. The present study aimed to investigate the functional and structural neurodegenerative effects of ABS in a mouse model. A total of 30 male BALB/c mice, aged 6-8 weeks, were randomly divided into control group (no treatment), a sham group (treated with saline) and an experimental group (treated with ABS). In the saline and the ABS groups, the right sciatic nerve was surgically exposed and treated with saline or ABS, respectively. No surgical procedure was performed in the control group. On day 7 post-treatment, functional changes of the sciatic nerve were evaluated by a horizontal ladder rung walking task. Structural changes were assessed with immunohistochemistry. In the horizontal ladder rung walking test, the gait impairment was proportional to the severity of sciatic nerve damage, with the ABS group showing a significantly higher rate of errors than the control and saline groups. Immunohistochemistry demonstrated extensive degeneration and deformation in the axons and myelin sheath of the sciatic nerve in the ABS group. The results provide compelling evidence for the neurotoxicity of ABS. [ABSTRACT FROM AUTHOR]

The restoration of adequate function and sensation in nerves following an injury is often insufficient. Electrical stimulation (ES) applied during nerve repair can promote axon regeneration, which may enhance the likelihood of successful functional recovery. However, increasing operation time and complexity are associated with limited clinical use of ES. This study aims to better assess whether short-duration ES types (voltage mode vs. current mode) are able to produce enhanced regenerative activity following peripheral nerve repair in rat models. Wistar rats were randomly divided into 3 groups: no ES (control), 30-minute ES with a current pulse, and 30-minute ES with a voltage pulse. All groups underwent sciatic nerve transection and repair using a silicone tube to bridge the 6-mm gap between the stumps. In the 2 groups other than the control, ES was applied after the surgical repair. Outcomes were evaluated using electrophysiology, histology, and serial walking track analysis. Biweekly walking tracks test over 12 weeks revealed that subjects that underwent ES experienced more rapid functional improvement than subjects that underwent repair alone. Electrophysiological analysis of the newly intratubular sciatic nerve at week 12 revealed strong motor function recovery in rats that underwent 30-minute ES. Histologic analysis of the sciatic nerve and its tibial branch at 12 weeks demonstrated robust axon regrowth in all groups. Both types of short-duration ES applied during nerve repair can promote axon regrowth and enhance the chances of successful functional recovery. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance neurography (MRN) is increasingly used as a diagnostic tool for peripheral neuropathies. Quantitative measures enhance MRN interpretation but require nerve segmentation which is time-consuming and error-prone and has not become clinical routine. In this study, we applied neural networks for the automated segmentation of peripheral nerves. Methods: A neural segmentation network was trained to segment the sciatic nerve and its proximal branches on the MRN scans of the right and left upper leg of 35 healthy individuals, resulting in 70 training examples, via 5-fold cross-validation (CV). The model performance was evaluated on an independent test set of one-sided MRN scans of 60 healthy individuals. Results: Mean Dice similarity coefficient (DSC) in CV was 0.892 (95% confidence interval [CI]: 0.888–0.897) with a mean Jaccard index (JI) of 0.806 (95% CI: 0.799–0.814) and mean Hausdorff distance (HD) of 2.146 (95% CI: 2.184–2.208). For the independent test set, DSC and JI were lower while HD was higher, with a mean DSC of 0.789 (95% CI: 0.760–0.815), mean JI of 0.672 (95% CI: 0.642–0.699), and mean HD of 2.118 (95% CI: 2.047–2.190). Conclusion: The deep learning-based segmentation model showed a good performance for the task of nerve segmentation. Future work will focus on extending training data and including individuals with peripheral neuropathies in training to enable advanced peripheral nerve disease characterization. Relevance statement: The results will serve as a baseline to build upon while developing an automated quantitative MRN feature analysis framework for application in routine reading of MRN examinations. Key Points: Quantitative measures enhance MRN interpretation, requiring complex and challenging nerve segmentation. We present a deep learning-based segmentation model with good performance. Our results may serve as a baseline for clinical automated quantitative MRN segmentation. [ABSTRACT FROM AUTHOR]

Neuropathy is the most common disorder comprising peripheral nerve damage in diabetic patients. Prolonged hyperglycaemia and oxidative stress cause metabolic imbalance and are the key reasons for the development of diabetic neuropathy. Daidzein, a soy isoflavone possesses potent anti-hyperglycaemic and antioxidant activity. The present study aims to check the protective effect of Daidzein in diabetic neuropathy in rats. The experimental animal model involved induction of diabetes in rats by intraperitoneal injection of streptozotocin (55 mg/kg). Following confirmation of diabetes, the diabetic rats were subjected to oral treatment with varying doses of Daidzein (25, 50, and 100 mg/kg) and pregabalin (30 mg/kg) for a duration of 4 weeks, initiated 6 weeks after diabetes induction. Results indicated that Daidzein treatment led to a significant reduction in plasma glucose levels and an improvement in body weight among diabetic animals. Moreover, Daidzein demonstrated a positive impact on sensory functions, as evidenced by the effect on tail withdrawal and response latency. Mechanical hyperalgesia and allodynia, common symptoms of diabetic neuropathy, were also significantly reduced with both Daidzein and pregabalin treatment. Notably, nerve conduction velocities exhibited improvement following the administration of Daidzein and pregabalin. Further investigation into the molecular mechanisms revealed that Daidzein treatment resulted in a notable enhancement of antioxidant enzyme levels and a reduction in the overexpression of NOX-4 in the sciatic nerve. This suggests that Daidzein's therapeutic effect is associated with the inhibition of oxidative stress via NOX-4. In summary, the findings of study suggests that, Daidzein treatment significantly attenuated diabetic neuropathy by inhibiting oxidative stress via NOX-4 inhibition. [ABSTRACT FROM AUTHOR]

Background: Patients suffering from neurological symptoms after COVID-19 vaccination (post-COVID-19 vaccination syndrome (PCVS)) have imposed an increasing challenge on medical practice, as diagnostic precision and therapeutic options are lacking. Underlying autoimmune dysfunctions, including autoantibodies, have been discussed in neurological disorders after SARSCoV-2 infection and vaccination. Here, we describe the frequency and targets of autoantibodies against peripheral nervous system tissues in PCVS. Methods: Sera from50 PCVS patients with peripheral neurological symptoms after COVID-19 vaccination and 35 vaccinated healthy controls were used in this study. IgG autoreactivity was measured via indirect immunofluorescence assays on mouse sciatic nerve teased fibers. The frequencies of autoantibodies were compared between groups using Fisher's exact test. Serum anti-ganglioside antibodies were measured in ganglioside blots. Autoantibody target identification was performed using immunoprecipitation coupled to mass spectrometry. Subsequent target confirmation was conducted via cell-based assays and ELISA. Results: Compared with controls, PCVS patients had a significantly greater frequency of autoantibodies against peripheral nervous system structures (9/50 (18%) vs 1/35(3%); p=0.04). Autoantibodies bound to paranodes (n=5), axons (n=4), Schmidt-Lanterman incisures (n=2) and Schwann cell nuclei (n=1). Conversely, antibodies against gangliosides were absent in PCVS patients. Target identification and subsequent confirmation revealed various subunits of neurofilaments as well as DFS-70 as autoantibody epitopes. Conclusion: Our data suggest that autoantibodies against nervous system tissue could be relevant in PCVS patients. Autoantibodies against neurofilaments and cell nuclei with so far non-established links to this disease spectrum should be further elucidated to determine their biomarker potential. [ABSTRACT FROM AUTHOR]

Myelin sheath plays important roles in information conduction and nerve injury repair in the peripheral nerve system (PNS). Enhancing comprehension of the structure and components of the myelin sheath in the PNS during development would contribute to a more comprehensive understanding of the developmental and regenerative processes. In this research, the structure of sciatic nerve myelin sheath in C57BL/6 mice from embryonic day 14 (E14) to postnatal 12 months (12M) was observed with transmission electron microscopy. Myelin structure appeared in the sciatic nerve as early as E14, and the number and thickness of myelin lamellar gradually increased with the development until 12M. Transcriptome analysis was performed to show the expressions of myelin‐associated genes and transcriptional factors involved in myelin formation. The genes encoding myelin proteins (Mag, Pmp22, Mpz, Mbp, Cnp and Prx) showed the same expression pattern, peaking at postnatal day 7 (P7) and P28 after birth, whereas the negative regulators of myelination (c‐Jun, Tgfb1, Tnc, Cyr61, Ngf, Egr1, Hgf and Bcl11a) showed an opposite expression pattern. In addition, the expression of myelin‐associated proteins and transcriptional factors was measured by Western blot and immunofluorescence staining. The protein expressions of MAG, PMP22, MPZ, CNPase and PRX increased from E20 to P14. The key transcriptional factor c‐Jun co‐localized with the Schwann cells Marker S100β and decreased after birth, whereas Krox20/Egr2 increased during development. Our data characterized the structure and components of myelin sheath during the early developmental stages, providing insights for further understanding of PNS development. [ABSTRACT FROM AUTHOR]

Background: Injuries of the proximal attachment of the hamstring muscles are common. The present study aimed to investigate the relationship of the proximal attachment of the hamstring muscles with neighboring structures comprehensively. Methods: A total of 97 hemipelvis from 66 cryopreserved specimens were evaluated via ultrasound, anatomical and histological samples. Results: The proximal attachment of the hamstring muscles presents a hyperechogenic line surrounding the origin of the semimembranosus and the long head of the biceps femoris muscles, as well as another hyperechogenic line covering the sciatic nerve. The anatomical and histological study confirms the ultrasound results and shows different layers forming the sacrotuberous ligament. Furthermore, it shows that the proximal attachment of the semimembranosus muscle has a more proximal origin than the rest of the hamstring muscles. Moreover, this muscle shares fibers with the long head of the biceps femoris muscle and expands to the adductor magnus muscle. The histological analysis also shows the dense connective tissue of the retinaculum covering the long head of the biceps femoris and semimembranosus muscles, as well as the expansion covering the sciatic nerve. Conclusions: These anatomical relationships could explain injuries at the origin of the hamstring muscles. [ABSTRACT FROM AUTHOR]

Neuritin, also known as candidate plasticity gene 15 (CPG15), was first identified as one of the activity‐dependent gene products in the brain. Previous studies have been reported that Neuritin induces neuritogenesis, neurite arborization, neurite outgrowth and synapse formation, which are involved in the development and functions of the central nervous system. However, the role of Neuritin in peripheral nerve injury is still unknown. Given the importance and necessity of Schwann cell dedifferentiation response to peripheral nerve injury, we aim to investigate the molecular mechanism of Neuritin steering Schwann cell dedifferentiation during Wallerian degeneration (WD) in injured peripheral nerve. Herein, using the explants of sciatic nerve, an ex vivo model of nerve degeneration, we provided evidences indicating that Neuritin vividly accelerates Schwann cell dedifferentiation. Moreover, we found that Neuritin promotes Schwann cell demyelination as well as axonal degeneration, phagocytosis, secretion capacity. In summary, we first described Neuritin acts as a positive regulator for Schwann cell dedifferentiation and WD after peripheral nerve injury. [ABSTRACT FROM AUTHOR]

Peripheral neuropathy (PN) is a severe and frequent complication of obesity, prediabetes, and type 2 diabetes characterized by progressive distal-to-proximal peripheral nerve degeneration. However, a comprehensive understanding of the mechanisms underlying PN, and whether these mechanisms change during PN progression, is currently lacking. Here, gene expression data were obtained from distal (sciatic nerve; SCN) and proximal (dorsal root ganglia; DRG) injury sites of a high-fat diet (HFD)-induced mouse model of obesity/prediabetes at early and late disease stages. Self-organizing map and differentially expressed gene analyses followed by pathway enrichment analysis identified genes and pathways altered across disease stage and injury site. Pathways related to immune response, inflammation, and glucose and lipid metabolism were consistently dysregulated with HFD-induced PN, irrespective of injury site. However, regulation of oxidative stress was unique to the SCN while dysregulated Hippo and Notch signaling were only observed in the DRG. The role of the immune system and inflammation in disease progression was supported by an increase in the percentage of immune cells in the SCN with PN progression. Finally, when comparing these data to transcriptomic signatures from human patients with PN, we observed conserved pathways related to metabolic dysregulation across species, highlighting the translational relevance of our mouse data. Our findings demonstrate that PN is associated with distinct site-specific molecular re-programming in the peripheral nervous system, identifying novel, clinically relevant therapeutic targets. [ABSTRACT FROM AUTHOR]

Extrarenal extracranial malignant rhabdoid tumour (MRT) is a rare and highly aggressive tumour representing <1% of paediatric soft tissue malignancies. Only a few cases of MRT of the thigh arising from the sciatic nerve have been reported in medical literature to date. A 5-year-old girl presented with progressively increasing painless lump in the posterior aspect of the left thigh. A contrast-enhanced magnetic resonance imaging (MRI) of the left thigh showed a 4.7 × 5 × 10.5 cm well-marginated, lobulated, homogeneously enhancing lesion in the posterior compartment of the left thigh along the course of the sciatic nerve. She underwent en bloc excision of the left sciatic nerve tumour and end-to-end anastomosis of the left sciatic nerve with a right sural nerve graft. Histopathological and immunohistochemical examination of the surgical specimen revealed a malignant rhabdoid tumour. INI-1 immunoexpression was lost in the tumour cells. The metastatic workup was essentially normal. Subsequently, she received post-operative radiotherapy to the tumour bed (50.4 Gray in 28 fractions over 5.5 weeks) followed by six cycles of multiagent chemotherapy with ICE (Ifosfamide, Carboplatin, and Etoposide) regimen. On the last follow-up visit, 20 months after surgery, she was in complete clinical and radiological response. Aggressive multimodality management comprising radical resection of tumour, post-operative radiotherapy to the tumour bed, and multiagent chemotherapy with ICE regimen can lead to favourable outcomes in patients with this rare tumour. [ABSTRACT FROM AUTHOR]

Peripheral nerve modulation via electrical stimulation shows promise for treating several diseases, but current approaches lack selectivity, leading to side effects. Exploring selective neuromodulation with commercially available nerve cuffs is impractical due to their high cost and limited spatial resolution. While custom cuffs reported in the literature achieve high spatial resolutions, they require specialized microfabrication equipment and significant effort to produce even a single design. This inability to rapidly and cost-effectively prototype novel cuff designs impedes research into selective neuromodulation therapies in acute studies. To address this, we developed a reproducible method to easily create multi-channel epineural nerve cuffs for selective fascicular neuromodulation. Leveraging commercial flexible printed circuit (FPC) technology, we created cuffs with high spatial resolution (50 μm) and customizable parameters like electrode size, channel count, and cuff diameter. We designed cuffs to accommodate adult mouse or rat sciatic nerves (300–1500 μm diameter). We coated the electrodes with PEDOT:PSS to improve the charge injection capacity. We demonstrated selective neuromodulation in both rats and mice, achieving preferential activation of the tibialis anterior (TA) and lateral gastrocnemius (LG) muscles. Selectivity was confirmed through micro-computed tomography (μCT) and quantified through a selectivity index. These results demonstrate the potential of this fabrication method for enabling selective neuromodulation studies while significantly reducing production time and costs compared to traditional approaches. [ABSTRACT FROM AUTHOR]

Anethole is a terpenoid with antioxidant, anti-inflammatory, and neuronal blockade effects, and the present work was undertaken to study the neuroprotective activity of anethole against diabetes mellitus (DM)-induced neuropathy. Streptozotocin-induced DM rats were used to investigate the effects of anethole treatment on morphological, electrophysiological, and biochemical alterations of the sciatic nerve (SN). Anethole partially prevented the mechanical hyposensitivity caused by DM and fully prevented the DM-induced decrease in the cross-sectional area of the SN. In relation to electrophysiological properties of SN fibers, DM reduced the frequency of occurrence of the 3rd component of the compound action potential (CAP) by 15%. It also significantly reduced the conduction velocity of the 1st and 2nd CAP components from 104.6 ± 3.47 and 39.8 ± 1.02 to 89.9 ± 3.03 and 35.4 ± 1.56 m/s, respectively, and increased the duration of the 2nd CAP component from 0.66 ± 0.04 to 0.82 ± 0.09 ms. DM also increases oxidative stress in the SN, altering values related to thiol, TBARS, SOD, and CAT activities. Anethole was capable of fully preventing all these DM electrophysiological and biochemical alterations in the nerve. Thus, the magnitude of the DM-induced neural effects seen in this work, and the prevention afforded by anethole treatment, place this compound in a very favorable position as a potential therapeutic agent for treating diabetic peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Peripheral nerve defect are common clinical problem caused by trauma or other diseases, often leading to the loss of sensory and motor function in patients. Autologous nerve transplantation has been the gold standard for repairing peripheral nerve defects, but its clinical application is limited due to insufficient donor tissue. In recent years, the application of tissue engineering methods to synthesize nerve conduits for treating peripheral nerve defect has become a current research focus. This study introduces a novel approach for treating peripheral nerve defects using a tissue‐engineered PLCL/SF/NGF@TA‐PPy‐RGD conduit. The conduit was fabricated by combining electrospun PLCL/SF with an NGF‐loaded conductive TA‐PPy‐RGD gel. The gel, synthesized from RGD‐modified tannic acid (TA) and polypyrrole (PPy), provides growth anchor points for nerve cells. In vitro results showed that this hybrid conduit could enhance PC12 cell proliferation, migration, and reduce apoptosis under oxidative stress. Furthermore, the conduit activated the PI3K/AKT signalling pathway in PC12 cells. In a rat model of sciatic nerve defect, the PLCL/SF/NGF@TA‐PPy‐RGD conduit significantly improved motor function, gastrocnemius muscle function, and myelin sheath axon thickness, comparable to autologous nerve transplantation. It also promoted angiogenesis around the nerve defect. This study suggests that PLCL/SF/NGF@TA‐PPy‐RGD conduits provide a conducive environment for nerve regeneration, offering a new strategy for peripheral nerve defect treatment, this study provided theoretical basis and new strategies for the research and treatment of peripheral nerve defect. [ABSTRACT FROM AUTHOR]

Objectives: This work investigated the acute antinociceptive effect of a synthetic chalcone, 4-dimethylamino chalcone (DMAC), as well as its effects on vincristine-induced peripheral neuropathy (VIPN) in mice. Methods: The inhibitory activity of myeloperoxidase was assessed by measuring HOCl formation. Formalin and hot plate tests were used to study the acute antinociceptive effect of DMAC. VIPN was induced through the administration of vincristine sulphate (0.1 mg/kg, i.p., 14 days). Then, DMSO, DMAC (10 or 30 mg/kg; i.p.), or pregabalin (10 mg/kg, i.p.) were administered for 14 consecutive days. Thermal hyperalgesia and mechanical allodynia were evaluated before and after VIPN induction and on days 1, 3, 7, and 14 of treatment. Neurodegeneration and neuroinflammation were assessed through immunohistochemistry for NF200, iNOS, and arginase-1 within the sciatic nerve. Key findings: DMAC inhibited myeloperoxidase activity in vitro and presented an acute antinociceptive effect in both formalin and hot plate tests, with the involvement of muscarinic and opioid receptors. Treatment with 30 mg/kg of DMAC significantly attenuated thermal hyperalgesia and mechanical allodynia and prevented macrophage proinflammatory polarisation in VIPN mice. Conclusions: Our results show that DMAC, acting through different mechanisms, effectively attenuates VIPN. [ABSTRACT FROM AUTHOR]

Silibinin (SBN), a sirtuin 1 (SIRT1) activator, has been evaluated for its anti-inflammatory activity in many inflammatory diseases. However, its role in diabetes-induced peripheral neuropathy (DPN) remains unknown. The SIRT1 activation convalesces nerve functions by improving mitochondrial biogenesis and mitophagy. DPN was induced by streptozotocin (STZ) at a dose of 55 mg/kg, i.p. in the male SD rats whereas neurotoxicity was induced in Neuro2A cells by 30 mM (high glucose) glucose. Neurobehavioural (nerve conduction velocity and nerve blood flow) western blot, immunohistochemistry, and immunocytochemistry were performed to evaluate the protein expression and their cellular localisation. Two-week SBN treatment improved neurobehavioural symptoms, SIRT1, PGC-1α, and TFAM expression in the sciatic nerve and HG insulted N2A cells. It has also maintained the mitophagy by up-regulating PARL, PINK1, PGAM5, LC3 level and provided antioxidant defence by upregulating Nrf2. SBN has shown neuroprotective potential in DPN through SIRT1 activation and antioxidant mechanism. [ABSTRACT FROM AUTHOR]

Introduction/Aims: The development of high‐resolution ultrasound (HRUS) has enabled the depiction of peripheral nerve microanatomy in vivo. This study compared HRUS fascicle differentiation to the structural depiction in histological cross‐sections (HCS). Methods: A human cadaveric sciatic nerve was marked with 10 surgical sutures, and HRUS image acquisition was performed with a 22‐MHz probe. The nerve was excised and cut into five segments for HCS preparation. Selected HCS were cross‐referenced to HRUS, with sutures to improve orientation. Sciatic nerve and fascicle contouring were performed to assess nerve and fascicular cross‐sectional area (CSA), fascicle count, and interfascicular distances. Three groups were defined based on HRUS fascicle differentiation in comparison to HCS, namely single fascicle (SF), fascicular cluster (FC), and no depiction (ND) group. Results: On cross‐referenced HRUS to HCS images, 58% of fascicles were differentiated. On HRUS, significantly larger fascicle CSA and smaller fascicle count were observed compared with HCS. Group analysis showed that 41% of fascicles were defined as SF, 47% as FC, and 12% as ND. The mean fascicle CSA in the ND group was 0.05 mm2. Compared with the SF, the FC had significantly larger fascicle CSA (1.2 ± 0.7 vs. 0.6 ± 0.4 mm2; p <.001) and shorter interfascicular distances (0.1 ± 0.04 vs. 0.5 ± 0.3 μm; p <.001). Discussion: While HRUS can depict fascicular anatomy, only half of the fascicles visualized on HRUS directly correspond to single fascicles observed on HCS. The amount of interfascicular epineurium appears to influence the ability of HRUS to differentiate individual fascicles. [ABSTRACT FROM AUTHOR]

Complicated peripheral nerve injuries or defects, especially at branching sites, remain a prominent clinical challenge after the application of different treatment strategies. Current nerve grafts fail to match the expected shape and size for delicate and precise branched nerve repair on a case-by-case basis, and there is a lack of geometrical and microscale regenerative navigation. In this study, we develop a sugar painting-inspired individualized multilevel epi-/peri-/endoneurium-mimetic device (SpinMed) to customize natural cues, featuring a selectively protective outer sheath and an instructive core, to support rapid vascular reconstruction and consequent efficient neurite extension along the defect area. The biomimetic perineurium dictates host-guest crosslinking in which new vessels secrete multimerin 1 binding to the fibroin filler surface as an anchor, contributing to the biological endoneurium that promotes Schwann cell homing and remyelination. SpinMed implantation into rat sciatic nerve defects yields a satisfactory outcome in terms of structural reconstruction, with sensory and locomotive function restoration. We further customize SpinMed grafts based on anatomy and digital imaging, achieving rapid repair of the nerve trunk and branches superior to that achieved by autografts and decellularized grafts in a specific beagle nerve defect model, with reliable biosafety. Overall, this intelligent art-inspired biomimetic design offers a facile way to customize sophisticated high-performance nerve grafts and holds great potential for application in translational regenerative medicine. Nerve grafts often fail to match the expected shape and size for branched nerve repair. Here, the authors fabricate a sugar painting-inspired individualized multilevel epi-/peri-/endoneurium-mimetic device to achieve efficient regeneration of neural fibers. [ABSTRACT FROM AUTHOR]

Background: Sciatic nerve repair becomes a focus of research in neurological aspect to restore the normal physical ability of the animal to stand and walk. Tissue engineered nerve grafts (TENGs) provide a promising alternative therapy for regeneration of large gap defects. The present study investigates the regenerative capacity of PRP, ADSCs, and PRP mixed ADSCs on a long sciatic nerve defect (40-mm) bridged by a polyglycolic polypropylene (PGA-PRL) mesh which acts as a neural scaffold. Materials and methods: The study was conducted on 12 adult male mongrel dogs that were randomly divided into 4 groups: Group I (scaffold group); where the sciatic defect was bridged by a (PGA-PRL) mesh only while the mesh was injected with ADSCs in Group II (ADSCs group), PRP in Group III (PRP group). Mixture of PRP and ADSCs was allocated in Group IV (PRP + ADSCs group). Monthly, all animals were monitored for improvement in their gait and a numerical lameness score was recorded for all groups. 6 months-post surgery, the structural and functional recovery of sciatic nerve was evaluated electrophysiologically, and on the level of gene expression, and both sciatic nerve and the gastrocnemius muscle were evaluated morphometrically, histopathologically. Results: Numerical lameness score showed improvement in the motor activities of both Group II and Group III followed by Group IV and the scaffold group showed mild improvement even after 6 months. Histopathologically, all treated groups showed axonal sprouting and numerous regenerated fascicles with obvious angiogenesis in proximal cut, and distal portion where Group IV exhibited a significant remyelination with the MCOOL technique. The regenerative ratio of gastrocnemius muscle was 23.81%, 56.68%, 52.06% and 40.69% for Group I, II, III and IV; respectively. The expression of NGF showed significant up regulation in the proximal portion for both Group III and Group IV (P ≤ 0.0001) while Group II showed no significant difference. PDGF-A, and VEGF expressions were up-regulated in Group II, III, and IV whereas Group I showed significant down-regulation for NGF, PDGF-A, and VEGF (P ≤ 0.0001). Conclusion: ADSCs have a great role in restoring the damaged nerve fibers by secreting several types of growth factors like NGF that have a proliferative effect on Schwann cells and their migration. In addition, PRP therapy potentiates the effect of ADSCs by synthesis another growth factors such as PDGF-A, VEGF, NGF for better healing of large sciatic gap defects. [ABSTRACT FROM AUTHOR]

Background: Diabetic neuropathy (DN) is recognized as a significant complication arising from diabetes mellitus (DM). Pathogenesis of DN is accelerated by endoplasmic reticulum (ER) stress, which inhibits autophagy and contributes to disease progression. Autophagy is a highly conserved mechanism crucial in mitigating cell death induced by ER stress. Chrysin, a naturally occurring flavonoid, can be found abundantly in honey, propolis, and various plant extracts. Despite possessing advantageous attributes such as being an antioxidant, anti-allergic, anti-inflammatory, anti-fibrotic, and anticancer agent, chrysin exhibits limited bioavailability. The current study aimed to produce a more bioavailable form of chrysin and discover how administering chrysin could alter the neuropathy induced by Alloxan in male rats. Methods: Chrysin was formulated using PEGylated liposomes to boost its bioavailability and formulation. Chrysin PEGylated liposomes (Chr-PLs) were characterized for particle size diameter, zeta potential, polydispersity index, transmission electron microscopy, and in vitro drug release. Rats were divided into four groups: control, Alloxan, metformin, and Chr-PLs. In order to determine Chr- PLs' antidiabetic activity and, by extension, its capacity to ameliorate DN, several experiments were carried out. These included measuring acetylcholinesterase, fasting blood glucose, insulin, genes dependent on autophagy or stress in the endoplasmic reticulum, and histopathological analysis. Results: According to the results, the prepared Chr-PLs exhibited an average particle size of approximately 134 nm. They displayed even distribution of particle sizes. The maximum entrapment efficiency of 90.48 ± 7.75% was achieved. Chr-PLs effectively decreased blood glucose levels by 67.7% and elevated serum acetylcholinesterase levels by 40% compared to diabetic rats. Additionally, Chr-PLs suppressed the expression of ER stress-related genes (ATF-6, CHOP, XBP-1, BiP, JNK, PI3K, Akt, and mTOR by 33%, 39.5%, 32.2%, 44.4%, 40.4%, 39.2%, 39%, and 35.9%, respectively). They also upregulated the miR-301a-5p expression levels by 513% and downregulated miR-301a-5p expression levels by 65%. They also boosted the expression of autophagic markers (AMPK, ULK1, Beclin 1, and LC3-II by 90.3%, 181%, 109%, and 78%, respectively) in the sciatic nerve. The histopathological analysis also showed that Chr-PLs inhibited sciatic nerve degeneration. Conclusion: The findings suggest that Chr-PLs may be helpful in the protection against DN via regulation of ER stress and autophagy. [ABSTRACT FROM AUTHOR]

3D printing has been widely used for on-demand prototyping of complex three-dimensional structures. In biomedical applications, PEDOT:PSS has emerged as a promising material in versatile bioelectronics due to its tissue-like mechanical properties and suitable electrical properties. However, previously developed PEDOT:PSS inks have not been able to fully utilize the advantages of commercial 3D printing due to its long post treatment times, difficulty in high aspect ratio printing, and low conductivity. We propose a one-shot strategy for the fabrication of PEDOT:PSS ink that is able to simultaneously achieve on-demand biocompatibility (no post treatment), structural integrity during 3D printing for tall three-dimensional structures, and high conductivity for rapid-prototyping. By using ionic liquid-facilitated PEDOT:PSS colloidal stacking induced by a centrifugal protocol, a viscoplastic PEDOT:PSS-ionic liquid colloidal (PILC) ink was developed. PILC inks exhibit high-aspect ratio vertical stacking, omnidirectional printability for generating suspended architectures, high conductivity (~286 S/cm), and high-resolution printing (~50 µm). We demonstrate the on-demand and versatile applicability of PILC inks through the fabrication of 3D circuit boards, on-skin physiological signal monitoring e-tattoos, and implantable bioelectronics (opto-electrocorticography recording, low voltage sciatic nerve stimulation and recording from deeper brain layers via 3D vertical spike arrays). Conventional PEDOT:PSS inks for electrical interfacing with ex-vivo and in-vivo systems are limited by poor rheological and conductive properties. Here, the authors show a one-shot strategy to fabricate 3D printable and biocompatible PEDOT:PSS-ionic liquid colloidal ink for bioelectronics with 2D and 3D structures. [ABSTRACT FROM AUTHOR]

Electroactive materials are increasingly recognized for their efficacy in promoting the repair of peripheral nerve injury. However, the mechanism by which electroactive materials promote peripheral nerve regeneration by modulating the immune microenvironment remains incompletely explored. In this study, a PVDF/PLCL/PEDOT artificial peripheral nerve conduit with dual electroactivity by integrating piezoelectric properties and electrical conductivity is constructed. The electroactive conduit exhibited excellent spontaneous electrical and conductive properties, superior suture resistance and anti‐twisting properties. Detailed in vitro cell experiments and in vivo animal experiments are conducted, revealing that the electroactive nerve conduit can effectively promote rat sciatic nerve regeneration while facilitating reconstruction of both nerve conduction function and motor function. Furthermore, the underlying mechanism in depth is investigated and found that the electroactive material can regulate the immune microenvironment by activating the PI3K/AKT‐Nrf2 signaling pathway, thereby promoting macrophage polarization toward M2 anti‐inflammatory phenotype. This subsequently facilitated Schwann cell recruitment and myelin formation through mediation of the macrophage paracrine system. Importantly, blocking immune signaling pathways diminished the effectiveness of the electroactive nerve conduit in promoting nerve repair. The work elucidated how electroactive materials modulate immune microenvironment to positively impact peripheral nerve repair, highlighting the critical role of immune modulation in peripheral nerve repair. [ABSTRACT FROM AUTHOR]

Background: Implantable vagus nerve stimulation is a promising approach for restoring autonomic cardiovascular functions after heart transplantation. For successful treatment a system should have multiple electrodes to deliver precise stimulation and complex neuromodulation patterns. Methods: This paper presents an implantable multi-channel stimulation system for vagal-cardiac neuromodulation studies in swine species. The system comprises an active electrode array implant percutaneously connected to an external wearable controller. The active electrode array implant has an integrated stimulator ASIC mounted on a ceramic substrate connected to an intraneural electrode array via micro-rivet bonding. The implant is silicone encapsulated for biocompatibility and implanted lifetime. The stimulation parameters are remotely transmitted via a Bluetooth telemetry link. Results: The size of the encapsulated active electrode array implant is 8 mm × 10 mm × 3 mm. The stimulator ASIC has 10-bit current amplitude resolution and 16 independent output channels, each capable of delivering up to 550 µA stimulus current and a maximum voltage of 20 V. The active electrode array implant was subjected to in vitro accelerated lifetime testing at 70 °C for 7 days with no degradation in performance. After over 2 h continuous stimulation, the surface temperature change of the implant was less than 0.5 °C. In addition, in vivo testing on the sciatic nerve of a male Göttingen minipig demonstrated that the implant could effectively elicit an EMG response that grew progressively stronger on increasing the amplitude of the stimulation. Conclusions: The multi-channel stimulator is suitable for long term implantation. It shows potential as a useful tool in vagal-cardiac neuromodulation studies in animal models for restoring autonomic cardiovascular functions after heart transplantation. [ABSTRACT FROM AUTHOR]

Background/aim: In the literature, almost all of the nerve conduits proposed for obtaining better nerve recovery were applied as graft materials. In this study, we aimed to propose a new nerve conduit model with a flap pattern and evaluate the effect of a pedicled vascularized jejunal flap on nerve regeneration after wrapping it around a sciatic nerve. Materials and methods: A total of 90 Wistar albino rats were randomly divided into nine groups with 10 rats in each. The first three groups constituted the control groups, whereas Groups 4-6 were the jejunum conduit (JC)-applied groups. A mucosa-resected JC (MRJC) was applied in Groups 7 and 8. Epineurial neurorrhaphy was performed in Groups 1, 4, and 7; repair with a nerve graft was applied in Groups 2, 5, and 8; and a 1-cm-long nerve defect was created in Groups 3, 6, and 9. After 2 months of follow-up, nerve regeneration was assessed by statistical analyses of the Sciatic Functional Index (SFI) and histopathological evaluation. Results: The MRJC groups had significantly better results in terms of SFI (p = 0.005). Statistical differences in axonal degeneration, axonal density, myelination, and disorganization were found between all control groups and MRJC groups (p = 0.022, p = 0.001, p = 0.001, and p = 0.039, respectively). Conclusion: In this study, the feasibility of wrapping around the nerve repair zones of pedicled autologous flaps designed in a tubular fashion was observed in a small rat model. The findings must be further validated with larger animals before clinical testing. [ABSTRACT FROM AUTHOR]

In this study, the effects of electrode porosity on nerve regeneration and functional recovery after sciatic nerve transection in rats was investigated. A sieve-type neural electrode with 70% porosity was designed and compared with an electrode with 30% porosity. Electrodes were fabricated from photosensitive polyimide and implanted into the transected sciatic nerves. Motor function recovery was evaluated using the Sciatic Function Index. The number of active channels and their signal quality were recorded and analyzed to assess the sensory neural signal acquisition. Electrical impedance spectroscopy was used to evaluate the electrode performance. The group implanted with the 70% porosity electrode demonstrated significantly enhanced nerve regeneration and motor function recovery, approaching control group levels by the fifth week. In contrast, the group with the 30% porosity electrode exhibited limited improvement. Immunohistochemical analysis confirmed extensive nerve fiber growth within the 70% porous structure. Moreover, the 70% porosity electrode consistently acquired neural signals from more channels compared to the 30% porosity electrode, demonstrating its superior performance in sensory signal detection. These findings emphasize the importance of optimizing electrode porosity in the development of advanced neural interfaces, with the potential to enhance clinical outcomes in peripheral nerve repair and neuroprosthetic applications. [ABSTRACT FROM AUTHOR]

Background: Sciatic nerve palsy is a rare but devastating complication following total hip arthroplasty (THA). While the use of the direct anterior approach is increasing, limited data exist regarding sciatic nerve palsy and surgical approach. The purpose of this study was to determine the factors and outcomes associated with sciatic nerve palsy (SNP) after THA. Methods: A retrospective analysis was performed at a single institution of 7 SNP that occurred in 4045 THA via direct anterior approach and 10 SNP in 8854 THA via posterior approach, being operated between 01 January 2017 and 12 December 2021. SNP patients were matched 1:5 to patients without SNP. Medical records were reviewed for demographics including age, gender, body mass index (BMI), comorbidities, and preoperative indication. Additional workup of SNP patients including advanced imaging and reoperation were documented. Recovery grades were assigned to all SNP patients at most recent clinical follow-up. Results: 5 of the SNP were complete and 12 partial. They occurred as frequently with the direct anterior (0.17%) and posterior approach (0.11%, p = 0.5). The presence of femur cables and reoperations were associated with SNP (p = 0.04 and p = 0.002, respecitvely). Age, gender, BMI, comorbidities, and surgical indication had no effect on SNP. 4 of the 17 affected patients had almost complete recovery at latest follow-up. Conclusions: The incidence of SNP was similar in direct anterior and posterior approach. Surgeons should counsel patients regarding the risks of SNP regardless of the used approach. [ABSTRACT FROM AUTHOR]

Background: Nerve injury is one of the most serious complications of total hip arthroplasty (THA). It is suspected to be a result from nerve compression or direct injury caused by an acetabular retractor. The anatomical relationship between the acetabular rim and the femoral and sciatic nerves, including hip motion, has not been investigated. This study aimed to identify the optimal position for retractor insertion during THA to prevent nerve damage. Methods: A total of 28 hip joints from 14 freshly frozen cadavers were used. Using an anterolateral approach, each cadaver was immobilised in the lateral decubitus position and deployed to measure the distance between the nerves and the acetabular rim, while the hip joint was changed to the extension, neutral, and flexion positions. Results: Three femoral nerves were closest to the anterior margin of the acetabulum at 90° and 120° of extension and farthest away at 30° of flexion. The sciatic nerve was closest to the posterior margin of the acetabulum at 90° and 120° of flexion and farthest away at 30° and 150° of extension compared with the other points. Conclusions: To prevent nerve damage during THA, we suggest that the retractor be inserted at the points where the nerves are the farthest away, such as at 30° and 150°. The femoral and sciatic nerves vary in their movements depending on the hip position. Therefore, the safe insertion of a retractor is recommended for hip flexion of the femoral nerve and extension of the sciatic nerve. Additionally, it is important to carefully insert the retractor along the acetabular margin without penetrating the joint capsule. Overall, this study provides valuable insights into the anatomical location and movement of the femoral and sciatic nerves in relation to hip motion and can help inform surgical techniques for safer THA. [ABSTRACT FROM AUTHOR]

Despite recent advancements in peripheral nerve regeneration, the creation of nerve conduits with chemical and physical cues to enhance glial cell function and support axonal growth remains challenging. This study aimed to assess the impact of electrical stimulation (ES) using a conductive nerve conduit on sciatic nerve regeneration in a rat model with transection injury. The study involved the fabrication of conductive nerve conduits using silk fibroin and Au nanoparticles (AuNPs). Collagen hydrogel loaded with green fluorescent protein (GFP)-positive adipose-derived mesenchymal stem cells (ADSCs) served as the filling for the conduit. Both conductive and non-conductive conduits were applied with and without ES in rat models. Locomotor recovery was assessed using walking track analysis. Histological evaluations were performed using H&E, luxol fast blue staining and immunohistochemistry. Moreover, TEM analysis was conducted to distinguish various ultrastructural aspects of sciatic tissue. In the ES + conductive conduit group, higher S100 (p < 0.0001) and neurofilament (p < 0.001) expression was seen after 6 weeks. Ultrastructural evaluations showed that conductive scaffolds with ES minimized Wallerian degeneration. Furthermore, the conductive conduit with ES group demonstrated significantly increased myelin sheet thickness and decreased G. ratio compared to the autograft. Immunofluorescent images confirmed the presence of GFP-positive ADSCs by the 6th week. Locomotor recovery assessments revealed improved function in the conductive conduit with ES group compared to the control group and groups without ES. These results show that a Silk/AuNPs conduit filled with ADSC-seeded collagen hydrogel can function as a nerve conduit, aiding in the restoration of substantial gaps in the sciatic nerve with ES. Histological and locomotor evaluations indicated that ES had a greater impact on functional recovery compared to using a conductive conduit alone, although the use of conductive conduits did enhance the effects of ES. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the utility of using high-frequency ultrasound to non-invasively track the degenerative process in a rat model of peripheral nerve injury. Primary analyses explored spatial and temporal changes in quantitative backscatter coefficient (BSC) spectrum-based outcomes and B-mode textural outcomes, using gray level co-occurrence matrices (GLCMs), during the progressive transition from acute to chronic injury. As secondary analyses, correlations among GLCM and BSC spectrum-based parameters were evaluated, and immunohistochemistry were used to suggest a structural basis for ultrasound outcomes. Both mean BSC spectrum-based and mean GLCM-based measures exhibited significant spatial differences across presurgical and 1-month/2-month time points, distal stumps enclosed proximity to the injury site being particularly affected. The two sets of parameters sensitively detected peripheral nerve degeneration at 1-month and 2-month post-injury, with area under the receiver operating charactersitic curve > 0.8 for most parameters. The results also indicated that the many BSC spectrum-based and GLCM-based parameters significantly correlate with each other, and suggested a common structural basis for a diverse set of quantitative ultrasound parameters. The findings of this study suggest that BSC spectrum-based and GLCM-based analysis are promising non-invasive techniques for diagnosing peripheral nerve degeneration.

Purpose: This single-center study aimed to determine whether surgical neurolysis influences muscle power recovery in sciatic nerve palsy following total hip arthroplasty (THA). Methods: Among 1912 THAs performed between 2007 and 2019, a total of 1575 THAs using a posterolateral approach (primary THA, 1483 cases; revision THA, 92 cases) were retrospectively reviewed. Subjects who showed sciatic nerve palsy with motor disturbance were extracted. Demographic data, muscle power, and sensory disturbance at the onset of palsy and at final follow-up were examined. Subjects were divided into two groups (conservative treatment group and surgical treatment group) and clinical outcomes were compared between the two groups. Positive recovery was defined as muscle power greater than Manual Muscle Test grade 3. Results: Thirteen cases (0.8%), including eight in the conservative treatment group and five in the surgical treatment group, showed post-operative sciatic nerve palsy. Four cases (80.0%) in the surgical treatment group achieved full muscle power recovery. All three subjects who received surgical treatment on the day of onset of palsy achieved full muscle power and sensory recovery. More patients recovered muscle power in the surgical treatment group than in the conservative treatment group. Conclusion: Muscle power recovery was found in 80.0% of cases in the surgical treatment group and 12.5% of the conservative treatment group. All cases that received surgical intervention on the onset day of palsy achieved full muscle power and sensory recovery, whereas no cases achieved full muscle power recovery in the conservative treatment group. Immediate surgical intervention should be considered for sciatic nerve palsy following THA using a posterolateral approach.

Abstract Background Magnetic resonance neurography (MRN) is increasingly used as a diagnostic tool for peripheral neuropathies. Quantitative measures enhance MRN interpretation but require nerve segmentation which is time-consuming and error-prone and has not become clinical routine. In this study, we applied neural networks for the automated segmentation of peripheral nerves. Methods A neural segmentation network was trained to segment the sciatic nerve and its proximal branches on the MRN scans of the right and left upper leg of 35 healthy individuals, resulting in 70 training examples, via 5-fold cross-validation (CV). The model performance was evaluated on an independent test set of one-sided MRN scans of 60 healthy individuals. Results Mean Dice similarity coefficient (DSC) in CV was 0.892 (95% confidence interval [CI]: 0.888–0.897) with a mean Jaccard index (JI) of 0.806 (95% CI: 0.799–0.814) and mean Hausdorff distance (HD) of 2.146 (95% CI: 2.184–2.208). For the independent test set, DSC and JI were lower while HD was higher, with a mean DSC of 0.789 (95% CI: 0.760–0.815), mean JI of 0.672 (95% CI: 0.642–0.699), and mean HD of 2.118 (95% CI: 2.047–2.190). Conclusion The deep learning-based segmentation model showed a good performance for the task of nerve segmentation. Future work will focus on extending training data and including individuals with peripheral neuropathies in training to enable advanced peripheral nerve disease characterization. Relevance statement The results will serve as a baseline to build upon while developing an automated quantitative MRN feature analysis framework for application in routine reading of MRN examinations. Key Points Quantitative measures enhance MRN interpretation, requiring complex and challenging nerve segmentation. We present a deep learning-based segmentation model with good performance. Our results may serve as a baseline for clinical automated quantitative MRN segmentation. Graphical Abstract

Background and Aims: Ultrasound-guided sacral plexus block has been used for anaesthesia and analgesia in lower limb surgeries. This study aimed to compare the block performance characteristics after ultrasound-guided (USG) sacral plexus nerve block (SNB) using the parasacral parallel shift (PSPS) approach versus the classical approach in patients undergoing orthopaedic below-knee limb surgeries. Methods: In this randomised study, 144 adult patients were randomised to receive USG SNB either by the classical approach (Group C) or the PSPS approach (Group P). A fixed dose of 20 ml of 0.5% ropivacaine was administered. Patients also received USG femoral nerve block with 10 ml of 0.5% ropivacaine. The primary outcome was the scanning time between the two groups. Secondary outcomes were the needling time, sensory and motor block onset and postoperative analgesic characteristics between the two groups. A P value of

Cerclage wiring may be used to optimize the stability of intramedullary nail or plate fixations in comminuted proximal femoral fractures, periprosthetic fractures, and other selected cases. In this article, we presented a novel case of iatrogenic sciatic nerve entrapment from cerclage wiring used to supplement intramedullary nail fixation. We also illustrate and highlight the role of ultrasound in assessing the sciatic nerve to make a timely diagnosis.

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]

Piriformis syndrome (PS) is a neuromuscular condition caused by the entrapment of the sciatic nerve at the level of the piriformis muscle (PM) and can cause significant discomfort and disability.PS is often misdiagnosed due to its overlapping symptoms with other lumbar and sciatic issues, and, as such, diagnosing PS remains challenging despite recent invasive and non-invasive diagnostic methods. Diagnostic musculoskeletal ultrasound (MSK US) offers a non-invasive, cost-effective alternative for the identification and evaluation of PS, providing dynamic, realtime imaging of the PM and adjacent structures. This article reviews the applications, advantages, and procedural insights of MSK US in the diagnosis of PS, emphasizing its relevance in rehabilitation settings. We discuss the technical aspects of ultrasound use, interpretation of findings, and integration into clinical practice, aiming to enhance the diagnostic accuracy and therapeutic outcomes for patients with suspected PS. [ABSTRACT FROM AUTHOR]

Objective: This study examines the correlation between MRI findings and difficult dissection during proximal primary hamstring repair and postoperative sciatica. Materials and methods: A total of 32 cases of surgically repaired hamstring tendon tears that underwent preoperative and postoperative MRI were divided into sciatica (n = 12) and control (n = 20) groups based on the presence or absence of postoperative sciatica. Cases were scored by two blinded musculoskeletal radiologists for imaging features associated with difficult surgical dissection and the development of subsequent sciatica. Intra- and interrater agreements, as well as correlation of MRI findings with symptoms (odds ratio, OR), were calculated. Results: On preoperative MRI, diffuse hamstring muscle edema pattern suggestive of active denervation (OR 9.4–13.6), and greater sciatic perineural scar circumference (OR 1.9–2) and length (OR 1.2–1.3) were significantly correlated with both difficult dissection and postoperative sciatica. Preoperatively, a greater number of tendons torn (OR 3.3), greater tear cross-sectional area (CSA, OR 1.03), and increased nerve T2-weighted signal (OR 3.2) and greater perineural scar thickness (OR 1.7) were also associated with difficult dissection, but not postoperative sciatica. On postoperative MRI, hamstring denervation, sciatic nerve tethering to the hamstring tendon, and development of perineural scar and greater perineural scar extent were all significantly correlated with postoperative sciatica. Conclusion: Preoperative hamstring MRI demonstrates findings predictive of difficult sciatic nerve dissection; careful MRI evaluation of the nerve and for the presence and extent of perineural scar is important for preoperative planning. Preoperative and postoperative MRI both depict findings that correlate with postoperative sciatica. [ABSTRACT FROM AUTHOR]

Objectives: Bupropion is an atypical antidepressant that shows robust efficacy in the regulation of neuropathic pain. Citicoline is a dietary supplement which is used as a neuroprotective agent for central nervous system (CNS) disorders. The probable interaction between bupropion and citicoline on neuropathic pain was assessed in male mice. Methods: Neuropathic pain was induced by sciatic nerve ligation. Neuropathic pain was examined in nerve-ligated mice using tail-flick and hot-plate tests. Results: The results indicated that intraperitoneal (i.p.) administration of citicoline (50 and 100 mg/kg) induced an anti-nociceptive effect in nerve-ligated animals. Similarly, i.p. injection of bupropion (2.5 and 5 mg/kg) induced anti-nociceptive effects in nerve-ligated mice. Co-administration of different doses of bupropion (2.5 and 5 mg/kg) along with a low dose of citicoline (25 mg/kg) caused an anti-nociceptive effect by enhancement of tail-flick and hot plate latencies. Interestingly, there is an additive effect between bupropion and citicoline upon the induction of the anti-nociceptive effect. Conclusions: Based on these results, it can be concluded that there is an interaction between bupropion and citicoline upon induction of an anti-nociceptive effect in nerve-ligated mice. [ABSTRACT FROM AUTHOR]

Purpose: Although sciatic nerve (SN) injury is relatively rare, it is a devastating complication after primary and revision total hip arthroplasty (THA). Therefore, precise localization of the SN is essential for arthroplasty surgeons. Methods: We dissected 50 hemipelves from formalin-fixed cadavers. The course and location of the sciatic nerve were investigated in relation to different approaches for THA with the help of anatomical landmarks like the greater trochanter (GT), the iliac tubercle, the ischial tuberosity (IschT), the infrapiriform foramen, and the suprapiriform foramen. Results: We found and exposed the sciatic nerve in all 50 specimens with no sex-specific differences. No SN was encountered up to 22 mm posterior from the GT. The zone affording the highest probability of finding the nerve was posterior to the GT between 32 and 55 mm in 39 (78%) cases, thus defining a danger zone for different approaches for the THA. Conclusion: Special care should be taken with posterior and deep instrument placement between the GT and IschT during THA. Moreover, manipulations in the proximal third of the posterior approach reaching deep and posteriorly should be performed with the utmost care. [ABSTRACT FROM AUTHOR]

Cerclage wiring may be used to optimize the stability of intramedullary nail or plate fixations in comminuted proximal femoral fractures, periprosthetic fractures, and other selected cases. In this article, we presented a novel case of iatrogenic sciatic nerve entrapment from cerclage wiring used to supplement intramedullary nail fixation. We also illustrate and highlight the role of ultrasound in assessing the sciatic nerve to make a timely diagnosis. [ABSTRACT FROM AUTHOR]

Chronic pain due to peripheral neuropathy can lead to sleep disorders that significantly worsen the patient's quality of life. Previously, we conducted brain wave measurements in a rat model of neuropathic pain and identified its potential as a model for sleep disorders associated with chronic pain (reported). In this study, we quantified melatonin secretion and assessed its circadian rhythm in a rat model of pain-induced sleep disorder. To create a model of chronic constriction injury (CCI), rats were loosely tied around the sciatic nerve, with approximately 1 mm spacing, 14 days before the experiment. Rats with no ties around the sciatic nerve were used as controls. Electroencephalograms and electromyograms were recorded for 3 days, and the episodes of waking, REM sleep, and non-REM sleep were compared between the groups. The samples for microanalysis were collected every 30 min and used for melatonin analysis. Compared to the control group, the CCI model group exhibited an increase in wake episodes and a decrease in non-REM sleep episodes. Analysis of the area under the curve of melatonin secretion revealed a significant increase in melatonin secretion and a loss of circadian rhythm in the CCI model group. Melatonin secretion markedly increased accompanied by loss of circadian rhythm in a rat model of CCI. Further studies investigating the causal relationship between neuropathic pain and melatonin secretion are warranted. [ABSTRACT FROM AUTHOR]

Introduction World literature data indicate the effectiveness of single intraoperative electrical stimulation (IES) of the proximal segment of the damaged nerve to stimulate its regeneration, but there is no data on its effect on the long-term results of autoplasty of resection defects. The purpose of the work was to evaluate the long-term results of a single IES after autologous plastic surgery of the tibial portion of the sciatic nerve in rats. Materials and methods Thirty rats after autologous repair of the resection defect of the tibial portion of the sciatic nerve were divided into series 1 (unstimulated control, n = 16) and series 2 (single IES for 40 minutes, n = 14). At 4 and 6 months after surgery, the static sciatic functional index (SFI) and morphometry of epoxy transverse semithin sections of the tibial nerve at the level of the middle third of the leg were assessed. For comparison with the normal values, the corresponding data from 7 intact rats were used. Results The number of animals with excellent results of SFI restoration was 12.5 % in series 1 and 50 % in series 2 (p = 0.05). The numerical density of regenerated myelinated fibers (MF) exceeded the norm: in series 1 — by 63 % (p < 0.01) and 34 % (p < 0.01), in series 2 — by 58 % (p < 0.01) and 47 % (p < 0.01), respectively. In series 2, there were greater values in comparison with series 1: the median diameters of MFs were by 11.7 % and 15.7 %, the median diameters of their axons were by 5.4 % and 11.9 %, the median thickness of the myelin sheath was by 17.0 % and 24.1 %, respectively (p < 0.05 4 months and p < 0.01 6 months after surgery). Four months after surgery in series 1 and 2, the numerical densities of endoneurial vessels exceeded the intact control by 134 % (p < 0.05) and 156 % ( 0.05), their average diameters by 18 % and 16 % (p < 0.01) respectively, and lumen diameters increased only in series 2 by 8 % (p = 0.07). After 6 months of the experiment in series 1 and 2, the numerical densities of microvessels decreased, but significantly exceeded the control by 66 % (p < 0.05) and 83 % (p < 0.05), the average diameters — by 14 % and 36 % (p < 0.05), lumen diameters — by 26 % (p < 0.05) and 50 % (p < 0.01), respectively. Discussion The difference between stimulated and unstimulated animals in all MF size parameters 6 months after surgery was greater than after 4 months, indicating a persistent neuroregenerative effect. Conclusions A significant increase in the diameters of regenerating nerve fibers in the tibial nerve, as well as the diameters of their axons and the thickness of the myelinated sheaths 4 and 6 months after autoplasty of the tibial portion of the sciatic nerve in the group of animals with a single 40-minute IES of the proximal portion of the sciatic nerve indicates the promoting effect of the applied additive effect on regenerative axono- and myelinogenesis. Increase in the lumens and improvement of blood flow of the endoneurial vessels of the tibial nerve in the series with IES ensured the stability of the neuroregenerative effect. The functional significance of the effects of a single IES is confirmed by a significantly higher percentage of animals with excellent results in restoring the static functional index.

Objective(s): Despite the many benefits of mesenchymal stem cell (MSC) transplantation for tissue regeneration, there are some limitations to using them, including the high costs, applying invasive procedures, the possibility of transplant rejection, and cell malignancy. This study aimed to investigate the effect of secretions of bone marrow stromal cells (BMSCs) with the cell-free strategy on damaged sciatic nerve with an emphasis on the role of apoptosis and the expression of myelin protein zero (MPZ) and nerve growth factor (NGF) proteins.Materials and Methods: BMSCs were cultured and a 25-fold concentrated conditioned medium (CM) from the cells was provided. After creating a crush injury in the left sciatic nerve of male rats, BMSCs or CM were injected into the injured site of the nerve. Four weeks later, the expression of MPZ, NGF, Bax, and Bcl-2 proteins in the sciatic nerve and histological parameters of the sciatic nerve and gastrocnemius muscle were assessed.Results: The results demonstrated that injection of CM decreased apoptosis and increased expression of MPZ and NGF proteins, improving remyelination and regeneration of the sciatic nerve almost as much as the transplantation of the BMSCs themselves compared to the control group.Conclusion: The results suggest that BMSC secretions may improve remyelination and regeneration of damaged sciatic nerve by increasing the expression of MPZ and NGF and decreasing apoptosis.