Sciatic Research Articles

Nigella sativa oil on chronic constrictive injury (CCI) induced neuropathic pain of sciatic nerve in Wistar rats

Background: Various adverse effects have been reported with conventional treatments of neuropathic pain. Nigella sativa (N. sativa), a medicinal herb, has been shown to possess several beneficiary effects. Objective: To assess the effects of N. sativa oil on neuropathic pain and ATP sensitive potassium channel (KATP) in Wistar rats. Methods: This experimental study was conducted on 120 Wistar rats (200±50gm). On the basis of treatments, all rats were grouped into Group I [normal control (NC) normal saline (NS) 5 ml/kg]; Group II [sham control (SC) {sham surgery + NS}], Group III [CCI control (CCIC) {Chronic constriction injury to sciatic nerve (CCI) + NS}]; Group IV [N. sativa oil experimental (NSOexp) {CCI + N.sativa (400 mg/kg)}], Group V [Glibenclamide experimental (Gliexp) {CCI + N. sativa (400 mg/kg) + glibenclamide (15 mg/kg)}] groups. Both the NSO and NS were administered orally once daily for consecutive 21 days and single dose of glibenclamide was given intraperitoneally on the day of experiment, to the respective rats. Then on the basis of neuropathic pain evaluation tests, all the groups were subdivided into ‘a’ [for sciatic functional index (SFI) in walking track analysis], ‘b’ [for tail flick latency (TFL) in cold tail immersion test], ‘c’ [for paw withdrawal threshold (PWT) in von Frey test], and ‘d’ (for rection time in hot plate test). The statistical analysis was done by one way ANOVA followed by Bonferroni post hoc test. Results: In this study, significantly (pd”0.001) higher SFI, TFL, PWT and reaction time were found in NSO exp rats when compared to those of CCIC rats. In addition, there were significant (pd”0.001) differences in the above-mentioned variables between rats of NSO exp group and Gliexp group. Conclusion: From the present study it might be concluded that, N. sativa prevents worsening of neuropathic pain in Wistar rats by blocking KATP channel. J Bangladesh Soc Physiol 2023;18(1): 35-45

Fabrication of Anatomically Equivalent Pectin-Based Multifilament Nerve Conduits.

Reuniting denuded nerve ends after a long segmental peripheral nerve defect is challenging due to delayed axonal regeneration and incomplete, nonspecific reinnervation, as conventional hollow nerve guides fail to ensure proper fascicular complementation and obstruct axonal guidance across the defects. This study focuses on fabricating multifilament conduits using a plant-derived anionic polysaccharide, pectin, where the abundant availability of carboxylate (COO-) functional groups in pectin facilitates instantaneous sol-gel transition upon interaction with divalent cations. Despite their advantages, pectin hydrogels encounter structural instability under physiological conditions. Hence, pectin is conjugated with light-sensitive methacrylate residues (49.8% methacrylation) to overcome these issues, enabling the fabrication of dual cross-linked multifilament nerve conduits through an ionic interaction-driven, template-free 3D wet writing process, followed by photo-cross-linking at 525 nm. The anatomical equivalence including peri-, epi-, and endoneurium structures of the customized multifilament conduits was confirmed through scanning electron micrographs and micro-CT analysis of rat and goat sciatic nerve tissues. Furthermore, the fabricated multifilament nerve conduits demonstrated cytocompatibility and promoted the expression of neuron-specific intermediate filament protein (NF-200) in PC12 cells and neurite outgrowth of 16.90 ± 1.82 μm on day 14. Micro-CT imaging of an anastomosed native goat sciatic nerve with an 8-filament conduit demonstrated precise fascicular complementation in an ex vivo interpositional goat model. This approach not only eliminates the need for a suture-intensive ligation process but also highlights the customizability of multifilament conduits to meet patient- and injury-specific needs.

Agomelatine-loaded nanostructured lipid carriers alleviate neuropathic pain in rats by Nrf2/HO-1 signalling pathway.

Neuropathic pain arises from impairments or malfunctions within the nervous system, resulting in atypical transmission and interpretation of pain signals. In the present study, we examined the neuroprotective effects of agomelatine (AGM) and agomelatine-loaded nanostructured lipid carriers (AGM-NLCs) in neuropathic animal models induced by chronic constriction injury (CCI) of the sciatic nerve. Male Sprague Dawley rats were divided into seven experimental groups to compare the effects of AGM and AGM-NLCs, which were administered at 20 mg/kg for 14 consecutive days after CCI. Our finding demonstrated that CCI triggered the onset of analgesia in these animals, corroborated by mechanical allodynia and thermal hyperalgesia. Furthermore, CCI induced an elevation in inflammatory mediators such as interleukin (IL)-1β and inducible nitric oxide synthase (iNOS), and downregulated heme oxygenase-1 (HO-1) and nuclear factor E2-related factor (Nrf2). Treatment with AGM and AGM-NLCs reversed inflammatory cascades and elevated antioxidant enzyme levels, leading to a reduction in paw withdrawal latency and threshold in rats. To further investigate the effect of AGM and AGM-NLCs, all-trans retinoic acid (ATRA) was administered, which antagonizes Nrf2. ATRA substantially downregulated Nrf2 expression and exacerbated thermal hyperalgesia, whereas Nrf2 and HO-1 expressions were significantly upregulated after AGM-NLCs administration. Overall, the results demonstrated that AGM-NLCs offer promising antinociceptive and anti-inflammatory properties in alleviating neuropathic pain symptoms, which can be attributed to improved drug delivery and therapeutic outcomes compared with AGM alone.

Peripheral nerve traction injury modeling in an experiment

Background. Peripheral nerve (PN) injuries can lead to significant functional impairment and reduced quality of life. Functional recovery of PN is a complex process dependent on many factors, some of which can be controlled to improve outcomes. The number of wounded people with damage to the peripheral nerves of the limbs can be up to 25 % in war conditions. The degree of disability of patients is 65–70 %, so the issue of restoring peripheral nerves is extremely relevant, especially during wartime. The purpose was to develop a model of PN traction injury in an experiment resulting from longitudinal stretching of the sciatic nerve using a tool modified based on a standard self-retaining retractor, which provides the possibility of reproducing traumatic conditions that most accurately imitate real clinical cases. Materials and methods. The study was conducted on 20 outbreed male rats (average weight of 225 ± 55 g) kept in standard conditions of the vivarium of the State Institution “Romodanov Neurosurgery Institute of the National Academy of Medical Sciences of Ukraine” in compliance with current norms of bioethics. The animals were divided into two groups: the first one (n = 10) — traction injury of the nerve, withdrawal from the experiment after 15 days with further examination of the damaged area with the light and electron microscopy. The second group of animals (n = 10) — traction injury of the nerve, withdrawal from the experiment after 30 days with further examination of the damaged part of the nerve with the help of light and electron microscopy. Before surgery, on the 15th and 30th day after simulating injury (before the nerve harvesting for morphological analysis), the sciatic functional index (SFI) was determined using the walking track test in groups I and II of animals, respectively. Rats were maintained on a standard 12-h light/dark cycle with free access to food and water. The experiment ended by removing the animals from the experiment by injecting a lethal dose of thiopental sodium. For a more detailed analysis, on the 15th and 30th day after the start of the experiment, repeated surgical interventions were performed to collect the appropriate sections of the nerve for morphological examination. For accurate identification of the proximal end of the nerve, the method of applying a ligature to the epineurium was used, which allowed to clearly demarcate the studied areas for further analysis. Structural changes in the nerve tissue were analyzed using light and electron microscopy, which provided high detail of morphological characteristics. Results. At the beginning of the experiment, before traction injury, the SFI in the first group was 2.26 ± 0.27, and in the second group — 3.14 ± 0.53. Fifteen days after injury simulation, the SFI in the first group was 68.90 ± ± 1.61, and in the second group — 70.31 ± 1.75, the difference between the indicators was statistically insignificant (p ≥ 0.05). When comparing the SFI before and after injury, the difference was statistically significant (p < 0.0014 and p < 0.0032, respectively). Thirty days after injury simulation, the SFI in the second group was 32.27 ± 1.13 and, compared to the indicator on the 15th day after the injury, it differed statistically significantly in favor of the indicator after 30 days (p < 0.0026). From the biomechanical point of view, three main types of injuries can be distinguished, when traction is the main traumatic mechanism: elastic stretching, inelastic (plastic) stretching and rupture. Elastic stretching is characterized by the return of the nerve to its original length after removal of traction. With a further increase in the stretching force, the nerve enters the phase of plastic deformation, during which irreversible changes in its structure occur, such as the rupture of axons, endoneural and perineural sheaths. When a certain threshold of stretching is exceeded (in particular, when the hook was moved along racks at position of 9, 10, 11 teeth), nerve rupture occurred. The results of morphological studies are planned to be described in detail in future scientific publications. Conclusions. 1. The model of the peripheral nerve traction injury is objective as evidenced by the sciatic nerve functional index. This technique is easily reproducible and does not require expensive and complex equipment. 2. The use of a model of peripheral nerve traction injury in an experiment, with the aim of studying the therapeutic effects in this type of trauma, will allow to expand the understanding of its patho- and morphogenesis and to improve treatment strategy. 3. Extrapolation of this model to clinical practice will allow to improve the treatment of victims with the consequences of combat injuries to peripheral nerves, where a similar mechanism of trauma often occurs.

Outcomes of sciatic neurolysis in chronic hamstring tears: a retrospective case series.

Proximal hamstring tears may present with neurological dysfunction due to compression or stretching of the sciatic nerve. The purpose of this study was to evaluate the effectiveness of hamstring repair with concurrent sciatic nerve neurolysis for clinical outcomes and patient symptoms. A retrospective chart review of patients who were diagnosed with hamstring injury at a large tertiary care institution was conducted. Patients with chronic tears (> 6weeks from injury to surgery) who underwent hamstring repair were reviewed for demographics, clinical variables including symptoms of sciatic neuritis, sciatic nerve abnormalities on MRI, and postoperative outcomes. Chi-square tests were used for categorical variables, t test for continuous variables. Pairwise t tests were used to compare average pre- and postoperative strength for patients with and without symptoms of sciatic neuritis. Thirty-two patients with chronic hamstring tears were included in the analysis. Patients were 59.4% female with an average age of 51.4years (SD 13.1). Preoperatively, 27 patients (84.4%) were noted to have symptoms of sciatic neuritis. These patients did not differ in age (p = .677) or sex (p = .374) from patients without preoperative symptoms. Sciatic nerve abnormalities were noted on MRI report in 7 patients who had sciatic nerve symptoms and 0 patients who did not have sciatic nerve symptoms. Symptomatic improvement was seen in 21/26 (81%) of patients who had preoperative neurological symptoms, and in 6/7 (86%) of patients with MRI findings. All patients had equivalent or improved strength postoperatively. A sciatic nerve neurolysis is a safe and effective procedure to perform on patients with preoperative sciatic nerve symptoms and chronic hamstring tears that leads to improvement in neurological symptoms and strength. In neurologically asymptomatic patients with chronic hamstring injuries and MRI findings indicating possible nerve damage, a discussion should be held about the risks and benefits of performing a sciatic nerve neurolysis.

Electroacupuncture alleviates sciatic nerve injury and inhibits autophagy in rats.

Sciatic nerve injury is a common form of peripheral nerve injury (PNI). It has been suggested that electroacupuncture (EA) stimulation at GB30 and ST36 can improve nerve dysfunction post-PNI. Autophagy is an important factor in the regeneration of sciatic nerves and recovery of motor function. Therefore, we investigated the biological effects of EA and examined whether these were mediated by autophagy in sciatic nerve injury. Mechanical clamping of the sciatic nerve in Sprague-Dawley rats was performed to establish an experimental model of sciatic nerve injury. EA stimulation was administered once daily for 15 min for seven consecutive days beginning 1 week after successful modeling. The recovery of sciatic nerve function was examined via the sciatic functional index (SFI) test. Morphometric analysis was conducted by staining nerve samples with toluidine blue. Autophagy-associated protein levels were measured via Western blotting. EA stimulation at GB30 and ST36 significantly increased the number of myelinated fibers, axonal and fiber diameters, and the thickness of the myelin sheath in our rat model of sciatic nerve injury. In addition, EA stimulation greatly facilitated nerve regeneration following sciatic nerve injury. Moreover, sciatic nerve injury-induced autophagy was inhibited by EA stimulation. EA facilitates recovery of injured sciatic nerves and inhibits autophagy in a rat model.

Coiling of echogenic perineural catheters with integral stylet: A proof-of-concept randomized control trial in a sciatic nerve block simulator and a pilot study in orthopaedic-trauma patients.

Backround/Objectives We investigated a technique that facilitates the coiling of a regular straight catheter (with integral stylet) behind the sciatic nerve in an ultrasound (US) regional anaesthesia simulator, and then applied our findings to a series of orthopedic-trauma patients. Methods We conducted a randomized study of two methods of perineural catheter advancement in a sciatic nerve block Blue Phantom simulator. Two groups of twenty catheters each (method A and method B) were evaluated under real-time ultrasound imaging. The needle in-plane/nerve in-short-axis technique was applied. In method A the catheter was advanced beyond the needle tip with the integral stylet extending along its entire length; in method B the catheter was advanced after its integral stylet was retracted by 6 cm, thus providing flexibility to the catheter’s distal end. Additionally, to assess the procedural effectiveness of method B coiling technique, a pilot study was conducted examining 25 perineural catheters coiled underneath the sciatic nerve in trauma-orthopaedic patients to document any displacement of catheters’ tip from their initial position (for 36 hours postoperatively). Results In the simulation study, method B led to a significantly higher percentage (18/20:90%) of coiled catheters than method A (3/20:15%). Two coiled catheters of method B were found kinked/obstructed. In our patients, after catheter insertion, the distal end of 2/25 (8%) coiled catheters was obstructed. One perineural catheter was dislodged. For the remaining 22 (88%) catheters, ultrasound imaging demonstrated that local anaesthetic infusion made contact with the sciatic nerve, indicating no displacement of the catheter’s distal end postoperatively. Conclusion Regular straight perineural catheters can be easily coiled if their integral stylet is partially retracted. This coiling method offers extra catheter length adjacent to the nerve structure which potentially mitigates catheter tip displacement. Trial registration clinicaltrials.gov, registration No: NCT06568510, 23/08/2024, registration URL: https://clinicaltrials.gov/study/NCT06568510?intr=coiling%20of%20echogenic%20sciatic%20nerve&rank=1#study-overview

Electrospun PCL Nerve Wrap Coated with Graphene Oxide Supports Axonal Growth in a Rat Sciatic Nerve Injury Model.

Background/Objectives: Peripheral nerve injuries (PNIs) are a debilitating problem, resulting in diminished quality of life due to the continued presence of both chronic and acute pain. The current standard of practice for the repair of PNIs larger than 10 mm is the use of autologous nerve grafts. Autologous nerve grafts have limitations that often result in outcomes that are not sufficient to remove motor and sensory impairments. Bio-mimetic nanocomposite scaffolds combined with mesenchymal stem cells (MSCs) represent a promising approach for PNIs. In this study, we investigated the potential of an electrospun wrap of polycaprolactone (PCL) + graphene oxide (GO), with and without xenogeneic human adipose tissue-derived MSCs (hADMSCs) to use as a platform for neural tissue engineering. Methods: We evaluated, in vitro and in vivo, the potential of the nerve wrap in providing support for axonal growth. To establish the rat sciatic nerve defect model, a 10 mm long limiting defect was created in the rat sciatic nerve of 18 Lewis rats. Rats treated with the nanocomposites were compared with autograft-treated defects. Gait, histological, and muscle analyses were performed after sacrifice at 12 weeks post-surgery. Results: Our findings demonstrate that hADMSCs had the potential to transdifferentiate into neural lineage and that the nanocomposite successfully delivered hADMSCs to the injury site. Histologically, we show that the PCL + GO nanocomposite with hADMSCs is comparable to the autologous nerve graft, to support and guide axonal growth. Conclusions: The novel PCL + GO nerve wrap and hADMSCs used in this study provide a foundation on which to build upon and generate future strategies for PNI repair.

Ultrasound of Sciatic Nerve Problems Compared to MRI.

Ultrasound of Sciatic Nerve Problems Compared to MRI.

Magnetic Separation of Schwann Cells from Mouse Sciatic Nerves

Magnetic Separation of Schwann Cells from Mouse Sciatic Nerves

Magnetic Separation of Schwann Cells from Mouse Sciatic Nerves

Magnetic Separation of Schwann Cells from Mouse Sciatic Nerves

Diosmin and Hesperidin Have a Protective Effect in Diabetic Neuropathy via the FGF21 and Galectin-3 Pathway.

Background and Objectives: This study aimed to investigate the protective effect of diosmin and hesperidin in diabetic neuropathy using a rat model, focusing on their impact on nerve regeneration through the fibroblast growth factor 21 (FGF21) and galectin-3 (gal3) pathway. Materials and Methods: Forty adult male Wistar rats were used in this study. Diabetes was induced using streptozotocin (STZ), and the rats were divided into control, diabetes and saline-treated, diabetes and diosmin + hesperidin (150 mg/kg) treated, and diabetes and diosmin + hesperidin (300 mg/kg) treated groups. Electromyography (EMG) and inclined plane testing were performed to assess nerve function and motor performance. Sciatic nerve sections were examined histopathologically. Plasma levels of FGF21, galectin-3, and malondialdehyde (MDA) were measured as markers of oxidative stress and inflammation. Results: Diabetic rats treated with saline displayed reduced nerve conduction parameters and impaired motor performance compared to controls. Treatment with diosmin and hesperidin significantly improved compound muscle action potential (CMAP) amplitude, distal latency, and motor performance in a dose-dependent manner. Histopathological examination revealed decreased perineural thickness in treated groups. Additionally, treatment with diosmin and hesperidin resulted in increased plasma FGF21 levels and reduced plasma levels of galectin-3 and MDA, indicating decreased oxidative stress and inflammation. Conclusions: Diosmin and hesperidin exhibited protective effects in diabetic neuropathy by promoting nerve regeneration, enhancing nerve conduction, and improving motor performance. These effects were associated with modulation of the FGF21 and galectin-3 pathway. These findings suggest that diosmin and hesperidin may hold potential as adjunctive therapies for diabetic neuropathy.

Harmaline attenuates chemotherapy-induced peripheral neuropathy: Modulation of Nrf-2 pathway and NK-1 receptor signaling

Peripheral neuropathy, resulting from damage to peripheral nerves, manifests as weakness, numbness, and pain, primarily affecting extremities and significantly impairing quality of life, especially in the elderly. Current treatments often entail severe side effects, necessitating the exploration of alternative therapies. Harmaline, a β-carboline alkaloid derived from Peganum harmala, exhibits promising antioxidant and anti-inflammatory properties. This study aimed to assess the efficacy of harmaline in a vincristine-induced mouse model of peripheral neuropathy. Swiss albino mice received vincristine (0.1 mg/kg, i.p.) for 10 days to induce neuropathy. Harmaline (5 and 10 mg/kg, i.p.) was administered 30 min before vincristine and continued until day 14 to evaluate its protective effects. Behavioral assessments were conducted on days 7 and 14. Vincristine treatment significantly heightened sensitivity to cold, measured by cold plate and acetone drop tests, and to heat, assessed via the hot plate test, while also impairing motor coordination. Biochemical analyses revealed decreased levels of GSH and Nrf-2, alongside elevated TBARS and IL-1β levels in sciatic nerve tissue. Harmaline administration markedly alleviated both behavioral and biochemical alterations induced by vincristine, with the 10 mg/kg dose exhibiting the most pronounced effects. Notably, harmaline treatment elevated GSH and Nrf-2 levels while reducing TBARS and IL-1β. Furthermore, substance-P treatment reversed the protective effects of harmaline, implicating the NK-1 receptor in its mechanism of action. In conclusion, harmaline demonstrates significant potential in mitigating vincristine-induced peripheral neuropathy by reducing oxidative stress through Nrf-2 activation and lowering IL-1β levels, likely via NK-1 receptor inhibition.

Artichoke leaf hydroethanolic extract reduces neuropathic pain in a rat model of chronic constriction injury via attenuating the sciatic nerve oxidative stress

Neuropathic pain, a nerve damage consequence, presents symptoms such as dysesthesia, hyperalgesia, and allodynia. This study aimed to evaluate the alleviating potential of artichoke leaf extract in neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve in male rats. The hydroethanolic extract of artichoke leaf was administered via gavage at doses of 200, 400, and 800 mg/kg for 21 days. Behavioural tests were conducted on days 1, 4, 7, 14, and 21 post-surgeries. Only the dose of 800 mg/kg significantly reduced thermal hyperalgesia and allodynia from day 14 and mechanical allodynia from day 7, and the other doses did not affect behaviours. Biochemical analysis showed that artichoke extract decreased lipid peroxidation and restored antioxidant enzyme activities (SOD and GPx) in the sciatic nerve tissue. In conclusion, artichoke leaf extract administration diminishes neuropathic pain-related behaviours by enhancing antioxidant capacity and reducing oxidative stress in the rats’ sciatic nerve.

Inhibition of KIF5b-mediated Nav1.8 transport by ropivacaine contributes to axonal regeneration following sciatic nerve injury in rats

Peripheral nerve injury (PNI), typically caused by traumatic accidents or medical events, is currently one of the most common diseases that leads to limb disability. After PNI, tetrodotoxin-resistant voltage-gated sodium channel Nav1.8 is upregulated at the lesion site. Our earlier study suggested that ropivacaine promotes axon regrowth by regulating Nav1.8-mediated macrophage signaling. Nevertheless, the mechanism of ropivacaine in regulation of Nav1.8 expression remains incompletely understood. Kinesin family 5b (KIF5b) was reported to mediate the Nav1.8 axonal transport from dorsal root ganglia (DRGs) to lesion site. Herein, we investigated whether ropivacaine promotes axon regeneration through inhibition of KIF5b-mediated Nav1.8 transport. Reduced levels of KIF5b and Nav1.8 in DRGs coincide with their increase at the lesion site. Nav1.8 mRNA was significantly increased at the lesion site but not in DRGs. Surprisingly, ropivacaine reversed the alterations of Nav1.8 and KIF5b protein expression without affecting Nav1.8 mRNA level. Due to KIF5b overexpression in DRGs, Nav1.8 protein level was significantly decreased in DRGs and increased at the lesion site. We also found KIF5b overexpression significantly impaired behavioral functions, reduced the recovery index of compound muscle action potential (CMAP) amplitude, inhibited axonal regrowth, slowed M1 macrophage infiltration and shift to M2 phenotype, and delayed myelin debris clearance. Notably, all aforementioned results caused by KIF5b overexpression were alleviated by ropivacaine. Furthermore, we demonstrated that inhibition of Nav1.8 transport by A-803467 produced mitigating effects on the impairment of regenerative capacity induced by KIF5b overexpression similar to ropivacaine. These results suggest that ropivacaine promotes axonal regeneration at least partially by inhibiting KIF5b-mediated Nav1.8 forward transport.

Peripheral Nerve Injury After Deoxycholic Acid (ATX-101) Injection in an Experimental Rat Model.

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. This study seeks to characterize the nerve injection injury from ATX-101 in an experimental rat model. Using a rat sciatic nerve injection model, intrafascicular and extrafascicular injections of deoxycholic acid (ATX-101) were compared to lidocaine (positive control) and saline (negative control). Nerves were harvested at a 2-week endpoint for histomorphometric analysis. Cross-sectional area of nerve injury was significantly increased by ATX-101 injection at 75±15% with intrafascicular ATX-101 (p<0.001), 41±21% with extrafascicular ATX-101 (p<0.01), and 38±20% with positive control lidocaine (p<0.01) compared to 7±13% with negative control saline. Demyelinating injury was a significant mechanism of injury in the affected nerve fibers compared to uninjured nerve fibers (p<0.04), but there was no difference in axon-to-myelin area ratio between the lidocaine and ATX-101 cohorts. After two weeks, Wallerian degeneration was evident with only small regenerating nerve fibers present in the ATX-101-injured groups compared to saline (2.54±0.26um vs 5.03±0.44um, p<0.001) in average width. Deoxycholic acid (ATX-101) is capable of 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 providing ATX-101 injections.

A method for quantitative spatial analysis of immunolabeled fibers at regenerative electrode interfaces

BackgroundRegenerative electrodes are being explored as robust peripheral nerve interfaces for neuro-prosthetic control and sensory feedback. Current designs differ in electrode number, spatial arrangement, and porosity which impacts the regeneration, activation, and spatial distribution of fibers at the device interface. Knowledge of sensory and motor fiber distributions are important in optimizing selective fiber activation and recording. New MethodWe use confocal microscopy and immunofluorescence methods to conduct spatial analysis of immunolabeled fibers across whole nerve cross sections. ResultsThis protocol was implemented to characterize motor fiber distribution within 3 macro-sieve electrode regenerated (MSE), 3 silicone-conduit regenerated, and 3 unmanipulated control rodent sciatic nerves. Total motor fiber counts were 1485 [SD: +/- 50.11], 1899 [SD: +/- 359], and 5732 [SD: +/- 1410] for control, MSE, and conduit nerves respectively. MSE motor fiber distributions exhibited evidence of deviation from complete spatial randomness and evidence of dispersion and clustering tendencies at varying scales. Notably, MSE motor fibers exhibited clustering within the central portion of the cross section, whereas conduit regenerated motor fibers exhibited clustering along the periphery. Comparison with Existing MethodsPrior exploration of fiber distributions at regenerative interfaces was limited to either quadrant-based density analysis of randomly sampled subregions or qualitative description. This method extends existing sample preparation and microscopy techniques to quantitatively assess immunolabeled fiber distributions within whole nerve cross-sections. ConclusionsThis approach is an effective way to examine the spatial organization of fiber subsets at regenerative electrode interfaces, enabling robust assessment of fiber distributions relative to electrode arrangement.

Блокада нервов нижней конечности: показания и преимущества

An inadequate approach to the choice of anesthetic care during surgery and in the postoperative period leads to numerous complications, chronic pain, decreased quality of life, as well as to the formation of a negative patient attitude and dissatisfaction with anesthetic care. Currently, there is a constant search for optimal methods of anesthetic management, especially in high-risk patients. Objective. To summarize and present current information on lower limb nerve blockade. Materials and methods. During the research work, an analysis of dissertations on this topic for 2014–2023 was carried out, and Internet resources Elibrary, Cyberleninka, PubMed for the last 9 years were used, since there are not enough literary sources on this topic from 2018 to 2023. Results. An analysis of Russian and foreign literature for 2014–2023 was given, devoted to such a type of anesthetic management as lower limb nerve blockade. Indications, anatomical features, methods, complications in femoral, obturator and sciatic nerve blockades are described. Conclusion. Due to the use of ultrasound navigation, neuromuscular stimulation, catheter technologies, it has become possible to perform peripheral blockades with a minimal risk of complications, as well as to carry out extended peripheral blockades, which allows to speed up the postoperative recovery of patients. Due to the lack of influence of peripheral blockades on hemodynamics, a smaller number of severe complications inherent in central blockades, anesthesiologists increasingly prefer peripheral blockades when choosing a method of anesthetic support for operations on the lower extremities. This type of anesthesia is offered as an alternative to neuraxial blockades, especially in elderly patients with a high class of physical condition.

FGF21 inhibits ferroptosis caused by mitochondrial damage to promote the repair of peripheral nerve injury.

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. 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. 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. 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.

MFG-E8 Ameliorates Nerve Injury-Induced Neuropathic Pain by Regulating Microglial Polarization and Neuroinflammation via Integrin β3/SOCS3/STAT3 Pathway in Mice.

Spinal microglial polarization plays a crucial role in the pathological processes of neuropathic pain following peripheral nerve injury. Accumulating evidence suggests that milk fat globule epidermal growth factor-8 (MFG-E8) exhibits anti-inflammatory effect and regulates microglial polarization through the integrin β3 receptor. However, the impact of MFG-E8 on microglial polarization in the context of neuropathic pain has not yet been investigated. In this study, we evaluated the effect of MFG-E8 on pain hypersensitivity and spinal microglial polarization following spared nerve injury (SNI) of the sciatic nerve in mice. We determined the molecular mechanisms underlying the effects of MFG-E8 on pain hypersensitivity and spinal microglial polarization using pain behavior assessment, western blot (WB) analysis, immunofluorescence (IF) staining, quantitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), and small interfering RNA (siRNA) transfection. Our findings indicate that SNI significantly increased the levels of MFG-E8 and integrin β3 expressed in microglia within the spinal cord of mice. Additionally, we observed that intrathecal injection of recombinant human MFG-E8 (rhMFG-E8) alleviated SNI induced-mechanical allodynia and thermal hyperalgesia. Furthermore, the results suggested that rhMFG-E8 facilitated M2 microglial polarization and ameliorated neuroinflammation via integrin β3/SOCS3/STAT3 pathway in the spinal cord of mice with SNI. Importantly, these effects were negated by integrin β3 siRNA, or SOCS3 siRNA. These results demonstrate that MFG-E8 ameliorates peripheral nerve injury induced-mechanical allodynia and thermal hyperalgesia by driving M2 microglial polarization and mitigating neuroinflammation mediated by integrin β3/SOCS3/STAT3 pathway in the spinal cord of mice. MFG-E8 may serve as a promising target for the treatment of neuropathic pain.