Sciatic Research Articles

Innovative spiral nerve conduits: Addressing nutrient transport and cellular activity for critical-sized nerve defects

Large-gap nerve defects require nerve guide conduits (NGCs) for complete regeneration and muscle innervation. Many NGCs have been developed using various scaffold designs and tissue engineering strategies to promote axon regeneration. Still, most are tubular with inadequate pore sizes and lack surface cues for nutrient transport, cell attachment, and tissue infiltration. This study developed a porous spiral NGC to address these issues using a 3D-printed thermoplastic polyurethane (TPU) fiber lattice. The lattice was functionalized with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) electrospun aligned (aPHBV) and randomly (rPHBV) oriented nanofibers to enhance cellular activity. TPU lattices were made with 25 %, 35 %, and 50 % infill densities to create scaffolds with varied mechanical compliance. The fabricated TPU/PHBV spiral conduits had significantly higher surface areas (25 % TPU/PHBV: 698.97 mm2, 35 % TPU/PHBV: 500.06 mm2, 50 % TPU/PHBV: 327.61 mm2) compared to commercially available nerve conduits like Neurolac™ (205.26 mm2). Aligned PHBV nanofibers showed excellent Schwann cell (RSC96) adhesion, proliferation, and neurogenic gene expression for all infill densities. Spiral TPU/PHBV conduits with 25 % and 35 % infill densities exhibited Young's modulus values comparable to Neurotube® and ultimate tensile strength like acellular cadaveric human nerves. A 10 mm sciatic nerve defect in Wistar rats treated with TPU/aPHBV NGCs demonstrated muscle innervation and axon healing comparable to autografts over 4 months, as evaluated by gait analysis, functional recovery, and histology. The TPU/PHBV NGC developed in this study shows promise as a treatment for large-gap nerve defects.

Effect of Chronic Consumption of Fluoridated Water on Sciatic Nerve Conduction Velocity in Male Wistar Rats.

The long-term effect of fluoridated water consumption during development on the velocity of nerve impulse conduction in the sciatic nerve of rats was assessed. Thirty male Wistar rats, 21 days old, were randomly assigned to five groups. Three groups were given fluoridated water ad libitum (as the only source) at different concentrations (10, 100, and 150 ppm), designated as groups F10, F100, and F150, respectively. The study included a control group (C) that received fluoridated water at the maximum level established by the World Health Organization (1.5 ppm of fluorides) and another group that received deionized water (DW). The animals were treated until they reached 90 days of age. Electrophysiological recordings were performed on the rats' sciatic nerves to determine nerve conduction velocity, and blood plasma was extracted for fluoride concentration analysis. The study found that the F150 group had a lower nerve impulse conduction velocity in the sciatic nerve compared to the C group (P = 0.0015). Additionally, there was a negative correlation between the concentration of fluorides in plasma and the nerve conduction velocity (r = -0.5132, P = 0.0037). These findings indicate that chronic consumption of high concentrations of fluoride leads to a decrease in nerve conduction velocity. This, in conjunction with potential alterations in the central nervous system, may explain the deficits in learning and memory tests that have been documented in numerous studies evaluating individuals exposed to fluoride consumption. These results provide valuable information for understanding the effects and action mechanisms of fluoride in exposed individuals.

Formulation-dependent differences in paclitaxel distribution to anatomical sites relevant to chemotherapy-induced peripheral neuropathy

IntroductionChemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse event observed in patients receiving paclitaxel, associated with initial pathological changes in the peripheral nervous system, i.e., distal nerves and dorsal root ganglia (DRG). The prevalence of CIPN in patients receiving paclitaxel formulated i) in polyethylated castor oil with ethanol (CreEL-PTX), ii) as albumin-bound (nab-PTX), and iii) in XR17 micelles (micellar-PTX), is unexpectedly varying. We hypothesize that the discrepancy in CIPN prevalence could be governed by differences in the extent of paclitaxel distribution across blood-to-tissue barriers at the CIPN-sites, caused by the specific formulation.MethodsThe recently developed Combinatory Mapping Approach for CIPN was used to determine the unbound tissue-to-plasma concentration ratio Kp,uu,tissue, after a 4-h infusion of 4 mg/kg CreEL-PTX, 4 mg/kg nab-PTX or 1 mg/kg micellar-PTX in male and female Sprague Dawley rats. Kp,uu,tissue was determined in conventional (DRG, sciatic nerve) and non-conventional (brain, spinal cord, skeletal muscle) CIPN-sites.ResultsBased on our data, the Cremophor-free paclitaxel formulations were associated with a higher distribution of paclitaxel to CIPN-sites than CreEL-PTX, e.g., Kp,uu,DRG of 0.70 and 0.60 for nab-PTX and micellar-PTX, respectively, in comparison to 0.27 for CreEL-PTX (p < 0.01). In addition, the fraction of unbound paclitaxel in plasma was on average 1.6-fold higher in nab- and micellar PTX arms and equal to 0.061 and 0.065, respectively, compared to 0.039 for the CreEL-PTX treatment arm (p < 0.0001).DiscussionIn the case of similar unbound paclitaxel concentration in the plasma of patients and assumed species-independent extent of paclitaxel transport across the barriers, nab- and micellar-PTX formulations can lead to higher paclitaxel exposure at CIPN-sites in comparison to CreEL-PTX.

Randomized Clinical Study of Nano-Cerium Oxide and its Efficacy in Sciatic Nerve Regeneration: A Histopathological Evaluation

Background: Peripheral nerve damage is a frequent clinical condition. peripheral nerve injuries are variable, and these injuries are mostly caused by trauma. Blunt trauma has many types, including contusion, laceration, stretching, traction, penetrating and perforating injuries, abnormal sleeping positions, external pressure, internal compression, ischemia. Cerium oxide nanoparticles are used widely in the materials field. Besides their material applications. Objective: this study was examining how cerium oxide nanoparticles impact axonal regeneration of the sciatic nerve in rats. Materials and Methods: 24 adult animals used, weighing average (M±SD: 230 ± 20 g). The animals were separated into two group. The first group (control) was left without treatment, The second group (Nano cerium Oxide) was treated orally with 50 mg of Nano cerium oxide daily for 7 days. Right Sciatic nerve was completely transected in all animals. The result evaluated at 4th, 8th and 12th weeks post-operative. Results: The histopathological results, indicated that the high effective result in the second group, then the control group. The control group has a significant nerve damage and some regenerative signs over time. While there are indications of severe damage particularly at 4 and 8 weeks, then presence of almost normal nerve fibers at 12 weeks suggests partial recovery. Conclusion: Nano Cerium Oxide accelerated the regeneration of the peripheral nerves These findings suggest that this nanoparticle could can be seen as a novel therapy for promoting the regeneration of the nervous system.

A nanofibrous polycaprolactone/collagen neural guidance channel filled with sciatic allogeneic schwann cells and platelet-rich plasma for sciatic nerve repair.

Sciatic nerve damage, a common condition affecting approximately 2.8% of the US population, can lead to significant disability due to impaired nerve signal transmission, resulting in loss of sensation and motor function in the lower extremities. In this study, a neural guidance channel was developed by rolling a nanofibrous scaffold produced via electrospinning. The scaffold's microstructure, biocompatibility, biodegradation rate, porosity, mechanical properties, and hemocompatibility were evaluated. Platelet-rich plasma (PRP) activated with 30,000 allogeneic Schwann cells (SCs) was injected into the lumen of the channels following implantation into a rat model of sciatic nerve injury. Recovery of motor function, sensory function, and muscle re-innervation was assessed using the sciatic function index (SFI), hot plate latency time, and gastrocnemius muscle wet weight loss. Results showed mean hot plate latency times of Autograft: 7.03, PCL/collagen scaffolds loaded with PRP and SCs (PCLCOLPRPSCs): 8.34, polymer-only scaffolds (PCLCOL): 10.66, and untreated animals (Negative Control): 12.00. The mean SFI values at week eight were Autograft: -49.30, PCLCOLPRPSCs: -64.29, PCLCOL: -75.62, and Negative Control: -77.14. The PCLCOLPRPSCs group showed a more negative SFI compared to the Autograft group but performed better than both the PCLCOL and Negative Control groups. These findings suggest that the developed strategy enhanced sensory and functional recovery compared to the negative control and polymer-only scaffold groups.

An organic semiconductor implant for wireless stimulation of rat sciatic nerve

An organic semiconductor implant for wireless stimulation of rat sciatic nerve

Therapeutic potential of omaveloxolone in counteracting muscle atrophy post-denervation: a multi-omics approach

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

Hydrogen sulfide alleviates neural degeneration probably by reducing oxidative stress and aldose reductase expression.

We investigated the potential role of hydrogen sulfide (H2S) as a novel therapy for diabetic peripheral neuropathy in diabetic rats. A single dose of streptozotocin (60 mg/kg) was applied to the rats for the diabetic rat models. Sodium bisulfide (50 μmol/kg/d) was injected intraperitoneally daily for 2 weeks as H2S treatment. Electromyogram, haematoxylin eosin staining, transmission electron microscopy, western blotting and enzyme-linked immunosorbent assay were then performed. H2S treatment did not affect body weights, blood glucose levels or liver function of diabetic rats, while the creatine levels of the H2S-treated diabetic rats decreased compared with the diabetic control rats. H2S treatment for 2 weeks did not affect the sciatic nerve conduction velocity of the diabetic rats. However, H2S treatment relieved neurons loss and cell atrophy of dorsal root ganglion, and axon degeneration of sciatic nerve in diabetic rats. Serum super oxide dismutase (SOD) levels and SOD2 levels in the sciatic nerve of diabetic rats were lower than the non-diabetic rats but were restored after H2S treatment. Serum and sciatic nerve homogenate malondialdehyde and aldose reductase expression were higher in diabetic rats but decreased significantly after H2S treatment. Our study revealed that H2S alleviates neural degeneration in diabetic rats probably by reducing oxidative stress and downregulating aldose reductase expression.

Unraveling the therapeutic potential of Astilbe rivularis Buch.-Ham. ex D. Don in attenuation of diabetic neuropathy in laboratory rats

Ethnopharmacological relevanceAstilbe rivularis Buch.-Ham. ex D. Don is a rare medicinal plant, traditionally employed for treating several disorders. The juice, decoction or powder of the roots, rhizomes, leaves and even the entire plant, are used for managing peptic ulcer, diarrhoea, jaundice, sprains and muscular swellings, bone fracture and dislocation of joints, postpartum bleeding and other menstrual disorders. These conventional medicinal uses make Astilbe rivularis a promising candidate for further research. Aim of the studyThis study was designed to explore the neuroprotective potential of hydroethanolic extract of Astilbe rivularis (ARHE) in diabetic neuropathy (DN) in rats. Materials and methodsGC-MS analysis was used to identify the phytoconstituents present in the plant extract. DN was induced by administration of STZ (55 mg/kg, i.p.), 15 min after NAD (230 mg/kg, i.p.) injection. The rats with fasting blood glucose (FBG) level >250 mg/dl were included in the study. DN was assessed by estimating the level of FBG, lipid profile, and invitro and invivo oxidative stress parameters. Additionally, behavioural parameters like, mechanical hyperalgesia, hot and cold allodynia were estimated to assess diabetic neuropathy. Furthermore, the level of antioxidant enzymes like SOD, GSH, and TBARS in sciatic nerve and inflammatory markers like, TGF-β and IL-6 were measured. ResultsAltogether, 30 phytoconstituents were identified including heptafluorobutyric acid, hexadecanoic acid, and beta-sitosterol depicting antioxidant, antidiabetic, and anticancer properties, respectively. Administration of different doses (100, 200, and 400 mg/kg) of ARHE to diabetic rats attenuated elevated blood glucose level and restored lipid profile, body weight, food and water intake, and antioxidant level. Moreover, elevated level of inflammatory markers like, TGF-β and IL-6 was also found to be attenuated in sciatic nerve. Furthermore, ARHE attenuated the pain response assessed by mechanical hyperalgesia and hot and cold allodynia in diabetic neuropathy rats. ARHE also showed inhibitory activity on ALR enzyme and erythrocyte sorbitol accumulation, and ameliorated oxidative stress. Histopathological study indicated improvement in the architecture of sciatic nerve tissue in diabetic neuropathy rats with the treatment of ARHE. ConclusionsConclusively, hydroethanolic extract of Astilbe rivularis exhibited neuroprotective potential and ameliorated diabetic neuropathy in rats.

The protective effect of rutin on sciatic nerve injury in acrylamide-exposed rats and its mechanisms

Rutin (Rut) is a flavonoid with pharmacological activities such as anti-inflammatory and antioxidant. Acrylamide (ACR) is a toxic substance widely found in human life that can induce neurotoxicity. Some studies have confirmed that neurotoxicity caused by ACR induces myelin damage, which in turn causes neurological dysfunction. Therefore, we established a rutin intervention model to investigate the protective effect of Rut on ACR-induced sciatic nerve injury in rats and its mechanism. The results showed that superoxide dismutase (SOD) activity and glutathione (GSH) content increased and lactate dehydrogenase (LDH) activity decreased in the middle and high dose groups of Rut compared with the ACR group, and the expression of Myelin basic protein (MBP), Extracellular-regulated kinase 1/2(ERK1/2), Phosphorylated extracellular regulated kinase 1/2 (P-ERK1/2), and Nuclear factor E-2-associated factor (Nrf2) was promoted in the Rut-protected group, which suggests that Rutin has a protective effect on ACR-induced sciatic nerve injury and that the mechanism of Rutin's protective effect is related to activation of the ERK1/2 pathway and alleviation of oxidative stress injury.

A finite element model for biomechanical characterization of exvivo peripheral nerve dysfunction during stretch.

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

Activation of PAR1 contributes to ferroptosis of Schwann cells and inhibits regeneration of myelin sheath after sciatic nerve crush injury in rats via Hippo-YAP/ACSL4 pathway.

Peripheral nerve injury (PNI) is characterized by high incidence and sequela rate. Recently, there was increasing evidence that has shown ferroptosis may impede functional recovery. Our objective is to explore the novel mechanism that regulates ferroptosis after PNI. LC-MS/MS proteomics was used to explore the possible differential signals, while PCR array was performed to investigate the differential factors. Besides, we also tried to activate or inhibit the key factors and then observe the level of ferroptosis. Regeneration of myelin sheath was finally examined in vivo via transmission electron microscopy. Proteomics analysis suggested coagulation signal was activated after sciatic nerve crush injury, in which high expression of F2 (encoding thrombin) and F2r (encoding PAR1) were observed. Both thrombin and PAR1-targeted activator TRAP6 can induce ferroptosis in RSC96 cells, which can be rescued by Vorapaxar (PAR1 targeted inhibitor) in vitro. Further PCR array revealed that activation of PAR1 induced ferroptosis in RSC96 cells by increasing expression of YAP and ACSL4. Immunofluorescence of sciatic nerve confirmed that the expression of YAP and ACSL4 were simultaneously reduced after PAR1 inhibition, which may contribute to myelin regeneration after injury in SD rats. Inhibition of PAR1 can relieve ferroptosis after sciatic nerve crush injury in SD rats through Hippo-YAP/ACSL4 pathway, thereby regulating myelin regeneration after injury. In summary, PAR1/Hippo-YAP/ACSL4 pathway may be a promising therapeutic target for promoting functional recovery post-sciatic crush injury.

Return of sensation after epidural or perineural administration of ropivacaine to the femoral and the sciatic nerves in dogs undergoing TPLO - a randomized clinical trial

Return of sensation after epidural or perineural administration of ropivacaine to the femoral and the sciatic nerves in dogs undergoing TPLO - a randomized clinical trial

Return of sensation after perineural injection of ropivacaine, bupivacaine or lidocaine to the femoral and sciatic nerves in dogs: a blinded randomised clinical trial

Return of sensation after perineural injection of ropivacaine, bupivacaine or lidocaine to the femoral and sciatic nerves in dogs: a blinded randomised clinical trial

Clinical effects of two doses of magnesium sulphate as adjuvant to ropivacaine for sciatic and saphenous nerve blocks in dogs undergoing tibial plateau leveling osteotomy

Clinical effects of two doses of magnesium sulphate as adjuvant to ropivacaine for sciatic and saphenous nerve blocks in dogs undergoing tibial plateau leveling osteotomy

Effectiveness of the injectable hyaluronic acid-based microparticles loaded with cannabidiol on rat sciatic nerve injury model

Effectiveness of the injectable hyaluronic acid-based microparticles loaded with cannabidiol on rat sciatic nerve injury model

Ultrasound-guided popliteal sciatic nerve block for surgical anesthesia in wound care patients with ongoing anticoagulant/antiaggregant therapy: A single-center, prospective study.

Ultrasound-guided peripheral nerve blocks may be a good alternative in patients under antithrombotic drugs. We evaluated the efficacy of ultrasound-guided popliteal sciatic nerve block in patients undergoing lower extremity wound debridement of whom antithrombotic drugs could not be stopped. We focused on hemorrhagic complications related to sciatic nerve block. Wound care patients followed by Cardiovascular Surgery Department scheduled for lower extremity wound surgery were included in this prospective observational study. Data was collected between March 2021 and September 2022. All patient were under antithrombotic therapy and discontinuation of anticoagulant drugs were not possible. Single-insertion and multiple-injection sciatic nerve block at popliteal region was applied to all patients under ultrasound guidance. Primary outcome was the rate of hemorrhage. Secondary outcomes were block onset times, block success and postoperative analgesia times. Data of 105 patients was evaluated, 87 were male and 18 were female. Mean patient age was 61.92 ± 10.06, mean patient body mass index was 25.68 ± 6.33. All patients were under 1 or more antithrombotic drugs. Only one minor hematoma was detected by postoperative ultrasonography control in 1 patient. Hemorrhage complication rate was 1 of 105 (% 0.95, 95% CI, 0.00024-0.051). Overall block success rate was 99.05%. Mean block onset time was 16.27 ± 5.69 minutes. Mean postoperative analgesia time was 19.5 ± 11.22 hours. Sciatic nerve block under ultrasound guidance using in-plane technique was safe and provided sufficient surgical anesthesia and postoperative analgesia for lower extremity wound debridement surgery in patients on antithrombotic drugs.

Bioactive ECM-Mimicking Nerve Guidance Conduit for Enhancing Peripheral Nerve Repair

Extensive research efforts are being directed towards identifying alternatives to autografts for the treatment of peripheral nerve injuries (PNIs) with engineered nerve conduits (NGCs) identified as having potential for PNI patients. These NGCs, however, may not fulfill the necessary criteria for a successful transplant, such as sufficient mechanical structural support and functionalization. To address the aforementioned limitations of NGCs, the present investigation explored the development of double cross-linked hydrogels (o-CSMA-E) that integrate the biocompatibility of porcine tendon extracellular matrix (ECM) with the antimicrobial and conductive properties of methacrylated quaternary chitosan. The hydrogels had matrices that could promote the growth of axons and the transmission of neural signals. The hydrogels were subsequently incorporated into a nanofibrous PLLA-ZnO sheath scaffold (ZnO@PLLA) to emulate the natural nerve structure, guiding cell growth and facilitating nerve regeneration. The collaboration of core and sheath materials in ZnO@PLLA/o-CSMA-E nerve guidance conduits resulted in enhanced migration of Schwann cells, formation of myelin sheaths, and improved locomotion performance in rats with sciatic nerve defects when in vivo studies were undertaken. Notably, the in vivo studies demonstrated the similarity between the newly developed engineered NGCs and autologous transplants, with the newly engineered NGCs possessing the potential to promote functional recovery by mimicking the tubular structure and ECM of nerves.

Sciatic Nerve Endometriosis - Surgical Approach and Anatomy

Sciatic Nerve Endometriosis - Surgical Approach and Anatomy

Perioperative analgesia requirements and postoperative motor function following saphenous and sciatic nerve blocks in goats anaesthetised for bilateral stifle surgery

Perioperative analgesia requirements and postoperative motor function following saphenous and sciatic nerve blocks in goats anaesthetised for bilateral stifle surgery