Sciatic Functional Index Research Articles

Effects of electromagnetic therapy on proprioception in a rodent animal model of rheumatoid arthritis

IntroductionThis study aimed primarily to investigate the effect of a PEMF on proprioception in terms of mechanoreceptor number and function and secondarily to assess the gait quality (sciatic function index) and arthritis severity (paw volume and body weight) in adjuvant-induced arthritis (AIA) RA model.MethodsTwenty-eight healthy adult male Wistar rats were randomly divided into 3 groups: (I) RA experimental model treated with a PEMF (10 animals), (II) positive control (10 animals), and (III) negative control (8 animals). Group I was exposed to a PEMF (0.3 mT 1 h/day for 2 weeks), while Groups II and III were placed in the same setup, except that the PEMF was turned off. The proprioceptive function [as tactile response (TR) / hopping response (HR) / forelimb placing test (FPT)], paw volume (PF), and mechanoreceptor numbers were then tested.ResultsThere was a significant preservation of mechanoreceptor numbers and proprioception in group I compared to group II, as follows: the number of Ruffini corpuscles mechanoreceptors (p = 0.007) and TR on days 9 and 14 (p = 0.002, 0.012, respectively) with no significant difference compared to group III. Also, PV decreased significantly in group I relative to group II (p = 0.01) with no significant difference for group III.ConclusionsPEMF significantly preserved proprioception receptors and function and decreased inflammation severity in the AIA-RA model.

Nerve guide conduits promote nerve regeneration under a combination of electrical stimulation and RSCs combined with stem cell differentiation.

Nerve guide conduits (NGCs) offer a promising alternative to traditional tools for regenerating peripheral nerves. The efficacy of nerve regeneration and functional recovery is heavily dependent on the electrical, chemical, and physical properties of NGCs. A bionic melt electrowriting (MEW) NGC loaded with placental derived mesenchymal stem cells (PDMSCs) has been developed. Our study introduces a novel approach by utilizing Schwann cells induced from placental mesenchymal stem cells (PDMSCs), showcasing their potential in enhancing nerve regeneration when integrated with conductive nerve guidance conduits. Schwann cells (SCs) are crucial for nerve regeneration, and while various stem cells, including bone marrow stromal cells (BMSCs), have been investigated as sources of SCs for NGC loading, they are often limited by ethical concerns and restricted availability. PDMSCs, however, offer the advantages of widespread sourcing and unique ability to differentiate into SCs, making them an attractive alternative for NGC applications. This NGC utilizes an electrostatic direct writing technique employing polycaprolactone (PCL) for the sheath and a crimped fiber scaffold made of polypyrrole (PPY) incorporated with PDMSCs for its internal structure. The bionic PC-NGC loaded with PDMSCs exhibits favorable characteristics including permeability, mechanical stability, and electrical conductivity. The PPY component effectively transmits physiological nerve signals, thereby promoting nerve regeneration, while the PDMSCs differentiate into Schwann cells, creating a conducive environment for nerve regeneration. This research innovatively combines PDMSCs, known for their wide availability and SC differentiation potential, with a bionic NGC to enhance the treatment of peripheral nerve injuries (PNIs). In vitro evaluations have confirmed the excellent biocompatibility of the materials used. Animal experiments using a rat model with sciatic nerve injury demonstrated that the PC-NGC significently facilitated peripheral nerve regeneration. This was evidenced by improvements in axonal myelination, increased muscle mass, enhanced sciatic nerve function index, and positive electrophysiological findings. These outcomes are comparable to those achieved through autologous transplantation. Characterized by its layered oriented fibers, the bionic PC-NGC integrates multi-scale and multifunctional biomaterials with PDMSCs to effectively address peripheral nerve injuries (PNIs). The use of this printed NGC stimulates neuronal cell growth, thereby accelerating nerve regeneration. This innovative approach in tissue engineering presents a promising clinical treatment strategy for PNIs.

Sustainable Release Selenium Laden with SiO2 Restoring Peripheral Nerve Injury via Modulating PI3K/AKT Pathway Signaling Pathway.

Inhibiting ROS overproduction is considered a very effective strategy for the treatment of peripheral nerve injuries, and Se has a remarkable antioxidant effect; however, since the difference between the effective concentration of Se and the toxic dose is not large, we synthesized a nanomaterial that can release Se slowly so that it can be used more effectively. Se@SiO2 NPs were synthesized using a mixture of Cu2-x Se nanocrystals, and the mechanism of action of Se@SiO2 NPs was initially explored by performing sequencing, immunofluorescence staining and Western blotting of cellular experiments. The mechanism of action of Se@SiO2 NPs was further determined by performing behavioral assays after animal experiments and by sampling the material for histological staining, immunofluorescence staining, and ELISA. The effects, mechanisms and biocompatibility of Se@SiO2 NPs for peripheral nerve regeneration were determined. Porous Se@SiO2 was successfully synthesized, had good particle properties, and could release Se slowly. CCK-8 experiments revealed that the optimal experimental doses were 100 μM H2O2 and 200 μg/mL Se@SiO2, and RNA-seq revealed that porous Se@SiO2 was associated with cell proliferation, apoptosis, and the PI3K/AKT pathway. WB showed that porous Se@SiO2 could increase the expression of cell proliferation antigens (PCNA and S100) and antiapoptotic proteins (Bcl-2), decrease the expression of proapoptotic proteins (Bax), and increase the expression of antioxidative stress proteins (Nrf2, HO-1, and SOD2). EdU cell proliferation and ROS fluorescence assays showed that porous Se@SiO2 promoted cell proliferation and reduced ROS levels. The therapeutic effect of LY294002 (a PI3K/AKT pathway inhibitor) was decreased significantly and its effect was lost when it was added simultaneously with porous Se@SiO2. Animal experiments revealed that the regenerated nerve fiber density, myelin thickness, axon area, gastrocnemius muscle wet-to-weight ratio, myofiber area, sciatic nerve function index (SFI), CMAP, apoptotic cell ratio, and levels of antioxidative stress proteins and anti-inflammatory factors were increased following the administration of porous Se@SiO2. The levels of oxidative stress proteins and anti-inflammatory factors were significantly greater in the Se@SiO2 group than in the PNI group, and the effect of LY294002 was decreased significantly and was lost when it was added simultaneously with porous Se@SiO2. Se@SiO2 NPs are promising, economical and effective Se-releasing nanomaterials that can effectively reduce ROS production, inhibit apoptosis and promote cell proliferation after nerve injury via the PI3K/AKT pathway, ultimately accelerating nerve regeneration. These findings could be used to design new, promising drugs for the treatment of peripheral nerve injury.

The Pulsed Nd:YAG Laser Therapy Enhanced Nerve Regeneration via Apoptosis Inhibition in a Rat Crushed Sciatic Nerve Model.

The study was aimed to validate the efficacy of the pulsed Nd:YAG laser on nerve regeneration in a rat sciatic nerve crushed model. 54 Wistar rats were randomly assigned into three groups: shame control, crush control, and laser treated group. For the laser treated group, the pulsed Nd:YAG laser (10Hz) with 350mJ per pulse in energy density and 50J/cm2 in fluence was applied extracorporeally at the lesion site for 12min to daily deliver 500J immediately and consecutive 9days following the crush injury. At week 1, the apoptosis-related activities in the injured nerve were examined (n = 8/each group). The sciatic functional index (SFI) was measured preoperatively and weekly until 4weeks after the index procedure. The injured nerve and the innervated gastrocnemius muscle histology were assessed at week 4 (n = 10/each group). At week 1, the laser group showed the significant less TUNEL-positive ratio (P < 0.05), and the lower expression of cleaved caspase3/procaspase-3 and beclin-2/beclin-2-associated protein X ratios compared with the crush control. Furthermore, the laser group revealed significantly better SFI since week 1 and throughout the study (P < 0.05, all) compared with the crush control. At week 4, the laser group showed significantly higher axon density, lower myelin g-ratio, and the corresponding higher glycogen expression (P < 0.05, all) in the gastrocnemius muscle compared with those in the crush control. The pulsed Nd:YAG might enhance the injured nerve regeneration via apoptosis inhibition.

Tinospora cordifolia ameliorates paclitaxel-induced neuropathic pain in albino rats

Ethnopharmacological relevanceTinospora cordifolia (T. cordifolia) (Willd.) Miers, a member of the Menispermaceae, family documented in the ancient textbooks of the Ayurveda System of Medicine, has been used in the management of sciatica pain and diabetic neuropathy. AimThe study has been designed to evaluate the antinociceptive potential of various extracts of T. cordifolia stem in Paclitaxel (PT)-generated neuropathic pain model in albino rats and explore its possible mechanism employing molecular docking studies. MethodsStems of T. cordifolia were shade dried, grinded in fine powder, and extracted separately with different solvents viz. ethanol, water & hydro-alcoholic and characterized using LCMS/MS. The antinociceptive property of T. cordifolia stem (200 and 400 mg/kg) was examined in albino rats using a PT-induced neuropathic pain model. Further, the effect of these extracts was also observed using different behavioral assays viz. cold allodynia, mechanical hyperalgesia (pin-prick test), locomotor activity test, walking track test, and Sciatic Functional Index (SFI) in rats. Tissue lysate of the sciatic nerve was used to determine various biochemical markers such as GSH, SOD, TBARS, tissue protein, and nitrite. Further to explore the possible mechanism of action, the most abundant and therapeutically active compounds available in aqueous extract were analyzed for binding affinity towards soluble epoxide hydrolase (sEH) enzyme (PDB ID: 3wk4) employing molecular docking studies. ResultsThe results of the LCMS/MS study of different extracts of T. cordifolia indicated presence of alkaloids, glycosides, terpenoids, sterols and sugars such as amritoside A, tinocordin, magnoflorine, N-methylcoclaurine, coridine, 20β-hydroxyecdysone and menaquinone-7 palmatin, cordifolioside A and tinosporine etc. Among all the three extracts, the hydroalcoholic extract (400 mg/kg) showed the highest response followed by aqueous and ethanolic extracts as evident in in vivo behavioral and biochemical evaluations. Furthermore, docking studies also exposed that these compounds viz. N-methylcoclaurine tinosporin, palmatine, tinocordin, 20β-hydroxyecdysone, and coridine exhibited well to excellent affinity towards target sEH protein. ConclusionT. cordifolia stem could alleviate neuropathic pain via soluble epoxide hydrolase inhibitory activity.

Comparison of the Effects of Botulinum Toxin Doses on Nerve Regeneration in Rats with Experimentally Induced Sciatic Nerve Injury.

This study was designed to compare the effects of various doses of botulinum neurotoxin A (BoNT/A) on nerve regeneration. Sixty-five six-week-old rats with sciatic nerve injury were randomly allocated to three experimental groups, a control group, and a sham group. The experimental groups received a single session of intraneural BoNT/A (3.5, 7.0, or 14 U/kg) injection immediately after nerve-crushing injury. The control group received normal intraneural saline injections after sciatic nerve injury. At three, six, and nine weeks after nerve damage, immunofluorescence staining, an ELISA, and toluidine blue staining was used to evaluate the regenerated nerves. Serial sciatic functional index analyses and electrophysiological tests were performed every week for nine weeks. A higher expression of GFAP, S100β, GAP43, NF200, BDNF, and NGF was seen in the 3.5 U/kg and 7.0 U/kg BoNT/A groups. The average area and myelin thickness were significantly greater in the 3.5 U/kg and 7.0 U/kg BoNT/A groups. The sciatic functional index and compound muscle action potential amplitudes exhibited similar trends. These findings indicate that the 3.5 U/kg and 7.0 U/kg BoNT/A groups exhibited better nerve regeneration than the 14 U/kg BoNT/A and control group. As the 3.5 U/kg and the 7.0 U/kg BoNT/A groups exhibited no statistical difference, we recommend using 3.5 U/kg BoNT/A for its cost-effectiveness.

Combination of stem cells and nerve guide conduit for the treatment of peripheral nerve injury: A meta-analysis.

Many small-sized, single-center preclinical studies have investigated the benefits of introducing stem cells into the interior of nerve conduit. The aims of this meta-analysis are to review and contrast the effects of various types of stem cells in in vivo models used to reconstruct peripheral nerve injuries (PNIs) and to assess the reliability and stability of the available evidence. A systematic search was conducted using Cochrane Library, Embase, PubMed, and Web of Science to identify studies conducted from January 1, 2000, to September 21, 2022, and investigate stem cell therapy in peripheral nerve reconstruction animal models. Studies that met the relevant criteria were deemed eligible for this meta-analysis. Fifty-five preclinical studies with a total of 1234 animals were incorporated. Stem cells demonstrated a positive impact on peripheral nerve regeneration at different follow-up times in the forest plots of five outcome indicators: compound muscle action potential (CMAP) amplitude, latency, muscle mass ratio, nerve conduction velocity, and sciatic functional index (SFI). In most comparisons, stem cell groups showed substantial differences compared with the control groups. The superior performance of adipose-derived stem cells (ADSCs) in terms of SFI, CMAP amplitude, and latency (p < .001) was identified. The findings consistently demonstrated a favorable outcome in the reconstruction process when utilizing different groups of stem cells, as opposed to control groups where stem cells were not employed.

An electroconductive hydrogel with injectable and self-healing properties accelerates peripheral nerve regeneration and motor functional recovery

Peripheral nerve regeneration and functional recovery are slow due to disruption of bioelectrical signal transmission. As a new therapeutic strategy, conductive hydrogels have been shown to promote the regeneration of electroactive tissue, especially nerve tissue. However, conventional conductive hydrogels made of physically doped conductive particles suffer from fragility, agglomeration, poor durability, and discontinuous transmission of electrical signals, severely limiting the migration of Schwann cells (SCs) and the remyelination of axons. Herein, a novel water-soluble conductive material was synthesized by grafting polyaniline (PANI) onto carboxymethyl chitosan (CMCS). Dual cross-linked hydrogels with injectable, self-healing, and conductive properties were created by adding CMCS-PANI (CP) to the dynamic gel network generated by the Schiff base reaction between aldehyde-based hyaluronic acid (ALHA) and CMCS. The prepared self-healing ALHA/CMCS/CP (ACCP) hydrogel had good biocompatibility, elastic modulus, and electrical conductivity that matched the sciatic nerve. The in vitro experiments indicated that ACCP3 (3 wt% CP) promoted the proliferation and migration of the SCs. Injection of ACCP3 into the crush injury site of the sciatic nerve reduced tissue resistivity, increased nerve conduction velocity, decreased the sciatic nerve functional index, enhanced the expression of neuronal axon-specific proteins, induced axon extension and remyelination, and prevented muscle denervation atrophy. Overall, the injectable self-healing conductive ACCP3 hydrogel, as a safe and effective neural tissue substitute, opens up a new way for the treatment of peripheral nerve injury and has potential clinical application.

Integration of microbiota and metabolomics reveals the analgesic mechanisms of emodin against neuropathic pain

Background and objectiveNeuropathic pain (NeP) induced dysbiosis of intestinal microbiota in chronic constriction injury (CCI) rats. Emodin has analgesic effect but the detailed mechanism is not clear at the present time. This study aims to explore the underling mechanism of action of emodin against NeP with in CCI model. MethodsMale SD rats (180–220 g) were randomly divided into three groups: sham group, CCI group, and emodin group. Behavioral tests were performed to evaluate the therapeutic effects of emodin on CCI model. Feces and spinal cords of all rats were collected 15 days after surgery. 16S rDNA sequencing, untargeted metabolomics, qPCR and ELISA were performed. ResultsMechanical withdrawal thresholds (MWT), thermal withdrawal latency (TWL) and Sciatic functional index (SFI) in emodin group were significantly higher than CCI group (P < 0.05). Emodin not only inhibited the expression of pro-inflammatory cytokines in the spinal cords and colonic tissue, but also increased the expression of tight junction protein in colonic tissue. 16S rDNA sequencing showed that emodin treatment changed the community structure of intestinal microbiota in CCI rats. Untargeted metabolomics analysis showed that 33 differential metabolites were screened out between CCI group and emodin group. After verification, we found that emodin increased the level of S-adenosylmethionine (SAM) and Histamine in the spinal cord of CCI rats. ConclusionEmodin was effective in relieving neuropathic pain, which is linked to inhibition inflammatory response, increasing the proportion of beneficial bacteria and beneficial metabolites.

A comparison between therapeutic effects of Salvia Officinalis. Extract, meloxicam and dexamethasone following acute sciatic nerve injury due to analgesic drug injection in rats

BackgroundAn intramuscular (IM) injection into gluteal muscle can lead to iatrogenic trauma to sciatic nerve. The drugs can be injected directly into sciatic or into the tissue adjacent to the nerve. Besides the direct damage to nerve due to needle and drug entrance to nerve tissue, the chemical nature of each drug activates immune system near healthy peripheral nerves in order to remove damaged tissues and start healing process. This immune system response has a great role in creating pathological pain and it makes functional recovery as a major challenge. Material methodIn this study, 25 adults male Fischer- Wistar rats were used. An analgesic drug (diclofenac) was injected in the muscles near sciatic nerve (4 groups) and also in sciatic nerve (1 group, nerve control group). For clinical assessment of sciatic nerves integrity, sciatic functional index test (SFI test) was done before, 1 day and 7 days after surgery. Treatments with meloxicam, dexamethasone and extract of Salvia Officinalis were started for 3 muscle groups and 1 group remained as a control muscle group. After 1 week, all the animals were euthanized under deep anesthesia and the sciatic nerves with surrounding muscles were removed and sent to histopathological examination. Resultsall three treatment groups showed decreased inflammatory process and increased repair regeneration in compare to control group. Although, the amount recovery in the dexamethasone group was significantly higher in compared to the control and other treatment groups. ConclusionThis study showed That IM injection of analgesic drug (Diclofenac), without direct damage to sciatic nerve, causes activation of the immune system and iatrogenic sciatic neuropathy. This study also showed therapeutic effects of two common drugs (NSAID and corticosteroids) and an extract of Salvia Officinalis. Treatment with all three drugs, decreased inflammatory response at injury site and increased recovery but Long-term usage of corticosteroids and NSAIDs can be challenging. The Salvia extract also have showed acceptable improvement effects with minimal side effects.

The outcome of polyethylene glycol fusion augmented by electrical stimulation in a delayed setting of nerve repair following neurotmesis in a rat model

PurposePolyethylene glycol is known to improve recovery following its use in repair of acute peripheral nerve injury. The duration till which PEG works remains a subject of intense research. We studied the effect of PEG with augmentation of 20Htz of electrical stimulation (ES) following neurorrhaphy at 48 h in a rodent sciatic nerve neurotmesis model.MethodTwenty-four Sprague Dawley rats were divided into 4 groups. In group I, the sciatic nerve was transected and repaired immediately. In group II, PEG fusion was done additionally after acute repair. In group III, repair and PEG fusion were done at 48 h. In group IV, ES of 20Htz at 2 mA for 1 h was added to the steps followed for group III. Weekly assessment of sciatic functional index (SFI), pinprick, and cold allodynia tests were done at 3 weeks and euthanized. Sciatic nerve axonal count and muscle weight were done.ResultsGroups II, III, and IV showed significantly better recovery of SFI (II: 70.10 ± 1.24/III: 84.00 ± 2.59/IV: 74.40 ± 1.71 vs I: 90.00 ± 1.38) (p < 0.001) and axonal counts (II: 4040 ± 270/III: 2121 ± 450/IV:2380 ± 158 vs I: 1024 ± 094) (p < 0.001) at 3 weeks. The experimental groups showed earlier recovery of sensation in comparison to the controls as demonstrated by pinprick and cold allodynia tests and improved muscle weights. Addition of electrical stimulation helped in better score with SFI (III: 84.00 ± 2.59 vs IV: 74.40 ± 1.71) (p < 0.001) and muscle weight (plantar flexors) (III: 0.49 ± 0.02 vs IV: 0.55 ± 0.01) (p < 0.001) in delayed repair and PEG fusions.ConclusionThis study shows that PEG fusion of peripheral nerve repair in augmentation with ES results in better outcomes, and this benefit can be demonstrated up to a window period of 48 h after injury.

Yüzme Egzersizinin Siyatik Sinir Hasarı Sonrasında Elektrofizyolojik Parametreler Üzerindeki İyileştirici Etkisi

The sciatic nerve damage can cause symptoms such as loss of muscle strength and pain as a result of trauma to the nerve due to pressure, stretching or cutting, as well as lifelong disability. Despite the increasing knowledge about sciatic nerve regeneration mechanisms, full functional recovery is still insufficient. It is well known that exercise improves overall health. The current study aimed to reveal the therapeutic effects of swimming exercises using electrophysiological methods in rats with experimental sciatic nerve injury. Eighteen male Wistar Albino rats were used in this study. The subjects were randomly divided into three groups (n=6): 1-Control (C), 2-Intact Exercise (IntE), 3-Operated Exercise (OpE) groups. Sciatic nerve injury was performed by inducing experimental damage to the left hind extremity sciatic nerve of rats. Swimming exercise was applied for 45 minutes a day, five days a week (25°C) for four weeks. The level of regeneration was evaluated by taking motor function test-sciatic function index and EMG recording performed at the beginning of the experiment (day 0), after nerve damage (day 3), and at the end of the experiment (day 35). It was determined that sciatic function index, amplitude of motor and sensory nerves, peak-peak amplitude, percentage of compound muscle action potential, motor and sensory nerve conduction velocities, which decreased after sciatic nerve injury, increased with swimming exercise (p

Epothilone B loaded in acellular nerve allograft enhanced sciatic nerve regeneration in rats.

Epothilone B (EpoB) is a microtubule-stabilizing agent with neuroprotective properties. This study examines the regenerative properties of ANA supplemented with EpoB on a sciatic nerve deficit in male Wistar rats. For this purpose, the 10mm nerve gap was filled with acellular nerve allografts (ANAs) containing EpoB at 0.1, 1, and 10nM concentrations. The sensorimotor recovery was evaluated up to 16 weeks after the operation. Real-time PCR, histomorphometry analysis, and electrophysiological evaluation were also used to evaluate the process of nerve regeneration. ANA/EpoB (0.1nM) significantly improved sensorimotor recovery in rats compared to ANA, ANA/EpoB (1nM), and ANA/EpoB (10nM) groups. This led to reduced muscle atrophy, improved sciatic functional index, and thermal paw withdrawal reflex latency, indicating nerve regeneration and target organ reinnervation. The electrophysiological and histomorphometry findings also confirmed the ANA/EpoB regenerative properties (0.1nM). EpoB only enhanced ANA regenerative properties at 0.1nM, with no therapeutic effects at higher concentrations. Totally, we concluded that ANA loaded with 0.1nM EpoB can effectively reconstruct the transected sciatic nerve in rats, likely by enhancing axonal sprouting and extension.

CDK5R1 promotes Schwann cell proliferation, migration, and production of neurotrophic factors via CDK5/BDNF/TrkB after sciatic nerve injury

Cyclin-dependent kinase 5 regulatory subunit 1 (CDK5R1) is necessary for central nervous system development and neuronal migration. At present, there are few reports about the role of CDK5R1 in peripheral nerve injury, and these need to be further explored. The CCK-8 and EdU assay was performed to examine cell proliferation. The migration ability of Schwann cells was tested by the cell scratch test. The apoptosis of Schwann cells was detected by flow cytometry. Sciatic nerve injury model in rats was established by crush injury. The sciatic function index (SFI) and the paw withdrawal mechanical threshold (PWMT) were measured at different time points. The results revealed that overexpression of CDK5R1 promoted the proliferation and migration of Schwann cells, and inhibited the apoptosis. Further studies found that pcDNA3.1-CDK5R1 significantly upregulated the expression of CDK5, BDNF and TrkB. More importantly, CDK5R1 promoted the recovery of nerve injury in rats. In addition, the CDK5 mediated BDNF/TrkB pathway was involved in the molecular mechanism of CDK5R1 on Schwann cells. It is suggested that the mechanism by which CDK5R1 promotes functional recovery after sciatic nerve injury is by CDK5 mediated activation of BDNF/TrkB signaling pathways.

Development and preclinical evaluation of bioactive nerve conduits for peripheral nerve regeneration: A comparative study.

In severe peripheral nerve injuries, nerve conduits (NCs) are good alternatives to autografts/allografts; however, the results the available devices guarantee for are still not fully satisfactory. Herein, differently bioactivated NCs based on the new polymer oxidized polyvinyl alcohol (OxPVA) are compared in a rat model of sciatic nerve neurotmesis (gap: 5mm; end point: 6 weeks). Thirty Sprague Dawley rats are randomized to 6 groups: Reverse Autograft (RA); Reaxon®; OxPVA; OxPVA+EAK (self-assembling peptide, mechanical incorporation); OxPVA+EAK-YIGSR (mechanical incorporation); OxPVA+Nerve Growth Factor (NGF) (adsorption). Preliminarily, all OxPVA-based devices are comparable with Reaxon® in Sciatic Functional Index score and gait analysis; moreover, all conduits sustain nerve regeneration (S100, β-tubulin) without showing substantial inflammation (CD3, F4/80) evidences. Following morphometric analyses, OxPVA confirms its potential in PNI repair (comparable with Reaxon®) whereas OxPVA+EAK-YIGSR stands out for its myelinated axons total number and density, revealing promising in injury recovery and for future application in clinical practice.

Type III NRG-1 plays a regulatory role in the regeneration process of nerves from the beginning of transplantation

The present study investigated the effect of type III Neuregulin-1 (NRG-1) on changes in the myelin sheath and the recovery of nerve function during the regeneration process following autologous nerve transplantation. Seventy-two Sprague–Dawley rats were divided into a Blank, Model and (antisense oligonucleotide, ASON) group. The Model and ASON groups of SD rats were subjected to autologous nerve transplantation, and the Blank group only had the sciatic nerve exposed. The Model and ASON groups were given local injections of 2 ml PBS buffer solution and 2 ml ASON of Type III NRG-1, respectively, the NRG-1 type III was inhibited by ASON. Changes in the sciatic nerve functional index (SFI) and conduction velocities were observed at different 6 time points. Regeneration of the myelin sheath was observed using transmission electron microscopy. Type III NRG-1 protein was detected using Western blotting and immunohistochemistry, and NRG-1 mRNA was detected using PCR. The SFI of the ASON group was lower than the Model group after transplantation. The conduction velocities of the ASON group on the 14th and 21st days after autologous nerve transplantation were lower than the Model group (P < 0.01). The protein and mRNA expression of type III NRG-1 in the ASON group was lower than the Model group at all 6 time points. The area of medullated nerve fibres was significantly different between the ASON group and the Model group on the 3rd day (P < 0.05), as was the number of medullated nerve fibres per unit area (P < 0.01). The diameter of axons was obviously different between the two groups (P < 0.01). Type III NRG-1 played an important regulatory role in the regeneration process of the nerve from the beginning of transplantation to the 28th day.

The potential protective effects of pre-injury exercise on neuroimmune responses following experimentally-induced traumatic neuropathy: a systematic review with meta-analysis.

Pre-clinical evidence shows that neuropathy is associated with complex neuroimmune responses, which in turn are associated with increased intensity and persistence of neuropathic pain. Routine exercise has the potential to mitigate complications of future nerve damage and persistence of pain through neuroimmune regulation. This systematic review aimed to explore the effect of pre-injury exercise on neuroimmune responses, and other physiological and behavioural reactions following peripheral neuropathy in animals. Three electronic databases were searched from inception to July 2022. All controlled animal studies assessing the influence of an active exercise program prior to experimentally-induced traumatic peripheral neuropathy compared to a non-exercise control group on neuroimmune, physiological and behavioural outcomes were selected. The search identified 17,431 records. After screening, 11 articles were included. Meta-analyses showed that pre-injury exercise significantly reduced levels of IL-1β (SMD: -1.06, 95% CI: -1.99 to -0.13, n=40), but not iNOS (SMD: -0.71 95% CI: -1.66 to 0.25, n=82). From 72 comparisons of different neuroimmune outcomes at different anatomical locations, vote counting revealed reductions in 23 pro-inflammatory and increases in 6 anti-inflammatory neuroimmune outcomes. For physiological outcomes, meta-analyses revealed that pre-injury exercise improved one out of six nerve morphometric related outcomes (G-ratio; SMD: 1.95, 95%CI: 0.77 to 3.12, n=20) and one out of two muscle morphometric outcomes (muscle fibre cross-sectional area; SMD: 0.91, 95%CI: 0.27 to 1.54, n=48). For behavioural outcomes, mechanical allodynia was significantly less in the pre-injury exercise group (SMD -1.24, 95%CI: -1.87 to -0.61) whereas no overall effect was seen for sciatic function index. Post hoc subgroup analysis suggests that timing of outcome measurement may influence the effect of pre-injury exercise on mechanical allodynia. Risk of bias was unclear in most studies, as the design and conduct of the included experiments were poorly reported. Preventative exercise may have potential neuroprotective and immunoregulatory effects limiting the sequalae of nerve injury, but more research in this field is urgently needed.

A favorable suture method for size-mismatched nerve transfer: comparison with standard perineural suture in an experimental rat study

BackgroundIn nerve transfer for peripheral nerve injury, it is sometimes necessary to suture size-mismatched nerves. In 1993, a favorable suture method called the Ochiai suture method for size-mismatched nerve transfer was reported. However, there is currently a lack of substantial evidence beyond the original report. Therefore, this study aimed to verify the advantages of using the Ochiai suture method for size-mismatched nerve transfer.MethodsA total of 18 rats were evaluated in this study and randomly divided into two groups. All rats underwent femoral to sciatic nerve transfer. Specifically, group A (n = 10) underwent the Ochiai suture method, while group B (n = 8) underwent the perineural suture method. After 12 weeks postoperatively, we conducted the sciatic functional index (SFI) test, measured muscle wet-weight, and performed histological evaluations. All data were compared between the two groups, with Welch’s t test for normally distributed data and Mann-Whitney's U test for non-normally distributed data. Statistical significance was set at p < 0.05.ResultsThe mean number of axons was significantly greater in group A than in group B at 5 mm distal to the stump (p = 0.04). Additionally, the average axonal diameter was significantly greater in group A than in group B at 5 mm and 10 mm distal to the stump (p < 0.01 and p < 0.01, respectively). However, the SFI test and measured muscle wet-weight values showed no significant differences between the two groups.ConclusionsOur study revealed that the Ochiai suture method for size-mismatched nerve transfer in rats increases the regenerative axon numbers and diameters. These findings suggest that the Ochiai suture method could be a valuable approach for achieving effective motor function restoration in cases of size-mismatched nerve transfer.

ПАРАМЕТРЫ ПОХОДКИ КРЫС С ПЕРИФЕРИЧЕСКОЙ НЕЙРОПАТИЕЙ ПРИ ТРАНСПЛАНТАЦИИ МЕЗЕНХИМАЛЬНЫХ СТВОЛОВЫХ КЛЕТОК И ФАРМАКОЛОГИЧЕСКОЙ СТИМУЛЯЦИИ КАННАБИНОИДНЫХ РЕЦЕПТОРОВ II ТИПА

Background. The study of the role of cannabinoid CB2 receptors in the effectiveness of adipose-derived (AD) mesenchymal stem cells (MSCs) in preventing motor activity disorders in the affected limb will deepen understanding of the mechanisms of MSCs effects when administered locally. Aim. To evaluate the effect of pharmacological stimulation of cannabinoid CB2 receptors during transplantation of AD MSCs on changes in gait parameters in rats in a model of peripheral neuropathy. Material and methods. In 40 male Wistar rats peripheral neuropathic pain was modeled by sciatic nerve transection. On the 7th day after NP modeling, AD MSCs transplantation was performed without additional interventions upon the pharmacological stimulation of CB2 receptors in the area of sciatic nerve transection, as well as after stimulation of CB2 receptors on the AD MSCs membranes during pretreatment. Within 90 days a detailed analysis of the gait was carried out using the CatWalk XT 10.6. Results. Transplantation of AD MSCs accelerated the recovery of dynamic gait parameters, as well as sciatic functional index, and abolished the development of static gait disturbances in rats after sciatic nerve transection. Significant differences in the analyzed gait parameters in the study groups with AD MSCs transplantation were not found. Conclusion. Pharmacological stimulation of CB2 receptors did not enhance or suppress the effect of AD MSCs on the rate of recovery of gait parameters in experimental animals.

Betulinic acid alleviates neuropathic pain induced by chronic constriction injury of the sciatic nerve in mice

Neuropathic pain refers to a type of pain that arises from primary damage and dysfunction within the nervous system. Addressing this condition presents significant challenges and complexities. Betulinic acid (BA), known for its potent antioxidative and anti-inflammatory properties, has garnered extensive attention; nevertheless, the impact upon neuropathic pain induced by CCI is still uncertain. This paper explores the analgesic effects concerning BA on mice experiencing neuropathic pain due to sciatic nerve injury. Throughout the experiment, mice with CCI received oral gavage of BA at dosages of 3, 10, and 30 mg/kg for consecutively 8 days from the 7th day post-surgery. To assess their responses, behavioral tests and sciatic functional index (SFI) evaluations were conducted on zeroth, seventh, eighth, tenth, twelveth and fourteenth day post-CCI. On day 14, histopathological examinations and measurements of biochemical markers were performed. Immunofluorescence techniques were employed to detect Nrf2 and glial cell activation, while the Western blot method was utilized to evaluate Nrf2/HO-1 protein levels and pro-inflammatory cytokine expression. The results elucidated that BA significantly alleviated hyperalgesia and allodynia, demonstrating a dose-dependent enhancement in sciatic nerve function and facilitating the recovery of sciatic nerve injury. Furthermore, BA prominently augmented the entire antioxidative capacity (T-AOC) and T-SOD levels, concomitantly reducing MDA concentrations. Notably, BA activated the Nrf2/HO-1 signaling pathway, inhibited glial cell activation, and downregulation of the expression levels of pro-inflammatory cytokines, specifically, TNF-α, IL-1β, and IL-6 were observed. As such, this study provides a basis to support BA as a candidate drug for the treatment of neuropathic pain, attributing its analgesic effects to its anti-inflammatory, antioxidative, and neuroprotective properties.