PLCL/SF/NGF nerve conduit loaded with RGD-TA-PPY hydrogel promotes regeneration of sciatic nerve defects in rats through PI3K/AKT signalling pathways.

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

A tacrolimus-eluting nerve guidance conduit enhances regeneration in a critical-sized peripheral nerve injury rat model.

Critical-sized peripheral nerve injuries pose a significant clinical challenge and lead to functional loss and disability. Current regeneration strategies, including autografts, synthetic nerve conduits, and biologic treatments, encounter challenges such as limited availability, donor site morbidity, suboptimal recovery, potential immune responses, and sustained stability and bioactivity. An obstacle in peripheral nerve regeneration is the immune response that can lead to inflammation and scarring that impede the regenerative process. Addressing both the immunological and regenerative needs is crucial for successful nerve recovery. Here, we introduce a novel biodegradable tacrolimus-eluting nerve guidance conduit engineered from a blend of poly (L-lactide-co-caprolactone) to facilitate peripheral nerve regeneration and report the testing of this conduit in 15-mm critical-sized gaps in the sciatic nerve of rats. The conduit's diffusion holes enable the local release of tacrolimus, a potent immunosuppressant with neuro-regenerative properties, directly into the injury site. A series of in vitro experiments were conducted to assess the ability of the conduit to maintain a controlled tacrolimus release profile that could promote neurite outgrowth. Subsequent in vivo assessments in rat models of sciatic nerve injury revealed significant enhancements in nerve regeneration, as evidenced by improved axonal growth and functional recovery compared to controls using placebo conduits. These findings indicate the synergistic effects of combining a biodegradable conduit with localized, sustained delivery of tacrolimus, suggesting a promising approach for treating peripheral nerve injuries. Further optimization of the design and long-term efficacy studies and clinical trials are needed before the potential for clinical translation in humans can be considered.

Developing long bones respond to surrounding tissues by trans-pairing of periosteal osteoclasts and endocortical osteoblasts.

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

Giant sciatic nerve schwannoma: a rare case report and literature review.

Introduction and importance: Schwannomas are benign tumors that arise from Schwann cells commonly located in peripheral nerves. Depending on the size and location of sciatic nerve Schwannoma clinical manifestations can either varies from symptoms simulating radiculopathies such as positive Lasegue sign on the affected side, gait weakness and paresthesia or just present with pain and an associated palpable mass. Case presentation: The authors present a case of a 34-year-old female patient suffering from pain, gait weakness, and a palpable mass since many months. The palpable mass was present in the posterior region of the left lower limb. Imaging studies reveal an extensive lesion measuring 35 cm×8 cm that extends from the gluteal region to the left popliteal fossa. Clinical discussion: The finding of a palpable mass during physical examination guided us towards the diagnostic suspicion and thus necessitating the direct imaging studies. When approaching such type of patients, a history of neurofibromatosis must be ruled out due to its frequent association. Surgical resection should focus on the preservation of neurovascular structures, which offers improvement of the symptoms and the quality of life of patients. Conclusion: Giant sciatic nerve schwannoma if excised completely can lead to relieve of symptoms. Although recurrences are uncommon follow-up for years is necessary.

Triple case report of persistent sciatic artery in Ethiopia: a rare vascular anomaly.

Persistent sciatic artery (PSA) is a rare congenital vascular anomaly resulting from embryologic axial artery malformation in the lower limb. This case report presents three patients aged 45-60, each with bilateral PSA presenting with symptoms indicative of PSA complications, including aneurysmal degeneration, limb ischemia, thromboembolism, or neuralgia from nerve compression. It highlights the diagnostic process, management strategies, and clinical outcomes observed at a tertiary referral hospital. Treatment involved a collaborative, multidisciplinary approach with vascular surgeons, internists, and radiologists tailoring interventions to individual patient findings and disease progression. This report aims to provide insights into the diverse presentations and management of PSA in a resource limited setting, encouraging further reporting and case studies to enhance understanding of therapeutic outcomes.

Direct dorsal root ganglia (DRG) injection in mice for analysis of adeno-associated viral (AAV) gene transfer to peripheral somatosensory neurons.

BACKGROUND: Delivering optogenetic genes to the peripheral sensory nervous system provides an efficient approach to study and treat neurological disorders and offers the potential to reintroduce sensory feedback to prostheses users and those who have incurred other neuropathies. Adeno-associated viral (AAV) vectors are a common method of gene delivery due to efficiency of gene transfer and minimal toxicity. AAVs are capable of being designed to target specific tissues, with transduction efficacy determined through the combination of serotype and genetic promoter selection, as well as location of vector administration. The dorsal root ganglia (DRGs) are collections of cell bodies of sensory neurons which project from the periphery to the central nervous system (CNS). The anatomical make-up of DRGs make them an ideal injection location to target the somatosensory neurons in the peripheral nervous system (PNS). COMPARISON TO EXISTING METHODS: Previous studies have detailed methods of direct DRG injection in rats and dorsal horn injection in mice, however, due to the size and anatomical differences between rats and strains of mice, there is only one other published method for AAV injection into murine DRGs for transduction of peripheral sensory neurons using a different methodology. NEW METHOD/RESULTS: Here, we detail the necessary materials and methods required to inject AAVs into the L3 and L4 DRGs of mice, as well as how to harvest the sciatic nerve and L3/L4 DRGs for analysis. This methodology results in optogenetic expression in both the L3/L4 DRGs and sciatic nerve and can be adapted to inject any DRG.

The anatomical course of the sciatic nerve in relation to different approaches in total hip arthroplasty.

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

Exercise as a promising alternative for sciatic nerve injury pain relief: a meta-analysis.

Objective: The efficacy of drug therapies in managing neuropathic pain is constrained by their limited effectiveness and potential for adverse effects. In contrast, exercise has emerged as a promising alternative for pain relief. In this study, we conducted a systematic evaluation of the therapeutic impact of exercise on neuropathic pain resulting from sciatic nerve injury in rodent models. Methods: The PubMed, Embase, and Web of Science databases were retrieved before April 2024. A series of studies regarding the effect of treadmill, swimming, wheel and other exercises on neuropathic pain induced by sciatic nerve injury in rats and mice were collected. Using predefined inclusion criteria, two researchers independently performed literature screening, data extraction, and methodological quality assessment utilizing SYRCLE's risk of bias tool for animal studies. Statistical analysis was conducted using RevMan 5.3 and STATA 12.0 analysis software. Results: A total of 12 relevant academic sources were included in the analysis of controlled animal studies, with 133 rodents in the exercise group and 135 rodents in the sedentary group. The meta-analysis revealed that exercise was associated with a significant increase in paw withdrawal mechanical threshold [Standard Mean Difference (SMD) = 0.84, 95% confidence interval (CI): 0.28-1.40, p = 0.003] and paw withdrawal thermal latency (SMD = 1.54, 95%CI: 0.93-2.15, p < 0.0001) in rats and mice with sciatic nerve injury. Subgroup analyses were conducted to evaluate the impact of exercise duration on heterogeneity. The results showed that postoperative exercise duration ≤3 weeks could significantly elevate paw withdrawal mechanical threshold (SMD = 1.04, 95% CI: 0.62-1.46, p < 0.00001). Postoperative exercise duration ≤4 weeks could significantly improve paw withdrawal thermal latency (SMD = 1.93, 95% CI:1.19-2.67, p < 0.00001). Conclusion: Exercise represents an effective method for improving mechanical and thermal hypersensitivity resulting from sciatic nerve injury in rodents. Factors such as pain models, the initiation of exercise, the type of exercise, and the species of rodent do not significantly impact the development of exercise-induced hypoalgesia. However, the duration of postoperative exercise plays a crucial role in the onset of exercise-induced hypoalgesia.

Quantitation of the physicochemical properties of myelin using Nile Red fluorescence spectroscopy.

Myelin is a vital structure that is key to rapid saltatory conduction in the central and peripheral nervous systems. Much work has been done over the decades examining the biochemical composition and morphology of myelin at the light and electron microscopic levels. Here we report a method to study myelin based on the fluorescent probe Nile Red. This lipophilic dye readily partitions into live and chemicallyfixed myelin producing bright, well-resolved images of the sheath. Using spectral confocal microscopy, a complete emission spectrum of Nile Red fluorescence can be acquired for each pixel in an image. The solvatochromic properties of Nile Red cause its emission spectrum to change depending on the polarity of its local environment. Therefore, measuring spectral shifts can report subtle changes in the physicochemical properties of myelin. We show differences in myelin polarity in central versus peripheral nervous system and in different regions of central nervous system white matter of the mouse brain, together with developmental and sex variations. This technique is also well suited for measuring subtle changes in myelin properties in live ex vivo white matter specimens. We also demonstrate how light deprivation induces a myelin polarity change in adult mouse optic nerve underscoring a continuing myelin plasticity in response to axonal activity well into adulthood. The Nile Red spectroscopic method allows measurement of subtle physicochemical changes in myelin that can importantly influence its electrical properties and by extension, conduction velocities in axons.

Knowledge and Attitude Toward Sciatica Pain and Treatment Methods Among the Population of Qassim in Saudi Arabia: A Cross-Sectional Study.

Background: Sciatica, a pain radiating along the sciatic nerve, can cause significant suffering and functional limitations. Understanding individual populations' knowledge and attitudes about sciatica pain is crucial for designing targeted interventions and enhancing healthcare delivery, especially in Saudi Arabia. This study aimed to evaluate the knowledge and attitude toward sciatica pain and treatment methods among the population of Al-Qassim in Saudi Arabia. Methods and materials:This online cross-sectional study was conducted in the Al-Qassim region, Saudi Arabia, using a self-administered questionnaire. The data was analyzed using SPSS software, with numeric data presented as mean ± SD and categorical variables as frequencies and percentages. Correlation analyses included the Chi-squared test and one-way ANOVA. Results: The study received 398 responses, from mostly female (n=305, 76.6%) and Saudi adults aged under 30 (n=248, 62.3%). Most participants sought treatment for sciatica pain from a specialist doctor (n=28, 56.0%) or a general doctor (n=10, 20.0%). Physical therapy was the most common self-treatment method (n=11, 32.4%), followed by painkillers and muscle relaxants (n=10, 29.4%). Knowledge and attitude toward sciatica were generally low (mean score: 3.54 ± 2.61 out of 9), with only 70 (17.6%) showing good knowledge. Most respondents recognized practices like spinal imaging, surgery as a last resort, and exercise/sitting habits as impacting sciatica outcomes. Traditional therapies like massage, cupping, acupuncture, and cautery were considered beneficial. Educational level significantly impacted knowledge scores, with higher mean scores among postgraduate education holders and bachelor's degree holders (mean scores: 4.06 ± 2.48 and 3.98 ± 2.53, respectively). Age, gender, occupation, nationality, and region showed no significant differences in mean knowledge scores. Attitude scores were similar across sociodemographic spectra, with younger respondents having slightly more positive attitudes.  Conclusion: The study showed poor knowledge, influenced by education levels, and neutral attitudes about sciatica among residents of Al-Qassim. Therefore, educational programs and engagement of healthcare stakeholders are recommended to raise awareness and improve knowledge and attitudes.

Sciatic nerve stimulation alleviates neuropathic pain and associated neuroinflammation in the dorsal root ganglia in a rodent model.

BACKGROUND: Satellite glial cells (SGCs) in the dorsal root ganglia (DRG) play a pivotal role in the formation of neuropathic pain (NP). Sciatic nerve stimulation (SNS) neuromodulation was reported to alleviate NP and reduce neuroinflammation. However, the mechanisms underlying SNS in the DRG remain unclear. This study aimed to elucidate the mechanism of electric stimulation in reducing NP, focusing on the DRG. METHODS: L5 nerve root ligation (NRL) NP rat model was studied. Ipsilateral SNS performed 1 day after NRL. Behavioral tests were performed to assess pain phenotypes. NanoString Ncounter technology was used to explore the differentially expressed genes and cellular pathways. Activated SGCs were characterized in vivo and in vitro. The histochemical alterations of SGCs, macrophages, and neurons in DRG were examined in vivo on post-injury day 8. RESULTS: NRL induced NP behaviors including decreased pain threshold and latency on von Frey and Hargreaves tests. We found that following nerve injury, SGCs were hyperactivated, neurotoxic and had increased expression of NP-related ion channels including TRPA1, Cx43, and SGC-neuron gap junctions. Mechanistically, nerve injury induced reciprocal activation of SGCs and M1 macrophages via cytokines including IL-6, CCL3, and TNF-α mediated by the HIF-1α-NF-κB pathways. SNS suppressed SGC hyperactivation, reduced the expression of NP-related ion channels, and induced M2 macrophage polarization, thereby alleviating NP and associated neuroinflammation in the DRG. CONCLUSIONS: NRL induced hyperactivation of SGCs, which had increased expression of NP-related ion channels. Reciprocal activation of SGCs and M1 macrophages surrounding the primary sensory neurons was mediated by the HIF-1α and NF-κB pathways. SNS suppressed SGC hyperactivation and skewed M1 macrophage towards M2. Our findings establish SGC activation as a crucial pathomechanism in the gliopathic alterations in NP, which can be modulated by SNS neuromodulation.

Left distal sciatic giant solitary myxoid neurofibroma: a case report & literature review.

Introduction: Neurofibroma, a rare benign tumor of the peripheral nervous system, can manifest anywhere along a nerve from the dorsal ganglion to its terminal branches. Myxoid neurofibroma can present as a solitary non-tender nodule and is often confirmed by positive immunohistochemical staining for S-100 protein. However, in 50% of cases, neurofibromas are associated with neurofibromatosis. Case presentation: We present a case of a 34-year-old male with mild pain in the posterior part of his left thigh, accompanied by a slowly-growing swelling particularly noticeable when flexing his knee. It had gradually increased in size over several months, which the patient observed as a decrease in the degree of knee extension. Initial biopsy indicated schwannoma with no evidence of malignancy. Four years later, the swelling increased in size and necessitated resection surgery, revealing an irregular giant tumor measuring 8 *6 *4.5 cm, adherent to adjacent structures, including the femur, muscles, popliteal artery and vein, and a branch of the sciatic nerve. Pathological analysis reclassified the diagnosis to low-grade myxoid neurofibroma. Follow-up MRI three months later showed gross total resection without residual or recurrence of the tumor. Discussion: Solitary neurofibromas are often small in size, ranging from 1 to 2 cm in the greatest dimension. Alternatively, tumors that occur as a part of genetic neurofibromatosis tend to be multiple and often grow to large sizes. In our case, the patient didn't have neurofibromatosis as he didn't meet its diagnostic criteria despite having a giant tumor measuring approximately 8*6*4.5 cm. To our knowledge, this is the first report of giant myxoid solitary neurofibroma of the thigh apart from neurofibromatosis. Thus, this type of tumor should be considered in the differential diagnosis of tumors at this location.

Efficacy of ultrasound-guided classical versus parasacral parallel shift technique of sacral plexus block for lower limb surgeries - A randomised controlled trial.

Background and Aims: Ultrasound-guided sacral plexus block has been used for anaesthesia and analgesia in lower limb surgeries. This study aimed to compare the block performance characteristics after ultrasound-guided (USG) sacral plexus nerve block (SNB) using the parasacral parallel shift (PSPS) approach versus the classical approach in patients undergoing orthopaedic below-knee limb surgeries. Methods: In this randomised study, 144 adult patients were randomised to receive USG SNB either by the classical approach (Group C) or the PSPS approach (Group P). A fixed dose of 20 ml of 0.5% ropivacaine was administered. Patients also received USG femoral nerve block with 10 ml of 0.5% ropivacaine. The primary outcome was the scanning time between the two groups. Secondary outcomes were the needling time, sensory and motor block onset and postoperative analgesic characteristics between the two groups. A P value of <0.05 was considered statistically significant. Results: The needling time and the scanning time were significantly lesser in Group P than in Group C (P < 0.05). Complete sensory and motor nerve blockade of the sciatic nerve was significantly higher in Group P (P = 0.029). Block performance time, time for sensory block and time for motor block were significantly less in Group P compared to Group C (P < 0.001). The postoperative analgesic characteristics were comparable between the two groups. Conclusion: The sacral plexus block with ultrasound-guided parasacral parallel shift technique had a lower block performance time with lesser needling and scanning time than the classical approach.

Prevention and reversal of neuropathic pain by near-infrared photobiomodulation therapy in male and female rats.

Pathological nociception arising from peripheral nerve injury impacts quality of life. Current therapeutics are generally ineffective. However, photobiomodulation therapy (PBMT) has shown promise in addressing this issue. We aimed to assess the potential anti-allodynic effects of 2 p.m. protocols, each applied transcutaneously over the peripheral nerve injury. In addition to evaluating nociceptive behavior, we also conducted morphological analysis using electron microscopy (EM) to investigate potential ultrastructural changes at the cellular level. We sought to determine, using the chronic constriction injury (CCI) model, whether our parameters could alleviate established allodynia and/or dampen allodynia development. Adult male and female rats with CCI or sham were treated with PBMT (850-nm wavelength) for 2 min, 3 times a week over three or four weeks across three studies, where PBMT began either before or after CCI. Allodynia was assessed prior to surgery and across weeks and, at the conclusion of the third study, sciatic nerve was processed for EM and histomorphometrically evaluated. The results showed that PBMT before versus after CCI injury yielded similar behaviors, effectively decreasing allodynia. Interestingly, these positive effects of PBMT do not appear to be accounted by protection of the sciatic injury site, based on EM. CCI reliably decreased axon size and the number of myelinated axons present in both PBMT and control groups. While PBMT reduced the number of C-fibers in CCI samples, no improvement in any measure was observed in response to PBMT.

Improved Neurotization in High Peripheral Nerve Injury: Side to Side H-shaped Nerve Graft at the Most Distal Part of an Injured Extremity in a Rabbit Model.

Background: We aimed to investigate the effects of nerve repair by setting a side-to-side (H-shaped) nerve graft on the most distal part of the damaged nerve to the adjacent intact nerve to accelerate its regeneration in the end organ. Methods: This pure experimental study was done on the lower extremities of two groups of rabbits in Animal Laboratory Department, 15 Khordad Hospital Tehran, Iran. In both groups, the sciatic nerve at the proximal part of the extremity below the superficial femoral branch was first cut and then repaired. In the investigation group, side-to-side H-shaped nerve grafts were applied between the sciatic and superficial femoral nerves (i.e., two branches) at the most distal to the cut site of the sciatic nerve below the superficial femoral branch at the lower extremity. The sciatic nerve was conventionally repaired in the control group. Results: None of the rabbits' feet in the control group respond to pain stimulation (were without senses) and had ulcers. They had numb legs and went lame. All had muscular atrophy and lacked nerve growth (regeneration) according to pathology. In the investigation group, 86.7% of the rabbits responded to pain stimulation and only 13.3% of them had ulcers. In addition, in pathology report, 13.3% had suffered muscular atrophy and lacked nerve regeneration. Therefore, nerve regeneration was successful in 86.7% of rabbits who underwent H-shaped nerve grafts. Conclusion: Side-to-side H-shaped nerve graft at the most distal part of an injured nerve may cause successful recovery of high (proximal) nerve injury.

Automated peripheral nerve segmentation for MR-neurography.

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

Anethole Prevents the Alterations Produced by Diabetes Mellitus in the Sciatic Nerve of Rats.

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

Exploring the Therapeutic Potential of Mesenchymal Stem Cells-derived conditioned medium: An In-depth Analysis of Pain Alleviation, Spinal CCL2 Levels, and Oxidative Stress.

Neuropathic pain, a debilitating condition, remains a significant challenge due to the lack of effective therapeutic solutions. This study aimed to evaluate the potential of mesenchymal stromal cell (MSC)-derived conditioned medium in alleviating neuropathic pain induced by sciatic nerve compression injury in adult male rats. Forty Wistar rats were randomly assigned to four groups: control, nerve injury, nerve injury with intra-neural injection of conditioned medium, and nerve injury with intra-neural injection of culture medium. Following sciatic nerve compression, the respective groups received either 10 µl of conditioned medium from amniotic fluid-derived stem cells or an equal volume of control culture medium. Behavioral tests for cold allodynia, mechanical allodynia, and thermal hyperalgesia were conducted, and the spinal cord was analyzed using Western Blot and oxidative stress assays. The behavioral experiments showed a decrease in mechanical hyperalgesia and cold allodynia in the group receiving conditioned medium compared to the injury group and the control medium group. Western blot data revealed a decrease in the expression of the CCL2 protein and an increase in GAD65. Oxidative stress tests also showed increased levels of SOD and glutathione in conditioned media-treated animals compared to animals with nerve injury. The findings suggest that conditioned medium derived from amniotic fluid-derived stem cells can effectively reduce neuropathic pain, potentially through the provision of supportive factors that mitigate oxidative stress and inflammation in the spinal cord.

Exosomes repairment for sciatic nerve injury: a cell-free therapy.

Sciatic nerve injury (SNI) is a common type of peripheral nerve injury typically resulting from trauma, such as contusion, sharp force injuries, drug injections, pelvic fractures, or hip dislocations. It leads to both sensory and motor dysfunctions, characterized by pain, numbness, loss of sensation, muscle atrophy, reduced muscle tone, and limb paralysis. These symptoms can significantly diminish a patient's quality of life. Following SNI, Wallerian degeneration occurs, which activates various signaling pathways, inflammatory factors, and epigenetic regulators. Despite the availability of several surgical and nonsurgical treatments, their effectiveness remains suboptimal. Exosomes are extracellular vesicles with diameters ranging from 30 to 150 nm, originating from the endoplasmic reticulum. They play a crucial role in facilitating intercellular communication and have emerged as highly promising vehicles for drug delivery. Increasing evidence supports the significant potential of exosomes in repairing SNI. This review delves into the pathological progression of SNI, techniques for generating exosomes, the molecular mechanisms behind SNI recovery with exosomes, the effectiveness of combining exosomes with other approaches for SNI repair, and the changes and future outlook for utilizing exosomes in SNI recovery.

Efficacy of using adipose-derived stem cells and PRP on regeneration of 40 -mm long sciatic nerve defect bridged by polyglycolic-polypropylene mesh in canine model.

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