ObjectiveTo investigate the effect of folic acid coated-crosslinked urethane-doped polyester elastomer (fCUPE) nerve conduit in repairing long distance peripheral nerve injury. MethodsThirty-six 3-month-old male Sprague Dawley rats weighing 180-220 g were randomly assigned to 3 groups, each consisting of 12 rats: CUPE nerve conduit transplantation group (group A), fCUPE nerve conduit transplantation group (group B), and autologous nerve transplantation group (group C), the contralateral healthy limb of group C served as the control group (group D). A 20-mm-long sciatic nerve defect model was established in rats, and corresponding materials were used to repair the nerve defect according to the group. The sciatic function index (SFI) of groups A-C was calculated using the Bain formula at 1, 2, and 3 months after operation. The nerve conduction velocity (NCV) of the affected side in groups A-D was assessed using neuroelectrophysiological techniques. At 3 months after operation, the regenerated nerve tissue was collected from groups A-C for S-100 immunohistochemical staining and Schwann cell count in groups A and B to compare the level of nerve repair and regeneration in each group. ResultsAt 3 months after operation, the nerve conduits in all groups partially degraded. There was no significant adhesion between the nerve and the conduit and the surrounding tissues, the conduit was well connected with the distal and proximal nerves, and the nerve-like tissues in the conduit could be observed when the nerve conduit stents were cut off. SFI in group A was significantly higher than that in group C at each time point after operation and was significantly higher than that in group B at 2 and 3 months after operation (P<0.05). There was no significant difference in SFI between groups B and C at each time point after operation (P>0.05). NCV in group A was significantly slower than that in the other 3 groups at each time point after operation (P<0.05). The NCV of groups B and C were slower than that of group D, but the difference was significant only at 1 month after operation (P<0.05). There was no significant difference between groups B and C at each time point after operation (P>0.05). Immunohistochemical staining showed that the nerve tissue of group A had an abnormal cavo-like structure, light tissue staining, and many non-Schwann cells. In group B, a large quantity of normal neural structures was observed, the staining was deeper than that in group A, and the distribution of dedifferentiated Schwann cells was obvious. In group C, the nerve bundles were arranged neatly, and the tissue staining was the deepest. The number of Schwann cells in group B was (727.50±57.60) cells/mm2, which was significantly more than that in group A [(298.33±153.12) cells/mm2] (t=6.139, P<0.001). ConclusionThe fCUPE nerve conduit is effective in repairing long-distance sciatic nerve defects and is comparable to autologous nerve grafts. It has the potential to be used as a substitute material for peripheral nerve defect transplantation.
Objective To summarize application effect and clinical experience of multimodal intraoperative neurophysiological monitoring (IONM) technology in the surgery of neurofibromatosis type 1 (NF1) related peripheral nerve tumors. Methods A retrospective study was conducted on NF1 patients, who admitted between January 2019 and December 2023 and treated with peripheral nerve tumor resection surgery assisted by multimodal IONM technology. There were 49 males and 45 females. The age ranged from 5 to 78 years, with an average of 33.7 years. Tumor morphological classification included 71 cases of nodular type, 13 cases of diffuse type, and 10 cases of mixed type. Target tumors were distributed in craniofacial region (47 cases), neck (11 cases), trunk (12 cases), and limbs (24 cases). Preoperatively, 44 cases had no obvious neurological symptoms, while the remaining patients had neurological symptoms, including 15 cases of visual impairment, 5 cases of hearing impairment, 16 cases of somatic movement disorders, and 31 cases of somatic sensory disorders, of which 7 cases had more than one symptom. IONM plans were selected based on the relevant nerves and adjacent important structures of the target tumor, including visual evoked potential (17 cases), somatosensory evoked potential (44 cases), motor evoked potential (88 cases), and electromyogram (94 cases).Results All surgeries were successfully completed. Ninety-three patients underwent total/near total resection and 1 patient underwent palliative resection. Pathological examination showed 80 cases of neurofibroma and 14 cases of malignant peripheral nerve sheath tumors. Complications included 2 cases of hematoma and 3 cases of incision infection. All patients were followed up 3-61 months (median, 15 months). During follow-up, no significant changes in neurological symptoms or tumor recurrence were found. Among the patients with preoperative visual impairment, there were 14 cases with no improvement in symptoms and 1 with improvement after surgery. Among the patients with somatic movement disorders, there were 11 cases with no improvement in symptoms, 3 cases with improvement, 2 cases with aggravation, 4 newly onset cases, and 1 case with significant impact on daily life after surgery. Among the patients with somatic sensory disorders, there were 17 cases with no improvement in symptoms, 14 cases with improvement, and 13 newly onset cases. The patients with hearing impairment showed improvement after surgery. Conclusion The clinical manifestations of NF1 related peripheral nerve tumors are complex. Multimodal IONM technology can provide real-time detection of nerve provocation and damage. Surgical treatment with multimodal IONM technology is safe and can reduce complications.
ObjectiveTo review the literature on the research status of vascularization of tissue engineered peripheral nerve so as to provide the theoretical basis for the vascularization of tissue engineered peripheral nerve.MethodsThe literature related to the vascularization of peripheral nerve tissue engineering in recent years was reviewed and summarized according to the five aspects of promoting vascularization: local microenvironment and blood supply characteristics of peripheral nerve regeneration, scaffold material modification, seed cells, autologous vascular bundle implantation, and pro-vascular factors.ResultsTissue engineered peripheral nerve has brought a new hope for the repair of peripheral nerve injury, but the repair effect of large nerve defects is not good, which is mainly related to the degree of vascularization of the nerve grafts. So it is particularly important to promote the early vascularization of tissue engineered peripheral nerve. Previous studies have mainly focused on the four aspects of scaffold material modification, seed cells, autologous vascular bundle implantation, and angiogenesis related factors. Recent studies show that the combination of the above two or more factors in the tissue engineered peripheral nerves can better promote the vascularization of tissue engineered peripheral nerves.ConclusionPromoting early vascularization of tissue engineered peripheral nerves can provide timely nutritional support for seed cells on the scaffold, promote axon growth and nerve regeneration, and facilitate the repair of large peripheral nerve defects in clinical practice.
Objective To explore the role and clinical significance of cell-cycle dependent kinase 1 (CDK1) and its upstream and downstream molecules in the development of malignant peripheral nerve sheath tumor (MPNST) through the analysis of clinical tissue samples. Methods A total of 56 tumor samples from MPNST patients (“Tianjin” dataset) who underwent surgical resection, confirmed by histology and pathology between September 2011 and March 2020, along with 17 normal tissue samples, were selected as the research subjects. MPNST-related hub genes were identified through transcriptome sequencing, bioinformatics analysis, immunohistochemistry staining, and survival analysis, and their expression levels and prognostic associations were analyzed. Results Transcriptome sequencing and bioinformatics analysis revealed that upregulated genes in MPNST were predominantly enriched in cell cycle-related pathways, with CDK1 occupying a central position among all differentially expressed genes. Further differential analysis demonstrated that CDK1 mRNA expression in sarcoma tissues was significantly higher than in normal tissues [based on searching the cancer genome atlas (TCGA) dataset, P<0.05]. In MPNST tissues, CDK1 mRNA expression was not only significantly higher than in normal tissues (based on Tianjin, GSE141438 datasets, P<0.05), but also significantly higher than in neurofibromatosis (NF) and plexiform neurofibromas (PNF) (based on GSE66743 and GSE145064 datasets, P<0.05). Immunohistochemical staining results indicated that the expression rate of CDK1 protein in MPNST tissues was 40.31%. Survival analysis results demonstrated that CDK1 expression was associated with poor prognosis. The survival time of MPNST patients with high CDK1 mRNA expression was significantly lower than that of the low expression group (P<0.05), and the overall survival trend of patients with positive CDK1 protein expression was worse than that of patients with negative CDK1 expression. Additionally, differential analysis of CDK family genes (CDK1-8) revealed that only CDK1 was significantly upregulated in MPNST, NF, and PNF. Conclusion Increased expression of CDK1 is associated with poor prognosis in MPNST patients. Compared to other CDK family members, CDK1 exhibits a unique expression pattern, suggesting its potential as a therapeutic target for MPNST.
Objective To investigate the differences in biomechanical properties between fresh and chemically extracted acellular peri pheral nerve. Methods Thirty-six sciatic nerves were harvested from 18 adult male Wistar rats of 3 months old and randomly assigned into 3 groups (n=12 per group): normal control group (group A), the nerve segments received no treatment; Sondell method group (group B), the nerve segments were chemically extracted with the detergents of Triton X-100 and sodium deoxycholate; and improved method group (group C), chemically extracted acellular treatment of nerve was done with the detergents of Triton X-200, Sulfobetaine-10 (SB-10), and SB-16. After the acellularization, the structural changes of nerves in each group were observed by HE staining and field emission scanning electron microscope,then the biomechanical properties of nerves were tested using mechanical apparatus (Endura TEC ELF 3200). Results HE staining and field emission scanning electron microscope showed that the effect of acellularization of group C was similar to that of group B, but the effects of demyel ination and integrity of nerve fiber tube of group C were better than those of group B; the structure of broken nerves was more chaotic than before biomechanical test. The biomechanical test showed that the ultimate load, ultimate stress, ultimate strain, mechanical work to fracture in group A were the largest, the next was group C, the least was group B; the tenacity and elastic modulus in group C were the largest, the next was group B, the least was group A; but the differences were not significant (P gt; 0.05). Conclusion Compared with Sondell method, the nerve treated by improved method is more appropriate for use in vivo.
Objective
To review the research progress of graphene and its derivatives in repair of peripheral nerve defect.
Methods
The related literature of graphene and its derivatives in repair of peripheral nerve defect in recent years was extensively reviewed.
Results
It is confirmed by in vitro and in vivo experiments that graphene and its derivatives can promote cell adhesion, proliferation, differentiation and neurite growth effectively. They have good electrical conductivity, excellent mechanical properties, larger specific surface area, and other advantages when compared with traditional materials. The three-dimensional scaffold can improve the effect of nerve repair.
Conclusion
The metabolic pathways and long-term reaction of graphene and its derivatives in the body are unclear. How to regulate their biodegradation and explain the electric coupling reaction mechanism between cells and materials also need to be further explored.
Objective To explore the effect of short-term low-frequency electrical stimulation (SLES) during operation on nerve regeneration in delayed peripheral nerve injury with long gap. Methods Thirty female adult Sprague Dawley rats, weighing 160-180 g, were used to prepare 13-mm defect model by trimming the nerve stumps. Then all rats were randomly divided into 2 groups, 15 rats in each group. After nerve defect was bridged by the contralateral normal sciatic nerve, SLES was applied in the experimental group, but was not in the control group. The spinal cords and dorsal root ganglions (DRGs) were harvested to carry out immunofluorescence histochemistry double staining for growth-associated proteins 43 (GAP-43) and brain-derived neurotrophic factor (BDNF) at 1, 2, and 7 days after repair. Fluorogold (FG) retrograde tracing was performed at 3 months after repair. The mid-portion regenerated segments were harvested to perform Meyer’s trichrome staining, immunofluorescence double staining for neurofilament (NF) and soluble protein 100 (S-100) on the transversely or longitudinal sections at 3 months after repair. The segment of the distal sciatic nerve trunk was harvested for electron microscopy and morphometric analyses to measure the diameter of the myelinated axons, thickness of myelin sheaths, the G ratio, and the density of the myelinated nerve fibers. The gastrocnemius muscles of the operated sides were harvested to measure the relative wet weight ratios. Karnovsky-Root cholinesterase staining of the motor endplate was carried out. Results In the experimental group, the expressions of GAP-43 and BDNF were higher than those in the control group at 1 and 2 days after repair. The number of labeled neurons in the anterior horn of gray matter in the spinal cord and DRGs at the operated side from the experimental group was more than that from the control group. Meyer’s trichrome staining, immunofluorescence double staining, and the electron microscopy observation showed that the regenerated nerves were observed to develop better in the experimental group than the control group. The relative wet weight ratio of experimental group was significantly higher than that of the control group (t=4.633,P=0.000). The size and the shape of the motor endplates in the experimental group were better than those in the control group. Conclusion SLES can promote the regeneration ability of the short-term (1 month) delayed nerve injury with long gap to a certain extent.
Objective
To review the mechanism and effects of cell autophagy in the pathophysiology changes of peripheral nerve injury.
Methods
The recent literature about cell autophagy in peripheral nerve injury and regeneration was extensively reviewed and summarized.
Results
The researches through drugs intervention and gene knockout techniques have confirmed that the Schwann cell autophagy influences the myelin degeneration, debris clearance, inflammatory cells infiltration, and axon regeneration through JNK/c-Jun pathway. To adjust autophagy process could slow down the Wallerian degeneration, maintain the integrity of injured nerve, while the effect on axon regeneration is still controversial.
Conclusion
The Schwann cell autophagy plays a key role in the pathophysiology changes of peripheral nerve injury, the further study of its mechanism could provide new methods for the therapy of peripheral nerve injury.
ObjectiveTo summarize the research status of mandibular sensory dysfunction after transoral endoscopic thyroidectomy vestibular approach (TOETVA), and explore its potential treatment methods and existing problems, and provide ideas and methods for future clinical treatments or research. MethodThe domestic and foreign literatures about peripheral nerve injury and its treatment after TOETVA were searched and reviewed. ResultsMental nerve injury was considered to be the main cause of mandibular sensory dysfunction after TOETVA. Due to the lack of unified definitions and assessment standards, the true incidence remained unclear. In order to reduce the risk of mental nerve injury, methods such as exposing the mental nerve and combining vestibular approaches during surgery had certain advantages. In terms of treatment, several methods promoting nerve repair were noteworthy, including B vitamins, nerve growth factors, physical therapy and so on. In addition, some auxiliary treatments of Traditional Chinese Medicine also showed effectiveness in promoting nerve regeneration. ConclusionsIt is essential to avoid damage to the mental nerve and mandibular tissues during surgery. For patients with significant complaints postoperatively, active treatment should be pursued. Establishing objective and quantifiable standards for evaluating mandibular sensory dysfunction and seeking effective clinical plans through a multidisciplinary approach may be the direction for future research.
Objective To explore the clinical features, surgical treatment, and effectiveness of neurofibromas associated with neurofibromatosis type 1 (NF1). Methods A clinical data of 41 patients with NF1 admitted between December 2018 and April 2024 was retrospectively analyzed. There were 15 males and 26 females, with an average age of 27.5 years (range, 5-61 years). Only one type of neurofibroma existed in 3 patients and the rest of the patients had more than two types of neurofibromas. Fourteen patients had total resection of multiple cutaneous neurofibromas (CNF). Eighteen patients of diffuse neurofibromas underwent total, near-total, or subtotal resection. Among the 13 patients of localized nodular neurofibromas, 9 of benign tumors underwent total sub-capsular resection and 4 of malignant peripheral nerve sheath tumor (MPNST) underwent maginal resection, and only 1 underwent postoperative radiotherapy and chemotherapy. Among the 15 patients of plexiform neurofibromas (PNF), 5 patients underwent both superficial and deep PNF resection, 2 underwent the superficial PNF resection, and 8 underwent the large nodular lesions in the deep PNF resection. There were 8 MPNST, of which 7 cases underwent total sub-capsular resection and large tumor capsule resection under neurophysiological monitoring, and 1 case with the tumor located on the top of the head underwent wide resection and skin grafting. One patient underwent proton knife therapy after surgery, 2 patients did not receive radiotherapy, and the remaining patients received conventional radiotherapy. Results All patients were followed up after surgery, and the follow-up time was 3-66 months, with an average of 25.0 months. Patients with CNF recovered satisfactorily after surgery, and there was no recurrence during follow-up. Patients with diffuse neurofibromas relieved preoperative symptoms after surgery. Three patients with diffuse neurofibromas located in the head and face recurred during follow-up. The patients with benign localized nodular neurofibromas recovered well after surgery, and only 1 patient had transient regional neuralgia after surgery. Among the patients with MPNST, 2 patients died of recurrence and lung metastasis, while the remaining 2 patients had no recurrence and metastasis during follow-up. All preoperative symptoms disappeared in patients with benign PNF, and no tumor recurrence was observed during follow-up. Two patients with PNF located in the brachial plexus had difficulty in shoulder abduction after surgery, 1 patient with PNF located in vagus developed hoarseness after surgery. Among the 8 patients with MPNST in PNF, 1 died of lung metastases and 1 died of systemic failure. The remaining 6 patients were in stable condition during follow-up, and no tumor recurrence or metastasis was observed. Conclusion According to the clinical features of neurofibromas in patients with NF1, choosing appropriate surgical approaches can obtain good effectiveness. Because of the difficulty of completely resection, diffuse neurofibromas, especially those located in the head and face, are prone to recurrence after surgery. MPNST has the worst prognosis, high incidence of recurrence/metastasis, and short survival period. Total resection combined with radiotherapy can decrease local recurrence.
