Schwann Cells Of Nerves Research Articles

Phosphorylated α-Synuclein Accumulation in Schwann Cells of the Vagus Nerve Is Involved in Gastrointestinal Impairments for MPTP Mouse Model of Parkinson's Disease

Phosphorylated α-Synuclein Accumulation in Schwann Cells of the Vagus Nerve Is Involved in Gastrointestinal Impairments for MPTP Mouse Model of Parkinson's Disease

Individual mechanisms underlying peripheral nerve damage when exposed to metallic mercury

Introduction. There is a lack of knowledge of the pathophysiological mechanisms that form peripheral nerve disorders in mercury lesions of professional origin. The study aims to reveal the mechanisms underlying peripheral nerve damage in the long-term post-contact period of chronic mercury intoxication (CMI). Materials and methods. Fifty-one people had the diagnosis of a long-term period of CMI. The post-contact period was 8.5±2.6 years. The authors compared the results with a control group of 26 healthy men who had no contact with toxic substances. Stimulating electroneuromyography was performed. We studied the body systems that could contribute to the formation of disorders in the peripheral nerves. Changes in peripheral hemodynamics were studied using reovasography. The content of autoantibodies, neuron-specific enolase, serotonin, histamine, catecholamines (epinephrine, dopamine), metanephrine, and neurotrophin-3 was reviewed. The content of ceruloplasmin, secondary products of lipid peroxidation processes, reduced glutathione, the activity of superoxide dismutase and the content of nitric oxide levels were determined. Results. The study established pathogenetic structural links of peripheral nerve disorders. The autoimmune process's role was to increase the range of antibodies to the MAG protein and increase the level of antibodies to DNA. Violations of elastic-tonic properties of peripheral vessels could be associated with the functional state of motor axons. The increased content of neurotransmitters is related to the state of peripheral blood circulation; the most pronounced changes were on the legs, which could contribute to the occurrence and maintenance of vasoconstriction. The role of oxidative stress in the formation of demyelinating disorders in patients' peripheral nerves in the long-term period of CRI is possible. Conclusion. Neuroimmunological processes has an essential role in the development of peripheral nerve demyelination was shown, which consists in an increase in the content of antibodies to the MAG protein expressed on Schwann cells of peripheral nerves and in an increase in the level of antibodies to DNA involved in the formation of demyelinating changes when exposed to metallic mercury. The revealed pathological changes in the state of the peripheral blood circulation, characterized by a violation of the vessels' elastic-tonic properties, leading to demyelination of motor axons in patients in the long-term period of CMI. The increased content of neurotransmitters in the examined is of great importance in the state of peripheral circulation. Pronounced changes in blood circulation are established on the lower extremities, which may be associated with the predominance of α-adrenergic receptors in the arterial bed and may contribute to the occurrence and maintenance of vasoconstriction in the legs. The relationship between changes in indicators of oxidative stress, consisting of a decrease in the value of superoxide dismutase and reduced glutathione, and the formation of demyelinating disorders of peripheral nerves in patients in the long-term period of CMI has been proved.

Blood-Nerve Barrier (BNB) Pathology in Diabetic Peripheral Neuropathy and In Vitro Human BNB Model.

In diabetic peripheral neuropathy (DPN), metabolic disorder by hyperglycemia progresses in peripheral nerves. In addition to the direct damage to peripheral neural axons, the homeostatic mechanism of peripheral nerves is disrupted by dysfunction of the blood–nerve barrier (BNB) and Schwann cells. The disruption of the BNB, which is a crucial factor in DPN development and exacerbation, causes axonal degeneration via various pathways. Although many reports revealed that hyperglycemia and other important factors, such as dyslipidemia-induced dysfunction of Schwann cells, contributed to DPN, the molecular mechanisms underlying BNB disruption have not been sufficiently elucidated, mainly because of the lack of in vitro studies owing to difficulties in establishing human cell lines from vascular endothelial cells and pericytes that form the BNB. We have developed, for the first time, temperature-sensitive immortalized cell lines of vascular endothelial cells and pericytes originating from the BNB of human sciatic nerves, and we have elucidated the disruption to the BNB mainly in response to advanced glycation end products in DPN. Recently, we succeeded in developing an in vitro BNB model to reflect the anatomical characteristics of the BNB using cell sheet engineering, and we established immortalized cell lines originating from the human BNB. In this article, we review the pathologic evidence of the pathology of DPN in terms of BNB disruption, and we introduce the current in vitro BNB models.

Schwannoma of the infratemporal fossa - A rare case report

Schwannoma is a benign nerve sheath tumour that originates from schwann cells of the peripheral nerve. In spite of constituting 25-40% of head and neck tumours its in-traoral presentation is rare which accounts for only 1%. The purpose of this case report is to highlight the rarity of this lesion, to emphasize the significance of an accurate diagnosis and to include tumours of nerve sheath origin in the differential diagnosis of facial asymmetry.

A preliminary observational study on the vascular, nerve, and lymphatic anatomy and histology of the labia minora from cadaveric and surgical samples.

To better understand details of the fine anatomy of the labia minora, present images of the vascular anatomy and characterize the nerve and lymphatic distribution of the labia minora. Two fixed and five fresh cadaveric specimens were perfused and dissected, and the vascular network was photographed. Labia minora samples, prepared from cadavers, and tissue resulting from labia reduction surgery underwent hematoxylin and eosin staining and S100 and D2-40 immunohistochemical staining. Arteries emanated from the base to the edge of the labia minora, where there was a larger feeding artery, and the arteries were anastomosed. The veins formed anastomotic branches in the same direction as the edge of the labia minora. Arteries and veins that accessed the labia minora were successfully perfused at the same time with no obvious association. Sensory nerve endings were abundant, mostly larger with myelinated nerve trunks and Schwann cells in the central area with suggested neurovascular associations and smaller with no obvious aggregation at the edge. The medial area had 23.63 ± 11.82 nerves/view, the lateral area 21.30 ± 11.49 nerves/view (P > 0.05). The thickest nerve bundle was 3.16 ± 1.41mm from the medial epidermis and 3.13 ± 1.47mm from the lateral epidermis. Lymphatic vessels showed no obvious regional distribution. Labia minora were 21.77 ± 5.69mm wide with 252.87 ± 63.01 lymphatic vessels at 3.67 ± 1.61/mm2 density. The shortest inner diameter of dilated lymphatic vessels was 161.09 ± 49.99 μm. A larger feeding artery exists in the labia minora, which should be noticed in the pre-surgery design of labiaplasty. No difference was observed in the nerve distribution between the medial and lateral sides. Lymphedema might not be the cause of labial hypertrophy.

Application of bioactive hydrogels combined with dental pulp stem cells for the repair of large gap peripheral nerve injuries

Due to the limitations in autogenous nerve grafting or Schwann cell transplantation, large gap peripheral nerve injuries require a bridging strategy supported by nerve conduit. Cell based therapies provide a novel treatment for peripheral nerve injuries. In this study, we first experimented an optimal scaffold material synthesis protocol, from where we selected the 10% GFD formula (10% GelMA hydrogel, recombinant human basic fibroblast growth factor and dental pulp stem cells (DPSCs)) to fill a cellulose/soy protein isolate composite membrane (CSM) tube to construct a third generation of nerve regeneration conduit, CSM-GFD. Then this CSM-GFD conduit was applied to repair a 15-mm long defect of sciatic nerve in a rat model. After 12 week post implant surgery, at histologic level, we found CSM-GFD conduit could regenerate nerve tissue like neuron and Schwann like nerve cells and myelinated nerve fibers. At physical level, CSM-GFD achieved functional recovery assessed by a sciatic functional index study. In both levels, CSM-GFD performed like what gold standard, the nerve autograft, could do. Further, we unveiled that almost all newly formed nerve tissue at defect site was originated from the direct differentiation of exogeneous DPSCs in CSM-GFD. In conclusion, we claimed that this third-generation nerve regeneration conduit, CSM-GFD, could be a promising tissue engineering approach to replace the conventional nerve autograft to treat the large gap defect in peripheral nerve injuries.

FGF5 Regulates Schwann Cell Migration and Adhesion.

The fibroblast growth factor (FGF) family polypeptides play key roles in promoting tissue regeneration and repair. FGF5 is strongly up-regulated in Schwann cells of the peripheral nervous system following injury; however, a role for FGF5 in peripheral nerve regeneration has not been shown up to now. In this report, we examined the expression of FGF5 and its receptors FGFR1-4 in Schwann cells of the mouse sciatic nerve following injury, and then measured the effects of FGF5 treatment upon cultured primary rat Schwann cells. By microarray and mRNA sequencing data analysis, RT-PCR, qPCR, western blotting and immunostaining, we show that FGF5 is highly up-regulated in Schwann cells of the mouse distal sciatic nerve following injury, and FGFR1 and FGFR2 are highly expressed in Schwann cells of the peripheral nerve both before and following injury. Using cultured primary rat Schwann cells, we show that FGF5 inhibits ERK1/2 MAP kinase activity but promotes rapid Schwann cell migration and adhesion via the upregulation of N-cadherin. Thus, FGF5 is an autocrine regulator of Schwann cells to regulate Schwann cell migration and adhesion.

Progress in the surgical treatment of trigeminal schwannoma

Trigeminal schwannomas(TSs) is the second most common intracranial schwannomas next to acoustic neuroma. These uncommon, slow-growing tumors, which prove to originated from Schwann cells of the fifth brain nerve, can achieve their development into various compartments.Previous to the era of microsurgery, the total tumor resection rate was low, and the postoperative neurological function was seriously damaged.With the development of microsurgery and skull base approach, the microsurgery effect of TSs has been improved. Besides, neuroendoscopy is also used in the operation of some types of trigeminal schwannomas. Radiation therapy can be performed to control tumor growth for the patients who cannot tolerate surgery, have small tumor volume, have residual tumor tissue or relapse.

Head-Neck Schwannoma: Presenting as a Huge Posterior Neck Swelling

Schwannomas are benign slow growing tumors that arise from the Schwann cells of nerve, also called neurilemmoma. Head and Neck schwannomas usually present as solitary with well demarcated lesions. These tumors usually remain asymptomatic but present as slowly enlarging neck masses. Its origin is only determined during surgical procedure along the course and distribution of the nerve. Preoperative diagnosis is usually made by physical examination and aided by ultrasonography, magnetic resonance imaging or computed tomography and fine needle aspiration cytology but open biopsy is not recommended. The main stay of treatment is complete intracapsular excision with preserving the nerve of origin.

Pre-clinical evaluation of new dibucaine formulations for preventive analgesia

We have previously developed ammonium sulphate gradient loaded liposomes to encapsulate dibucaine. Thus, the purpose of this study was to evaluate the pre-clinical safety and effectiveness of this novel ionic liposomal formulation of dibucaine (DBC), as described in previous work. Effectiveness was evaluated in vivo on Wistar rats (n = 8) that received plain DBC or liposomal DBC (DBCLUV). Control empty liposomes (without DBC) or saline were also used as control. Sciatic nerve block was performed using the formulations or controls (0.4 mL). A hindpaw incision-based postoperative pain model was used to evaluate mechanical hypersensitivity with von Frey filaments. To verify antiinflamatory activity protein levels of TNF-α, IL-1β, substance P and CGRP were measured by ELISA in the hindpaw tissue after 1 and 6 hours of the incision. To corroborate drug safety, sciatic nerve Schwann cell cultures were treated with the aforementioned formulations and assessed for cell viability (MTT assay) and death (flow cytometry assay). Histopathology of the tissues surrounding the sciatic nerve region was also assessed 2 and 7 days after treatment. All animals presented post incisional hypersensitivity and DBCLUV showed longer analgesic effect (p < 0.001). DBCLUV reduced TNF-α and CGRP levels (p < 0.05). Histopathological evaluation showed greater inflammatory reaction after the administration of control liposomes when compared to DBC (p < 0.05). There was no difference in Schwann cell viability and death between plain and encapsulated DBC. DBCLUV was safe and enhanced anaesthesia duration due to slow release of dibucaine from ammonium sulphate gradient loaded liposomes.

Exosomes derived from differentiated Schwann cells inhibit Schwann cell migration via microRNAs.

Exosomes derived from Schwann cells have been known to have a variety of functions in the development and repair of the peripheral nervous system, and cyclic AMP (cAMP) is a key inducer of Schwann cell differentiation. In the present study, we aimed to study the effect of exosomes derived from differentiated Schwann cells on the expression of microRNAs (miRNAs). To show that miRNAs were altered from exosomes derived from Schwann cells, we conducted next-generation sequencing (NGS) arrays with exosomes derived from cAMP-induced differentiated Schwann cells and control. NGS arrays revealed that 22 miRNAs, 33 small nucleolar RNAs, one antisense RNA, and two mRNAs were upregulated, while 37 mRNAs, one tRNA, and 35 antisense RNAs were downregulated. We also confirmed that miRNA211 and miR92a-3p were upregulated, while the expression levels of hypoxia-inducible factor, rat cyclin-dependent kinase 2, and rat platelet-derived growth factor C were reduced in exosomes derived from cAMP-induced differentiated Schwann cells. Venn diagrams were used to identify overlapping miRNA targets from highly expressed miRNAs (miR211-5p, miR211-3p, and miR92a-3p). The pathways identified via Kyoto Encyclopedia of Genes and Genomes analysis of the target genes are associated with nerve regeneration and Schwann cell proliferation such as the tumor necrosis factor signaling pathway, dopaminergic synapse, and neurotrophin signaling, and cAMP-dependent signaling pathways. Additionally, we observed that exosomes derived from differentiated Schwann cells suppressed Schwann cell migration, while control exosomes obtained from undifferentiated Schwann cells did not. Together, the results suggested that exosomes released from differentiated Schwann cells regulated Schwann cell migration through changes in miRNA expression.

Human adipose-derived mesenchymal stem cell-conditioned medium ameliorates polyneuropathy and foot ulceration in diabetic BKS db/db mice

BackgroundDiabetic polyneuropathy (DPN) is the most common and early developing complication of diabetes mellitus, and the key contributor for foot ulcers development, with no specific therapies available.Different studies have shown that mesenchymal stem cell (MSC) administration is able to ameliorate DPN; however, limited cell survival and safety reasons hinder its transfer from bench to bedside. MSCs secrete a broad range of antioxidant, neuroprotective, angiogenic, and immunomodulatory factors (known as conditioned medium), which are all decreased in the peripheral nerves of diabetic patients. Furthermore, the abundance of these factors can be boosted in vitro by incubating MSCs with a preconditioning stimulus, enhancing their therapeutic efficacy. We hypothesize that systemic administration of conditioned medium derived from preconditioned MSCs could reverse DPN and prevent foot ulcer formation in a mouse model of type II diabetes mellitus.MethodsDiabetic BKS db/db mice were treated with systemic administration of conditioned medium derived from preconditioned human MSCs; conditioned medium derived from non-preconditioned MSCs or vehicle after behavioral signs of DPN was already present. Conditioned medium or vehicle administration was repeated every 2 weeks for a total of four administrations, and several functional and structural parameters characteristic of DPN were evaluated. Finally, a wound was made in the dorsal surface of both feet, and the kinetics of wound closure, re-epithelialization, angiogenesis, and cell proliferation were evaluated.ResultsOur molecular, electrophysiological, and histological analysis demonstrated that the administration of conditioned medium derived from non-preconditioned MSCs or from preconditioned MSCs to diabetic BKS db/db mice strongly reverts the established DPN, improving thermal and mechanical sensitivity, restoring intraepidermal nerve fiber density, reducing neuron and Schwann cell apoptosis, improving angiogenesis, and reducing chronic inflammation of peripheral nerves. Furthermore, DPN reversion induced by conditioned medium administration enhances the wound healing process by accelerating wound closure, improving the re-epithelialization of the injured skin and increasing blood vessels in the wound bed in a skin injury model that mimics a foot ulcer.ConclusionsStudies conducted indicate that MSC-conditioned medium administration could be a novel cell-free therapeutic approach to reverse the initial stages of DPN, avoiding the risk of lower limb amputation triggered by foot ulcer formation and accelerating the wound healing process in case it occurs.

Granular Cell Tumor of Breast: Rare Tumor Masquerading as Malignancy

Granular cell tumor (GCT) is a rare soft tissue tumor that arises from the Schwann cells of peripheral nerves. It was first postulated by Abrikossoff in 1926 as Myoblastoma. About 5-15% of these tumors occur in the breast and less than 1% has the potential to be malignant. Here we present a case of 41 years old premenopausal woman with Benign GCT of the right breast, having clinically malignant features. The clinical and radiological features of GCT are similar to malignant lump. However, histology showing presence of sheets of polygonal cells with abundant granular eosinophilic cytoplasm with round nuclei and granules with Periodic acid–Schiff (PAS) positive, diastase resistant and S-100 antigen positive are confirmatory. Treatment of Granular cell tumor is wide local excision. There is apparently no role of chemotherapy and radiotherapy. The presence of GCT in the breast is quite rare and clinically as well as radiologically it may mimic malignancy, however with histopathology and appropriate immunohistochemistry, proper diagnosis can be made.

Granular Cell Tumor of Breast: Rare Tumor Masquerading as Malignancy

Granular cell tumor (GCT) is a rare soft tissue tumor that arises from the Schwann cells of peripheral nerves. It was first postulated by Abrikossoff in 1926 as Myoblastoma. About 5-15% of these tumors occur in the breast and less than 1% has the potential to be malignant. Here we present a case of 41 years old premenopausal woman with Benign GCT of the right breast, having clinically malignant features. The clinical and radiological features of GCT are similar to malignant lump. However, histology showing presence of sheets of polygonal cells with abundant granular eosinophilic cytoplasm with round nuclei and granules with Periodic acid–Schiff (PAS) positive, diastase resistant and S-100 antigen positive are confirmatory. Treatment of Granular cell tumor is wide local excision. There is apparently no role of chemotherapy and radiotherapy. The presence of GCT in the breast is quite rare and clinically as well as radiologically it may mimic malignancy, however with histopathology and appropriate immunohistochemistry, proper diagnosis can be made.

Clinical outcomes of resecting scarpa's ganglion during vestibular schwannoma surgery

Vestibular schwannomas are slow-growing tumors arising from the Schwann cells of the vestibular nerve. Scarpa’s ganglion, the vestibular nerve ganglion, is located within the internal auditory meatus. Surgical treatment of vestibular schwannomas carries the potential of resecting Scarpa’s ganglion along with the tumor. No prior studies have evaluated outcomes based on the presence of Scarpa’s ganglion within tumor specimens. The neurosurgery patient records were queried for patients who underwent surgical resection of vestibular schwannomas at the University of Missouri Healthcare between January 1, 2008 and December 31, 2018. Inclusion criteria consisted of minimum age of 18, imaging demonstrating an eighth nerve tumor, surgical resection thereof, and a final pathological diagnosis of WHO grade I schwannoma. Data were collected retrospectively. The histological slides of the tumors were reviewed, and the presence or absence of the ganglion was noted. Outcomes analyzed included postoperative dizziness, hearing, and facial nerve function. Fifty-two patients met inclusion criteria. Ten (19%) resected tumors contained portions of the ganglion. No difference in risk of resection of ganglion occurred based on the surgical approach (p = 0.2454). Mean follow-up duration was 24.6 months ± 26.2 standard deviation. No differences in postoperative hearing or dizziness (p = 0.8483 and p = 0.3190 respectively) were present if Scarpa’s ganglion was resected. House-Brackmann classification of facial nerve function at last follow-up was similar (p = 0.9190). Resection of Scarpa’s ganglion with vestibular schwannomas does not increase risk of post-operative dizziness, facial nerve weakness, or hearing loss.

Evaluation of the Antioxidant and Anti‐inflammatory Effects of SMTP‐44D against Streptozotocin‐Induced Diabetic Neuropathy in Mice

ObjectiveDiabetic neuropathy (DN), a major complication of diabetic mellitus, is present in more than 50% of diabetic patients. During the early stages of pathologic progression, patients with DN may experience sensory defects such as allodynia and hyperalgesia. Patients in advanced stages may present with sensory paralysis, such as nerve injury and the degeneration of axons, which are frequently accompanied by foot ulcerations, amputations, and poor prognoses. The pathogenesis of DN primarily involves oxidative stress and inflammation; thus, oxidative stress and inflammation are considered important therapeutic targets. However, few effective therapies are approved for the treatment of painful or insensate DN. The study aimed to evaluate the antioxidant and anti‐inflammatory effects of Stachybotrys microspora triprenyl phenol‐44D (SMTP‐44D) in a mouse model of DN.MethodsWe induced diabetes in C57BL/6J male mice by administering a single intraperitoneal injection of streptozotocin (200 mg/kg). SMTP‐44D (0.3, 3, and 30 mg/kg) was subsequently administered daily from 1 to 4 weeks after the injection of streptozotocin. The effects of SMTP‐44D were evaluated by mechanical and thermal thresholds to assess allodynia and hyperalgesia, and conduction velocity and blood flow in sciatic nerves. In addition, the levels of oxidative stress and inflammatory cytokines in sciatic nerves were determined via a thiobarbituric acid reactive substances assay and enzyme‐linked immunosorbent assay, respectively. To evaluate for neurological degeneration, G‐ratios (ratio of axon diameter to myelinated fiber diameter) and myelin thickness in the Schwann cells of sciatic nerves were measured.ResultsMechanical and thermal thresholds, conduction velocity, blood flow, and myelin thickness were significantly lower in the diabetic group than in the nondiabetic group. Moreover, the levels of oxidative stress (e.g., malondialdehyde), inflammatory cytokines (e.g., tumor necrosis factor‐α, interleukin‐1β, and interleukin‐6), and G‐ratios were significantly higher in the diabetic group than in the nondiabetic group. Such results demonstrated that the DN model was successfully established. In mice with DN, treatment with SMTP‐44D significantly and dose‐dependently improved allodynia, hyperalgesia, conduction velocity of sciatic nerves, and blood flow in sciatic nerves. Furthermore, G‐ratios and myelin thickness in the Schwann cells of sciatic nerves were also significantly improved by the suppression of oxidative stress and inflammatory cytokines.ConclusionIt is believed that oxidative stress and inflammation are involved in the pathological progression of DN and that they are important therapeutic targets. Our results showed that SMTP‐44D improved DN by exerting antioxidant and anti‐inflammatory effects, which suggests that SMTP‐44D is a potential novel therapeutic agent for the treatment of DN.Support or Funding InformationThis study was supported in part by the Japan Society for the Promotion of Science KAKENHI (Grant Number 26460346, awarded to KN; Grant Number 18K14958, awarded to KS). SMTP‐44D was generously donated by TMS Co., Ltd. (Tokyo, Japan).

Gli3 is a Key Factor in the Schwann Cells from Both Intact and Injured Peripheral Nerves

Hedgehog (Hh) signaling has been shown to be involved in regulating both intact and injured peripheral nerves. Therefore, it is critical to understand how Hh signaling is regulated in the peripheral nerve. One of the transcription factors of the Hh signaling pathway, Gli3, functions as both a repressor and an activator of Hh signaling activity. However, it remains unclear whether Gli3 is involved in controlling the intact and/or injured peripheral nerves. We found that Gli3 act as a repressor in the Schwann cells (SCs) of intact sciatic nerves. Although Dhh and Ptch1 expression were present, Hh signaling was not activated in these SCs. Moreover, heterozygous Gli3 mutation (Gli3−/+) induced ectopic Hh signaling activity in SCs. Hh signaling was thus suppressed by Gli3 in the SCs of intact sciatic nerves. Minor morphological changes were observed in the intact nerves from Gli3−/+ mice. Gli3 expression was significantly decreased following injury and ligand expression switched from Dhh to Shh, which activated Hh signaling in SCs from wild-type mice. Changes of these ligands was found to be important for nerve regeneration in which the downregulation of Gli3 was also involved. In fact, Gli3−/+ mice exhibited accelerated ligand switching and subsequent nerve regeneration. Both suppression of Hh signaling with Gli3 in the intact nerves and activation of Hh signaling without Gli3 in the injured nerve were observed in the SCs in an autocrine manner. Thus, Gli3 is a key factor in the control of intact peripheral nerve homeostasis and nerve regeneration.

Salidroside promotes sciatic nerve regeneration following combined application epimysium conduit and Schwann cells in rats.

Schwann cell and nerve conduit are crucial for nerve regeneration and re-myelination after peripheral nerves injury. To investigate the effects of Salidroside on autogenous epimysium conduit mixed with BD matrigel and RSC96 Schwann cells on an animal model with 5 mm sciatic nerve defect injury in rat, motor function, muscle reinnervation, immunohistochemical staining, retrograded tracing and Western blot were used in this study. The results showed that Salidroside enhanced the compound effects of epimysium conduit mixed with BD matrigel and RSC96 Schwann cells to improve the sciatic functional index and the gastrocnemius muscle weight ratio, which were better than EPM group at 8 weeks and 12 weeks post operation. Immunofluorescence and Western blot results of P75NTRshowed that Salidroside improved the sciatic nerve regeneration, and retrograded tracing of CTB-Alexa 488 also supported that Salidroside was better to promote CTB tracer transporting from the distal nerve defect to the ipsilateral dorsal root ganglion and ventral horn of L3-L5 spinal cord on post-operation 8 weeks and 12 weeks. Our results demonstrated that Salidroside improved the effect of autogenous epimysium conduit mixed with BD matrigel and RSC96 Schwann cells on sciatic nerve regeneration in our study.Impact statementPeripheral nerve injury and regeneration remain a major challenge. Although nerve conduit and Schwann cells have been used to study the nerve regeneration, our results demonstrated that Salidroside improved the regenerative effect in a rat model with sciatic nerve injury model, following a combined application of autogenous epimysium conduit mixed with Schwann cells. Different concentrations of Salidroside combining autogenous epimysium conduit and Schwann cells were applied to compare the epimysium conduit group and the epimysium conduit combining Schwann cells group. Based on the results of motor function and muscle reinnervation evaluation, as well as neuronal tracing and expression of P75NTR, our study for the first time suggests that Salidroside may improve the regeneration effect on the sciatic nerve following a combined application of epimysium conduit and RSC96 Schwann cells in rats.

The significance of solute carrier group of genes in the pathogenesis and treatment of diabetic microvascular complications

Aim- To study the impact of the solute carrier group of genes on the mechanisms involved in hyperglycemia induced tissue damage and its implication on the treatment of diabetic microvascular complications.Introduction – the estimated figure of people suffering from diabetes worldwide in 2019 was 9.3% (463 million people) and the projected estimates for 2030 is an alarming figure of approximately 578 million people [1]. Various pathological processes are responsible for the development of diabetes, the irreversible factor is the destruction of β-cells in the pancreas leading to insulin insufficiency, or other factors such as obesity and abnormal carbohydrate and fat metabolism which leads to insulin resistance and diminished tissue response to insulin. Defects in insulin secretion and insulin action frequently coexist in diabetics [2].The damaging effects of hyperglycemia are classified into microvascular complications - diabetic retinopathy, neuropathy and nephropathy, and macrovascular complications - coronary artery disease, peripheral artery disease and stroke [3]. The effects of hyperglycemia are not seen in all cells of the body, but are distinct only in certain types of cells: neurons and Schwann cells in peripheral nerves, capillary endothelial cells, mesengeal cells in the renal glomerulus due to their inability to effectively maintain a constant level of glucose, in contrast most cells are able to reduce the transport of glucose when exposed to hyperglycemia [4, 5, 6].

Effects of 2, 5-hexanedione on S100β of Schwann cells in rat sciatic nerves

To investigate the expression of S100β protein and mRNA of Schwann cells(SC) in sciatic nerves of 2, 5-hexanedione(HD) intoxicated rats. Nine-week old SPF male Wistar rats were administered at daily dosing of 100 and 300 mg/kg by intraperitoneal injection for continuous 8 weeks(five times every week). Age-matched control rats received an equivalent volume of normal saline. Ten rats in each group were sacrificed and sciatic nerves were excised for S100β determination, with excised sciatic nerves from another three rats for morphological observation through electron microscope. At the end of the exposure, the other 8-week treated animals were allowed to naturally recover for 8 weeks and sciatic nerves were excised at the end of the test. S100β protein contents were determined by immunohistochemistry method, and mRNA expression was observed by real-time quantitative polymerase chain reaction(PCR). HD intoxication with 300 mg/kg was associated with severe neurological deficits of paralysis in hindlimbs, accompanied with evident movement gait abnormalities for 100 mg/kg dosage. The morphological abnormalities in myelin sheath of sciatic nerves were observed through electron microscope after HD-exposure. The S100β contents in 100 mg/kg and 300 mg/kg groups remained relatively unaffected with 92% and 79% of the control respectively after HD-intoxication, and a increase to 149%(P&lt;0. 05) and 119% after a recovery of 8 weeks was accompanied with. As to S100β mRNA, HD-intoxication was associated with decreased expression to 0. 65(P&lt;0. 05) and 0. 56 times(P&lt;0. 05) of the control, and 1. 46 and 0. 87 times for 8-week recovery individually. The S100β protein and mRNA levels were influenced by HD exposure, and the result suggested that S100β might be involved in HD-induced peripheral axonopathy.