Schwann Cell Remyelination Research Articles

Multilevel neurium-mimetic individualized graft via additive manufacturing for efficient tissue repair

Complicated peripheral nerve injuries or defects, especially at branching sites, remain a prominent clinical challenge after the application of different treatment strategies. Current nerve grafts fail to match the expected shape and size for delicate and precise branched nerve repair on a case-by-case basis, and there is a lack of geometrical and microscale regenerative navigation. In this study, we develop a sugar painting-inspired individualized multilevel epi-/peri-/endoneurium-mimetic device (SpinMed) to customize natural cues, featuring a selectively protective outer sheath and an instructive core, to support rapid vascular reconstruction and consequent efficient neurite extension along the defect area. The biomimetic perineurium dictates host-guest crosslinking in which new vessels secrete multimerin 1 binding to the fibroin filler surface as an anchor, contributing to the biological endoneurium that promotes Schwann cell homing and remyelination. SpinMed implantation into rat sciatic nerve defects yields a satisfactory outcome in terms of structural reconstruction, with sensory and locomotive function restoration. We further customize SpinMed grafts based on anatomy and digital imaging, achieving rapid repair of the nerve trunk and branches superior to that achieved by autografts and decellularized grafts in a specific beagle nerve defect model, with reliable biosafety. Overall, this intelligent art-inspired biomimetic design offers a facile way to customize sophisticated high-performance nerve grafts and holds great potential for application in translational regenerative medicine.

Runx2 regulates peripheral nerve regeneration to promote Schwann cell migration and re-myelination.

Abstract JOURNAL/nrgr/04.03/01300535-202407000-00038/figure1/v/2023-11-20T171125Z/r/image-tiff Runx2 is a major regulator of osteoblast differentiation and function; however, the role of Runx2 in peripheral nerve repair is unclear. Here, we analyzed Runx2 expression following injury and found that it was specifically up-regulated in Schwann cells. Furthermore, using Schwann cell-specific Runx2 knockout mice, we studied peripheral nerve development and regeneration and found that multiple steps in the regeneration process following sciatic nerve injury were Runx2-dependent. Changes observed in Runx2 knockout mice include increased proliferation of Schwann cells, impaired Schwann cell migration and axonal regrowth, reduced re-myelination of axons, and a block in macrophage clearance in the late stage of regeneration. Taken together, our findings indicate that Runx2 is a key regulator of Schwann cell plasticity, and therefore peripheral nerve repair. Thus, our study shows that Runx2 plays a major role in Schwann cell migration, re-myelination, and peripheral nerve functional recovery following injury.

The therapeutic effects of transferring remote ischemic preconditioning serum in rats with neuropathic pain symptoms

Background and objectivesNeuropathic pain is defined as pain caused by damage to the nerve as a result of a lesion or disease. It has been shown that ischemic preconditioning exerts a protective role in various tissue injuries; however, the effect of transplantation of remote ischemic preconditioning serum (RIPCs) on neuropathic pain symptoms has not been studied. The aim of this project is to investigate the effect of RIPCs transfusion by different routes of administration on neuropathic pain symptoms. Our secondary aim was to demonstrate the role of Schwann cells in the regeneration of sciatic nerve injury and to evaluate the change in the number of glial cells in the spinal cord dorsal horn. MethodsThe sciatic nerve partial ligation method was used to induce neuropathic pain. Changes in neuropathic pain symptoms were assessed by measuring thermal hyperalgesia and mechanical allodynia. To determine the possible therapeutic site, alterations in the number of spinal cord lumbar posterior horn microglia and astrocytes were evaluated by ionized calcium-binding adapter molecule 1 (iba1) and glial fibrillary acidic protein (GFAP) immunostaining. Myelin basic protein immunohistochemistry was also used to assess Schwann cell immunoreactivity in the sciatic nerve. ResultsIn rats that underwent partial sciatic nerve ligation, neuropathic pain symptoms developed on average on day 12 and persisted up to day 21 (p < 0.0001). RIPCs administered intravenously for five days reduced thermal hyperalgesia more than intraperitoneal and subcutaneous administration (p < 0.05). Both central glial cells appear to play a role in the effect of RIPCs. RIPCs treatment increases Schwann cell remyelination. ConclusionsOur results showed that intravenously administered RIPCs remarkably improved the neuropathic pain symptoms, thermal hyperalgesia and mechanical allodynia. Further studies are needed to evaluate the role of RIPCs transfusion on glial cells.

Metformin promotes Schwann cell remyelination, preserves neural tissue and improves functional recovery after spinal cord injury

Patients with a spinal cord injury (SCI) usually suffer lifelong disability as a result. Considering this, SCI treatment and pathology study are urgently needed. Metformin, a widely used hypoglycemic drug, has been indicated for its important role in central nervous system diseases. This study aimed to investigate the potential effect of metformin on remyelination after SCI. In the present study, we established a cervical contusion SCI model and metformin treatment was applied after SCI. Biomechanical parameters and behavioral assessment were used to evaluate the severity of injury and the improvement of functional recovery after SCI, respectively. The immunofluorescence and western blot were performed at the terminal time point. Our results showed that treating with metformin after SCI improved functional recovery by reducing the white matter loss and promoting Schwann cell remyelination, and the Nrg1/ErbB signaling pathway may be involved in promoting remyelination mediated by oligodendrocytes and Schwann cells. In addition, the area of spared tissues was significantly increased in the metformin group. However, metformin had no significant effects on the glial scar and inflammation after SCI. In summary, these findings indicated that the role of metformin in Schwann cell remyelination after SCI was probably related to the regulation of the Nrg1/ErbB pathway. It is, therefore, possible to suggest that metformin may be a potential therapy for SCI.

Neuritin Promotes Bone Marrow-Derived Mesenchymal Stem Cell Migration to Treat Diabetic Peripheral Neuropathy.

The purpose of this study is to explore the effect and mechanism of neuritin overexpression in the bone marrow on peripheral neuropathy in type 2 diabetic (db/db) mice. We analyzed the impact of bone marrow neuritin overexpression on diabetic peripheral neuropathy and migration of bone marrow mesenchymal stem cells in db/db mice. Antagonists were used to inhibit the stromal cell-derived factor (SDF)-1α/C-X-C chemokine receptor type 4 (CXCR4)-phosphoinositide 3-kinase (PI3K)/Akt signaling pathway in primary cultured bone marrow mesenchymal stem cells. Immunofluorescence, transmission electron microscopy, Oil Red O staining, and transwell migration assays were used. Bone marrow-specific overexpression of neuritin in db/db mice was successfully established. Overexpression of neuritin in the bone marrow ameliorated hyperglycemia, prevented diabetic peripheral neuropathy, protected the ultrastructure of the sciatic nerve and intra-epidermal nerve fiber density, and promoted Schwann cell proliferation and remyelination in the sciatic nerve. Moreover, it ameliorated fat accumulation, adipocyte number, and vascular and nerve densities; decreased glutamate content in serum and bone marrow; restored gradient SDF-1α contents between bone marrow, blood, and sciatic nerve; and promoted impaired diabetic bone marrow mesenchymal stem cell migration. Neuritin improves bone marrow mesenchymal stem cell migration via the SDF-1α/CXCR4-PI3K/Akt signaling pathway in vitro. Overexpression of neuritin in the bone marrow can locally ameliorate neuropathy in the bone marrow. This improves the migration capability of bone marrow mesenchymal stem cells and repairs diabetic peripheral neuropathy, at least partly by activating the PI3K/Akt pathway through the SDF-1α/CXCR4 axis.

Theophylline Induces Remyelination and Functional Recovery in a Mouse Model of Peripheral Neuropathy.

Charcot-Marie-Tooth disease (CMT) is a large group of inherited peripheral neuropathies that are primarily due to demyelination and/or axonal degeneration. CMT type 1A (CMT1A), which is caused by the duplication of the peripheral myelin protein 22 (PMP22) gene, is a demyelinating and the most frequent CMT subtype. Hypermyelination, demyelination, and secondary loss of large-caliber axons are hallmarks of CMT1A, and there is currently no cure and no efficient treatment to alleviate the symptoms of the disease. We previously showed that histone deacetylases 1 and 2 (HDAC1/2) are critical for Schwann cell developmental myelination and remyelination after a sciatic nerve crush lesion. We also demonstrated that a short-term treatment with Theophylline, which is a potent activator of HDAC2, enhances remyelination and functional recovery after a sciatic nerve crush lesion in mice. In the present study, we tested whether Theophylline treatment could also lead to (re)myelination in a PMP22-overexpressing mouse line (C22) modeling CMT1A. Indeed, we show here that a short-term treatment with Theophylline in C22 mice increases the percentage of myelinated large-caliber axons and the expression of the major peripheral myelin protein P0 and induces functional recovery. This pilot study suggests that Theophylline treatment could be beneficial to promote myelination and thereby prevent axonal degeneration and enhance functional recovery in CMT1A patients.

Schwann cell remyelination of the central nervous system: why does it happen and what are the benefits?

Myelin sheaths, by supporting axonal integrity and allowing rapid saltatory impulse conduction, are of fundamental importance for neuronal function. In response to demyelinating injuries in the central nervous system (CNS), oligodendrocyte progenitor cells (OPCs) migrate to the lesion area, proliferate and differentiate into new oligodendrocytes that make new myelin sheaths. This process is termed remyelination. Under specific conditions, demyelinated axons in the CNS can also be remyelinated by Schwann cells (SCs), the myelinating cell of the peripheral nervous system. OPCs can be a major source of these CNS-resident SCs—a surprising finding given the distinct embryonic origins, and physiological compartmentalization of the peripheral and central nervous system. Although the mechanisms and cues governing OPC-to-SC differentiation remain largely undiscovered, it might nevertheless be an attractive target for promoting endogenous remyelination. This article will (i) review current knowledge on the origins of SCs in the CNS, with a particular focus on OPC to SC differentiation, (ii) discuss the necessary criteria for SC myelination in the CNS and (iii) highlight the potential of using SCs for myelin regeneration in the CNS.

Functional recovery with histomorphometric analysis of nerves and muscles after combination treatment with erythropoietin and dexamethasone in acute peripheral nerve injury.

IntroductionPeripheral nerve injury (PNI) often leads to significant functional loss in patients and poses a challenge to physicians since treatment options for improving functional outcomes are limited. Recent studies suggest that erythropoietin and glucocoticoids have beneficial effects as mediators of neuro-regenerative processes. We hypothesized that combination treatment with erythropoietin and glucocoticoids would have a synergistic effect on functional outcome after PNI.Materials and methodsSciatic nerve crush injury was simulated in ten-week-old male C57BL/6 mice. The mice were divided into four groups according to the type of drugs administered (control, erythropoietin, dexamethasone, and erythropoietin with dexamethasone). Motor functional recovery was monitored by walking track analysis at serial time points up to 28 days after injury. Morphological analysis of the nerve was performed by immunofluorescent staining for neurofilament (NF) heavy chain and myelin protein zero (P0) in cross-sectional and whole-mount nerve preparations. Additionally, morphological analysis of the muscle was performed by Hematoxylin and eosin staining.ResultsCombination treatment with erythropoietin and dexamethasone significantly improved the sciatic functional index at 3, 7, 14, and 28 days after injury. Fluorescence microscopy of cross sectional nerve revealed that the combination treatment increased the ratio of P0/NF-expressing axons. Furthermore, confocal microscopy of the whole-mount nerve revealed that the combination treatment increased the fluorescence intensity of P0 expression. The cross-sectional area and minimum Feret’s diameter of the muscle fibers were significantly larger in the mice which received combination treatment than those in the controls.ConclusionOur results demonstrated that combination treatment with erythropoietin and dexamethasone accelerates functional recovery and reduces neurogenic muscle atrophy caused by PNI in mice, which may be attributed to the preservation of myelin and Schwann cell re-myelination. These findings may provide practical therapeutic options for patients with acute PNI.

Axon-dependent expression of YAP/TAZ mediates Schwann cell remyelination but not proliferation after nerve injury.

Previously we showed that YAP/TAZ promote not only proliferation but also differentiation of immature Schwann cells (SCs), thereby forming and maintaining the myelin sheath around peripheral axons (Grove et al., 2017). Here we show that YAP/TAZ are required for mature SCs to restore peripheral myelination, but not to proliferate, after nerve injury. We find that YAP/TAZ dramatically disappear from SCs of adult mice concurrent with axon degeneration after nerve injury. They reappear in SCs only if axons regenerate. YAP/TAZ ablation does not impair SC proliferation or transdifferentiation into growth promoting repair SCs. SCs lacking YAP/TAZ, however, fail to upregulate myelin-associated genes and completely fail to remyelinate regenerated axons. We also show that both YAP and TAZ are redundantly required for optimal remyelination. These findings suggest that axons regulate transcriptional activity of YAP/TAZ in adult SCs and that YAP/TAZ are essential for functional regeneration of peripheral nerve.

Lithium promotes proliferation and suppresses migration of Schwann cells.

Schwann cell proliferation, migration and remyelination of regenerating axons contribute to regeneration after peripheral nervous system injury. Lithium promotes remyelination by Schwann cells and improves peripheral nerve regeneration. However, whether lithium modulates other phenotypes of Schwann cells, especially their proliferation and migration remains elusive. In the current study, primary Schwann cells from rat sciatic nerve stumps were cultured and exposed to 0, 5, 10, 15, or 30 mM lithium chloride (LiCl) for 24 hours. The effects of LiCl on Schwann cell proliferation and migration were examined using the Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, Transwell and wound healing assays. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays showed that 5, 10, 15, and 30 mM LiCl significantly increased the viability and proliferation rate of Schwann cells. Transwell-based migration assays and wound healing assays showed that 10, 15, and 30 mM LiCl suppressed the migratory ability of Schwann cells. Furthermore, the effects of LiCl on the proliferation and migration phenotypes of Schwann cells were mostly dose-dependent. These data indicate that lithium treatment significantly promotes the proliferation and inhibits the migratory ability of Schwann cells. This conclusion will inform strategies to promote the repair and regeneration of peripheral nerves. All of the animal experiments in this study were ethically approved by the Administration Committee of Experimental Animal Center of Nantong University, China (approval No. 20170320-017) on March 2, 2017.

Abstract # 2077 Neuroprotective and antiinflammatory effects of propentofylline following a gliotoxic lesion in the rat brainstem

Propentofylline (PPF) is a xanthine derivative that depresses activation of glial cells, whose responses induce oxidative stress and neural tissue damage during inflammation. Ethidium bromide (EB) injection into the brain causes local oligodendroglial and astrocytic loss, resulting in primary demyelination and neuroinflammation. Surviving astrocytes present increased glial fibrillary acidic protein (GFAP) expression around the injury site. This investigation aimed to evaluate the capacity of PPF of affecting glial cell behaviour during the process of demyelination-remyelination and of altering cytokine release and lipid peroxidation (measured through its byproducts TBARS or thiobarbituric acid reactive species) in the plasma and brain. Wistar rats were injected with 0.1%EB into the cisterna pontis and treated or not with PPF (12.5 mg/kg/day, intraperitoneal) during the experimental period. Brainstem sections were collected from day (D) 7 to 31 and processed for GFAP immunohistochemistry and ultrastructural investigation. A semi-quantitative method was used to compare remyelination status. Plasma and brains were also collected for TBARS and cytokines (IL-1beta and TNF-alpha, measured by ELISA). PPF treatment decreased the levels of TBARS and cytokines in plasma and brains of EB-injected rats until D15, reduced GFAP expression until D21, and increased both oligodendroglial and Schwann cell remyelination on D31. These data suggest that PPF stimulates remyelination, decreases inflammation and redox imbalances in plasma and brain and may have a preventive role in glial scar development following gliotoxic injury.

Cellular Signal-Regulated Schwann Cell Myelination and Remyelination.

Increasing studies have demonstrated multiple signaling molecules responsible for oligodendrocytes and Schwann cells development such as migration, differentiation, myelination, and axo-glial interaction. However, complicated roles in these events are still poorly understood. This chapter focuses on well established intracellular signaling transduction and recent topics that control myelination and are elucidated from accumulating evidences. The underlying molecular mechanisms, which involved in membrane trafficking through small GTPase Arf6 and its activator cytohesins, demonstrate the crosstalk between well established intracellular signaling transduction and a new finding signaling pathway in glial cells links to physiological phenotype and essential role in peripheral nerve system (PNS). Since Arf family proteins affect the expression levels of myelin protein zero (MPZ) and Krox20, which is a transcription factor regulatory factor in early developmental stages of Schwann cells, Arf proteins likely to be key regulator for Schwann cells development. Herein, we discuss how intracellular signaling transductions in Schwann cells associate with myelination in CNS and PNS.

Macrophages Regulate Schwann Cell Maturation after Nerve Injury

Pro-regenerative macrophages are well known for their role in promoting tissue repair; however, their specific roles in promoting regeneration of the injured nerve are not well defined. Specifically, how macrophages interact with Schwann cells following injury during remyelination has been largely unexplored. We demonstrate that after injury, including in humans, macrophages function to clear debris and persist within the nerve microenvironment. Macrophage ablation immediately preceding remyelination results in an increase in immature Schwann cell density, a reduction in remyelination, and long-term deficits in conduction velocity. Targeted RNA-seq of macrophages from injured nerve identified Gas6 as one of several candidate factors involved in regulating Schwann cell dynamics. Functional studies show that the absence of Gas6 within monocyte lineage cells impairs Schwann cell remyelination within the injured nerve. These results demonstrate a role for macrophages in regulating Schwann cell function during nerve regeneration and highlight a molecular mechanism by which this occurs.

Whole Mount Immunostaining on Mouse Sciatic Nerves to Visualize Events of Peripheral Nerve Regeneration.

Injury to the peripheral nervous system triggers a series of well-defined events within both neurons and the Schwann cells to allow efficient axonal regeneration, remyelination, and functional repair. The study of these events has previously been done using sections of nerve material to analyze axonal regrowth, cell migration, and immune cell infiltration following injury. This approach, however, has the obvious disadvantage that it is not possible to follow, for instance, the path of regenerating axons in three dimensions within the nerve trunk or the nerve bridge. In order to provide a fuller picture of such events, we have developed a whole mount staining procedure to visualize blood vessel regeneration, Schwann cell migration, axonal regrowth, and remyelination in models of nerve injury.

MiR-30c promotes Schwann cell remyelination following peripheral nerve injury.

Differential expression of miRNAs occurs in injured proximal nerve stumps and includes miRNAs that are firstly down-regulated and then gradually up-regulated following nerve injury. These miRNAs might be related to a Schwann cell phenotypic switch. miR-30c, as a member of this group, was further investigated in the current study. Sprague-Dawley rats underwent sciatic nerve transection and proximal nerve stumps were collected at 1, 4, 7, 14, 21, and 28 days post injury for analysis. Following sciatic nerve injury, miR-30c was down-regulated, reaching a minimum on day 4, and was then upregulated to normal levels. Schwann cells were isolated from neonatal rat sciatic nerve stumps, then transfected with miR-30c agomir and co-cultured in vitro with dorsal root ganglia. The enhanced expression of miR-30c robustly increased the amount of myelin-associated protein in the co-cultured dorsal root ganglia and Schwann cells. We then modeled sciatic nerve crush injury in vivo in Sprague-Dawley rats and tested the effect of perineural injection of miR-30c agomir on myelin sheath regeneration. Fourteen days after surgery, sciatic nerve stumps were harvested and subjected to immunohistochemistry, western blot analysis, and transmission electron microscopy. The direct injection of miR-30c stimulated the formation of myelin sheath, thus contributing to peripheral nerve regeneration. Overall, our findings indicate that miR-30c can promote Schwann cell myelination following peripheral nerve injury. The functional study of miR-30c will benefit the discovery of new therapeutic targets and the development of new treatment strategies for peripheral nerve regeneration.

Zeb2 recruits HDAC-NuRD to inhibit Notch and controls Schwann cell differentiation and remyelination.

The mechanisms that coordinate and balance a complex network of opposing regulators to control Schwann cell (SC) differentiation remain elusive. Here we demonstrate that zinc-finger E-box binding-homeobox 2 (Zeb2/Sip1) transcription factor is a critical intrinsic timer that controls the onset of Schwann cell (SC) differentiation by recruiting HDAC1/2-NuRD co-repressor complexes. Zeb2 deletion arrests SCs at an undifferentiated state during peripheral nerve development and inhibits remyelination after injury. Zeb2 antagonizes inhibitory effectors including Notch and Sox2. Importantly, genome-wide transcriptome analysis reveals a Zeb2 target gene, encoding the Notch effector Hey2, as a potent inhibitor for SC differentiation. Strikingly, a genetic Zeb2 variant, which is associated with Mowat-Wilson syndrome, disrupts the interaction with HDAC1/2-NuRD and abolishes Zeb2 activity for SC differentiation. Therefore, Zeb2 controls SC maturation by recruiting HDAC1/2-NuRD complexes and inhibiting a novel Notch-Hey2 signaling axis, pointing to the critical role of HDAC1/2-NuRD activity in peripheral neuropathies caused by ZEB2 mutations.

Immunohistochemical and transcriptome analyses indicate complex breakdown of axonal transport mechanisms in canine distemper leukoencephalitis.

Introduction CDV‐DL (Canine distemper virus‐induced demyelinating leukoencephalitis) represents a spontaneously occurring animal model for demyelinating disorders. Axonopathy represents a key pathomechanism in this disease; however, its underlying pathogenesis has not been addressed in detail so far. This study aimed at the characterization of axonal cytoskeletal, transport, and potential regenerative changes with a parallel focus upon Schwann cell remyelination.MethodsImmunohistochemistry of canine cerebellar tissue as well as a comparative analysis of genes from an independent microarray study were performed.ResultsIncreased axonal immunoreactivity for nonphosphorylated neurofilament was followed by loss of cytoskeletal and motor proteins. Interestingly, a subset of genes encoding for neurofilament subunits and motor proteins was up‐regulated in the chronic stage compared to dogs with subacute CDV‐DL. However, immunohistochemically, hints for axonal regeneration were restricted to up‐regulated axonal positivity of hypoxia‐inducible factor 1 alpha, while growth‐associated protein 43, erythropoietin and its receptor were not or even down‐regulated. Periaxin‐positive structures, indicative of Schwann cell remyelination, were only detected within few advanced lesions.ConclusionsThe present findings demonstrate a complex sequence of axonal cytoskeletal breakdown mechanisms. Moreover, though sparse, this is the first report of Schwann cell remyelination in CDV‐DL. Facilitation of these very limited endogenous regenerative responses represents an important topic for future research.

Contribution of Schwann Cells to Remyelination in a Naturally Occurring Canine Model of CNS Neuroinflammation.

Gliogenesis under pathophysiological conditions is of particular clinical relevance since it may provide evidence for regeneration promoting cells recruitable for therapeutic purposes. There is evidence that neurotrophin receptor p75 (p75NTR)-expressing cells emerge in the lesioned CNS. However, the phenotype and identity of these cells, and signals triggering their in situ generation under normal conditions and certain pathological situations has remained enigmatic. In the present study, we used a spontaneous, idiopathic and inflammatory CNS condition in dogs with prominent lympho-histiocytic infiltration as a model to study the phenotype of Schwann cells and their relation to Schwann cell remyelination within the CNS. Furthermore, the phenotype of p75NTR-expressing cells within the injured CNS was compared to their counter-part in control sciatic nerve and after peripheral nerve injury. In addition, organotypic slice cultures were used to further elucidate the origin of p75NTR-positive cells. In cerebral and cerebellar white and grey matter lesions as well as in the brain stem, p75NTR-positive cells co-expressed the transcription factor Sox2, but not GAP-43, GFAP, Egr2/Krox20, periaxin and PDGFR-α. Interestingly, and contrary to the findings in control sciatic nerves, p75NTR-expressing cells only co-localized with Sox2 in degenerative neuropathy, thus suggesting that such cells might represent dedifferentiated Schwann cells both in the injured CNS and PNS. Moreover, effective Schwann cell remyelination represented by periaxin- and P0-positive mature myelinating Schwann cells, was strikingly associated with the presence of p75NTR/Sox2-expressing Schwann cells. Intriguingly, the emergence of dedifferentiated Schwann cells was not affected by astrocytes, and a macrophage-dominated inflammatory response provided an adequate environment for Schwann cells plasticity within the injured CNS. Furthermore, axonal damage was reduced in brain stem areas with p75NTR/Sox2-positive cells. This study provides novel insights into the involvement of Schwann cells in CNS remyelination under natural occurring CNS inflammation. Targeting p75NTR/Sox2-expressing Schwann cells to enhance their differentiation into competent remyelinating cells appears to be a promising therapeutic approach for inflammatory/demyelinating CNS diseases.

Astrocyte Activation via Stat3 Signaling Determines the Balance of Oligodendrocyte versus Schwann Cell Remyelination

Remyelination within the central nervous system (CNS) most often is the result of oligodendrocyte progenitor cells differentiating into myelin-forming oligodendrocytes. In some cases, however, Schwann cells, the peripheral nervous system myelinating glia, are found remyelinating demyelinated regions of the CNS. The reason for this peripheral type of remyelination in the CNS and what governs it is unknown. Here, we used a conditional astrocytic phosphorylated signal transducer and activator of transcription 3 knockout mouse model to investigate the effect of abrogating astrocyte activation on remyelination after lysolecithin-induced demyelination of spinal cord white matter. We show that oligodendrocyte-mediated remyelination decreases and Schwann cell remyelination increases in lesioned knockout mice in comparison with lesioned controls. Our study shows that astrocyte activation plays a crucial role in the balance between Schwann cell and oligodendrocyte remyelination in the CNS, and provides further insight into remyelination of CNS axons by Schwann cells.

Complex axonal transport disturbances and evidence of schwann cell remyelination in Cdv-induced demyelinating leucoencephalitis

Complex axonal transport disturbances and evidence of schwann cell remyelination in Cdv-induced demyelinating leucoencephalitis