Insulin-like growth factor-1 inhibits mature oligodendrocyte apoptosis during primary demyelination. (1/102)

Metabolic insult results in apoptosis and depletion of mature oligodendrocytes during demyelination. To examine the role of insulin-like growth factor-1 (IGF-1) during acute demyelination and remyelination in the adult CNS, we exposed transgenic mice that continuously express IGF-1 (IGF-1 tg) to cuprizone intoxication. Demyelination was observed within the corpus callosum in both wild-type and IGF-1 tg mice 3 weeks after exposure to cuprizone. Wild-type mice showed significant apoptotic mature oligodendrocytes and a dramatic loss of these cells within the lesion that resulted in near complete depletion and demyelination by week 5. In contrast, the demyelinated corpus callosum of the IGF-1 tg mice was near full recovery by week 5. This rapid recovery was apparently caused by survival of the mature oligodendrocyte population because apoptosis was negligible, and by week 4, the mature oligodendrocyte population was completely restored. Furthermore, despite demyelination in both wild-type and IGF-1 tg mice, oligodendrocyte progenitors accumulated only in the absence of mature oligodendrocytes and failed to accumulate if the mature oligodendrocytes remained as demonstrated in the IGF-1 tg mice. These results suggest that IGF-1 may be important in preventing the depletion of mature oligodendrocytes in vivo and thus facilitates an early recovery from demyelination.  (+info)

Absence of macrophage-inflammatory protein-1alpha delays central nervous system demyelination in the presence of an intact blood-brain barrier. (2/102)

Chemokines are small chemotactic cytokines that modulate leukocyte recruitment and activation during inflammation. Here, we describe the role of macrophage inflammatory protein-1alpha (MIP-1alpha) during cuprizone intoxication, a model where demyelination of the CNS features a large accumulation of microglia/macrophage without T cell involvement or blood-brain barrier disruption. RNase protection assays showed that mRNA for numerous chemokines were up-regulated during cuprizone treatment in wild-type, C57BL/6 mice. RANTES, inflammatory protein-10, and monocyte chemoattractant protein-1 showed greatest expression with initiation of insult at 1-2 wk of treatment, whereas MIP-1alpha and beta increased later at 4-5 wk, coincident with peak demyelination and cellular accumulation. The function of MIP-1alpha during demyelination was tested in vivo by exposing MIP-1alpha knockout mice (MIP-1alpha(-/-)) to cuprizone and comparing pathology to wild-type mice. Demyelination at 3.5 wk of treatment was significantly decreased in MIP-1alpha(-/-) mice ( approximately 36% reduction), a result confirmed by morphology at the electron microscopic level. The delay in demyelination was correlated to apparent decreases in microglia/macrophage and astrocyte accumulation and in TNF-alpha protein levels. It was possible that larger effects of the MIP-1alpha deficiency were being masked by other redundant chemokines. Indeed, RNase protection assays revealed increased expression of several chemokine transcripts in both untreated and cuprizone-treated MIP-1alpha(-/-) mice. Nonetheless, despite this possible compensation, our studies show the importance of MIP-1alpha in demyelination in the CNS and highlight its effect, particularly on cellular recruitment and cytokine regulation.  (+info)

Interleukin-1beta promotes repair of the CNS. (3/102)

Interleukin-1beta (IL-1beta) is a proinflammatory cytokine associated with the pathophysiology of demyelinating disorders such as multiple sclerosis and viral infections of the CNS. However, we demonstrate here that IL-1beta appears to promote remyelination in the adult CNS. In IL-1beta(-/-) mice, acute demyelination progressed similarly to wild-type mice and showed parallel mature oligodendrocyte depletion, microglia-macrophage accumulation, and the appearance of oligodendrocyte precursors. In contrast, IL-1beta(-/-) mice failed to remyelinate properly, and this appeared to correlate with a lack of insulin-like growth factor-1 (IGF-1) production by microglia-macrophages and astrocytes and to a profound delay of precursors to differentiate into mature oligodendrocytes. Thus, IL-1beta may be crucial to the repair of the CNS, presumably through the induction of astrocyte and microglia-macrophage-derived IGF-1.  (+info)

The protective role of nitric oxide in a neurotoxicant-induced demyelinating model. (4/102)

Demyelination is often associated with acute inflammatory events involving the recruitment-activation of microglia/macrophage, astrocytes, and leukocytes. The ultimate role of inflammatory products in demyelinating disease and in the survival of oligodendrocytes, the myelin forming cells, is unresolved. The current study examines the role of inducible NO synthase (iNOS)-derived NO in a neurotoxicant-induced model of demyelination. NO levels were greatly elevated in the midline corpus callosum during demyelination in genetically intact C57BL/6 mice, and this NO was due solely to the induction of iNOS, as the correlates of NO were not found in mice lacking iNOS. C57BL/6 mice lacking iNOS exhibited more demyelination, but did not display an increased overall cellularity in the corpus callosum, attributable to an unimpeded microglia/macrophage presence. An enhanced course of pathology was noted in mice lacking iNOS. This was associated with a greater depletion of mature oligodendrocytes, most likely due to apoptosis of oligodendrocytes. Microglia and astrocytes did not undergo apoptosis during treatment. Our results suggest a moderately protective role for NO during acute inflammation-association demyelination.  (+info)

Absence of fibroblast growth factor 2 promotes oligodendroglial repopulation of demyelinated white matter. (5/102)

This study takes advantage of fibroblast growth factor 2 (FGF2) knock-out mice to determine the contribution of FGF2 to the regeneration of oligodendrocytes in the adult CNS. The role of FGF2 during spontaneous remyelination was examined using two complementary mouse models of experimental demyelination. The murine hepatitis virus strain A59 (MHV-A59) model produces focal areas of spinal cord demyelination with inflammation. The cuprizone neurotoxicant model causes extensive corpus callosum demyelination without a lymphocytic cell response. In both models, FGF2 expression is upregulated in areas of demyelination in wild-type mice. Surprisingly, in both models, oligodendrocyte repopulation of demyelinated white matter was significantly increased in FGF2 -/- mice compared with wild-type mice and even surpassed the oligodendrocyte density of nonlesioned mice. This dramatic result indicated that the absence of FGF2 promoted oligodendrocyte regeneration, possibly by enhancing oligodendrocyte progenitor proliferation and/or differentiation. FGF2 -/- and +/+ mice had similar oligodendrocyte progenitor densities in normal adult CNS, as well as similar progenitor proliferation and accumulation during demyelination. To directly analyze progenitor differentiation, glial cultures from spinal cords of wild-type mice undergoing remyelination after MHV-A59 demyelination were treated for 3 d with either exogenous FGF2 or an FGF2 neutralizing antibody. Elevating FGF2 favored progenitor proliferation, whereas attenuating endogenous FGF2 activity promoted the differentiation of progenitors into oligodendrocytes. These in vitro results are consistent with enhanced progenitor differentiation in FGF2 -/- mice. These studies demonstrate that the FGF2 genotype regulates oligodendrocyte regeneration and that FGF2 appears to inhibit oligodendrocyte lineage differentiation during remyelination.  (+info)

Insulin-like growth factor (IGF) signaling through type 1 IGF receptor plays an important role in remyelination. (6/102)

We examined the role of IGF signaling in the remyelination process by disrupting the gene encoding the type 1 IGF receptor (IGF1R) specifically in the mouse brain by Cre-mediated recombination and then exposing these mutants and normal siblings to cuprizone. This neurotoxicant induces a demyelinating lesion in the corpus callosum that is reversible on termination of the insult. Acute demyelination and oligodendrocyte depletion were the same in mutants and controls, but the mutants did not remyelinate adequately. We observed that oligodendrocyte progenitors did not accumulate, proliferate, or survive within the mutant mice, compared with wild type, indicating that signaling through the IGF1R plays a critical role in remyelination via effects on oligodendrocyte progenitors.  (+info)

Insulin-like growth factor I gene expression is induced in astrocytes during experimental demyelination. (7/102)

To investigate insulin-like growth factor I (IGF-I) and IGF-I receptor gene expression during experimental demyelination and myelin regeneration, young mice were fed cuprizone (( bis(cyclohexanone) oxaldihydrazone )). This copper-chelating agent produces demyelination in the corpus callosum and superior cerebellar peduncles, and when treatment is stopped, there is rapid remyelination. At intervals during cuprizone treatment and recovery, brain sections were hybridized with specific probes and immunostained with antibodies to determine the localization and relative amounts of IGF-I and IGF-I receptor mRNAs and peptides. In untreated littermates, IGF-I and IGF-I receptor mRNAs and peptides were not detected in white matter. In cuprizone-treated mice, high levels of both IGF-I mRNA and peptide were expressed by astrocytes in areas of myelin breakdown. Astrocyte IGF-I expression decreased rapidly during recovery and oligodendroglial expression of myelin-related genes increased. In severely demyelinated areas, immature oligodendroglia exhibited a transient increase in IGF-I receptor mRNA and peptide immunoreactivity during early recovery. This highly specific pattern of IGF-I induction in astrocytes during demyelination and the expression of the IGF-I receptor in regenerating oligodendrocytes during recovery suggest that IGF-I functions in the regulation of oligodendrocyte and myelin metabolism in vivo.  (+info)

Functional genomic analysis of remyelination reveals importance of inflammation in oligodendrocyte regeneration. (8/102)

Tumor necrosis factor alpha (TNFalpha), a proinflammatory cytokine, was shown previously to promote remyelination and oligodendrocyte precursor proliferation in a murine model for demyelination and remyelination. We used Affymetrix microarrays in this study to identify (1) changes in gene expression that accompany demyelination versus remyelination and (2) changes in gene expression during the successful remyelination of wild-type mice versus the unsuccessful attempts in mice lacking TNFalpha. Alterations in inflammatory genes represented the most prominent changes, with major histocompatibility complex (MHC) genes dramatically enhanced in microglia and astrocytes during demyelination, remyelination, and as a consequence of TNFalpha stimulation. Studies to examine the roles of these genes in remyelination were then performed using mice lacking specific genes identified by the microarray. Analysis of MHC-II-null mice showed delayed remyelination and regeneration of oligodendrocytes, whereas removal of MHC-I had little effect. These data point to the induction of MHC-II by TNFalpha as an important regulatory event in remyelination and emphasize the active inflammatory response in regeneration after pathology in the brain.  (+info)

The cuprizone model is a well-established and investigated paradigm to study demyelination and remyelination in rodents. Cuprizone is usually administrated by mixing in the powdered or pelleted rodent chow. However, since cuprizone is sensitive to the environment and the consumption of it varies between different animals, the major issue is the discrepancy in demyelination of the animals. This study reports the development of the cuprizone model by gavage administrations in mice. Following testing a series of doses of cuprizone, 400 mg/kg/day was found to be the best dosage to induce dramatic and consistent demyelination after 5 weeks of administration; while remyelination quickly occurred after 9 days of cuprizone withdrawal ...
Previous studies have clearly demonstrated the indispensable role of IL-17 in the induction and pathogenesis of EAE, which resembles the pattern I and II MS lesions driven by T cell-mediated autoimmune inflammatory response. In this study, we show for the first time that IL-17-mediated signaling plays a critical role in cuprizone-induced demyelination, which shares similarities with pattern III MS lesions associated with apoptosis of myelin-forming oligodendrocytes and pronounced loss of oligodendrocytes. Interestingly, mice deficient in IL-17A, IL-17RC, and adaptor protein Act1 (of IL-17R) displayed diminished demyelination, microglial accumulation, and leukocyte infiltration compared with that in wild-type mice in response to cuprizone. Importantly, astrocytes are highly responsive to IL-17 in vitro, and selective deletion of Act1 in astrocytes ameliorated cuprizone-induced demyelination. Together, these results suggest that IL-17-mediated signaling in astrocytes contributes to the ...
Figure 1. BM-derived cells are recruited in a CCR2-dependent manner into demyelinating sites of the CNS in the cuprizone model. (A) A Busulfan/Cyclophosphamide chemotherapy regimen was used to prepare WT mice to receive the injection of BM cells from GFP+/− mice. 6 wk after transplantation, 0.2% Cuprizone was added to the diet for up to 6 wk. Mice were sacrificed after 2, 3, 4, 5, and 6 wk on a cuprizone-supplemented diet. Another group was sacrificed 2 wk after removing cuprizone from the diet to allow remyelination. (B) Flow cytometry analysis of GFP expression in circulating monocytes of WT mice, GFP+/− mice, chimeric GFP → WT mice, and and CCR2−/− → WT mice. (C) GFP+ cells were counted with a stereologic apparatus. Reported is the total number of GFP+ cells per slice counted per animal. (D-F) Representative confocal images of GFP+ cells (green) and immunoreactive Iba1+ cells (red) in the hippocampus and corpus callosum of chimeric mice either untreated (D) or after 5 wk of ...
Neurotrophin signaling impacts development and health of oligodendrocyte lineage cells. Brain-derived neurotrophic factor (BDNF) has been of particular interest. BDNF increases DNA synthesis in cultured basal forebrain oligodendrocyte progenitors (Vant Veer et al., 2009) and enhances oligodendrocyte differentiation to myelin protein-expressing cells (Du et al., 2006). Moreover, BDNF deficient mice exhibit deficits in progenitors and myelin protein expression (Vondran et al., 2010) and the conditional knock-out of the BDNF receptor TrkB from mature, MBP+ oligodendrocytes results in reduced myelin thickness in both the spinal cord and the corpus callosum (Wong et al., 2013).. These effects may be relevant to in vivo demyelination. For example, in the cuprizone demyelination model expression of BDNF is decreased in the corpus callosum, and animals deficient in BDNF exhibit a more severe loss of myelin protein in the lesioned corpus callosum than do their wild-type littermates (VonDran et al., ...
Baxi, E.G., DeBruin, J., Jin, J., Strasburger, H.J., Smith, M.D., Orthmann-Murphy, J.L., Schott, J.T., Fairchild, A.N., Bergles, D.E., and Calabresi, P.A. (2017). Lineage tracing reveals dynamic changes in oligodendrocyte precursor cells following cuprizone-induced demyelination. Glia 65, 2087-2098.. Kim, J., Hughes, E.G., Shetty, A.S., Arlotta, P., Goff, L.A., Bergles, D.E., and Brown, S.P. (2017). Changes in the Excitability of Neocortical Neurons in a Mouse Model of Amyotrophic Lateral Sclerosis Are Not Specific to Corticospinal Neurons and Are Modulated by Advancing Disease. J. Neurosci. 37, 9037-9053.. Assinck, P., Duncan, G.J., Plemel, J.R., Lee, M.J., Stratton, J.A., Manesh, S.B., Liu, J., Ramer, L.M., Kang, S.H., Bergles, D.E., et al. (2017). Myelinogenic Plasticity of Oligodendrocyte Precursor Cells following Spinal Cord Contusion Injury. J. Neurosci. 37, 8635-8654.. Langseth, A.J., Kim, J., Ugolino, J.E., Shah, Y., Hwang, H.-Y., Wang, J., Bergles, D.E., and Brown, S.P. (2017). ...
The present study aimed to orally deliver methylthioadenosine (MTA) to the brain employing solid lipid nanoparticles (SLNs) for the management of neurological conditions like multiple sclerosis. The stearic acid-based SLNs were below 100 nm with almost neutral zeta potential and offered higher drug entrapment and drug loading. Cuprizone-induced demyelination model in mice was employed to mimic the multiple sclerosis-like conditions. It was observed that the MTA-loaded SLNs were able to maintain the normal metabolism, locomotor activity, motor coordination, balancing, and grip strength of the rodents in substantially superior ways vis-à-vis plain MTA. Histopathological studies of the corpus callosum and its subsequent staining with myelin staining dye luxol fast blue proved the potential of MTA-loaded SLNs in the remyelination of neurons. The pharmacokinetic studies provided the evidences for improved bioavailability and enhanced bioresidence supporting the pharmacodynamic findings. The studies ...
Charles River conducts studies in both inflammation-induced and demyelination in vivo MS models (cuprizone model and EAE model) to test the efficacy of novel therapeutics.
Histone deacetylase 1 (HDAC1) is a nuclear enzyme involved in transcriptional repression. We detected cytosolic HDAC1 in damaged axons in brains of humans with multiple sclerosis and of mice with cuprizone-induced demyelination, in ex vivo models of demyelination and in cultured neurons exposed to g …
A study shows that the natural metabolite taurine appears to boost remyelination and the effectiveness of current multiple sclerosis (MS) therapies.
Walsh DA, Merson TD, Landman KA, Hughes BD. (2016) Evidence for Cooperative Selection of Axons for Myelination by Adjacent Oligodendrocytes in the Optic Nerve. PLoS ONE 11 (11): e0165673. Walsh DA, Röth PT, Holmes WR, Landman KA, Merson TD, Hughes BD. (2016) Is cell migration or proliferation dominant in the formation of linear arrays of oligodendrocytes? J Theor Biol 406:17-30.. Huang L, Merson TD, Bourne JA. (2016) In vivo whole brain, cellular and molecular imaging in nonhuman primate models of neuropathology. Neurosci Biobehav Rev 66:104-118.. Mitew S, Xing YL, Merson TD. (2016) Axonal activity-dependent myelination in development: insights for myelin repair. J Chem Neuroanat pii: S0891-0618(16)30029-1. Xing YL, Röth PT, Stratton JA, Chuang BHA, Danne J, Ellis SL, Ng SW, Kilpatrick TJ, Merson TD. (2014) Adult neural precursor cells from the subventricular zone contribute significantly to oligodendrocyte regeneration and remyelination. J Neurosci 34:14128-46.. Merson TD, Bourne JA. (2014) ...
Walsh DA, Merson TD, Landman KA, Hughes BD. (2016) Evidence for Cooperative Selection of Axons for Myelination by Adjacent Oligodendrocytes in the Optic Nerve. PLoS ONE 11 (11): e0165673. Walsh DA, Röth PT, Holmes WR, Landman KA, Merson TD, Hughes BD. (2016) Is cell migration or proliferation dominant in the formation of linear arrays of oligodendrocytes? J Theor Biol 406:17-30.. Huang L, Merson TD, Bourne JA. (2016) In vivo whole brain, cellular and molecular imaging in nonhuman primate models of neuropathology. Neurosci Biobehav Rev 66:104-118.. Mitew S, Xing YL, Merson TD. (2016) Axonal activity-dependent myelination in development: insights for myelin repair. J Chem Neuroanat pii: S0891-0618(16)30029-1. Xing YL, Röth PT, Stratton JA, Chuang BHA, Danne J, Ellis SL, Ng SW, Kilpatrick TJ, Merson TD. (2014) Adult neural precursor cells from the subventricular zone contribute significantly to oligodendrocyte regeneration and remyelination. J Neurosci 34:14128-46.. Merson TD, Bourne JA. (2014) ...
Radiotherapy is the mainstay of treatment after surgery for high-grade gliomas and is usually well tolerated. Radiation toxicity in the brain is usually classified according to the timing of side effects in relation to treatment, as either acute (during radiotherapy), early delayed (within 12 weeks of radiotherapy) or late delayed (months to years after radiotherapy). We report two cases of young women who developed severe acute demyelination within 4 months of radiotherapy for glioma, one of whom had a previous history of transverse myelitis. Both improved with corticosteroids and remain in tumour remission. These cases emphasise the importance of careful discussion with patients before starting radiotherapy if there is a previous history of central nervous system demyelination or multiple white matter lesions on MRI. ...
High resolution diffusion tensor images of the mouse brain were acquired using the pulsed gradient spin echo sequence and the oscillating gradient spin echo sequence. The oscillating gradient spin echo tensor images demonstrated frequency-dependent changes in diffusion measurements, including apparent diffusion coefficient and fractional anisotropy, in major brain structures. Maps of the rate of change in apparent diffusion coefficient with oscillating gradient frequency revealed novel tissue contrast in the mouse hippocampus, cerebellum, and cerebral cortex. The observed frequency-dependent contrasts resembled neuronal soma-specific Nissl staining and nuclei-specific 4,6-diamidino-2-phenylindole (DAPI) staining in the mouse brain, which suggests that the contrasts might be related to key features of cytoarchitecture in the brain. In the mouse cuprizone model, oscillating gradient spin echo-based diffusion MRI revealed significantly higher frequency-dependence of perpendicular diffusivity (λ() ...
Demyelinating diseases, such as multiple sclerosis and leukodystrophy, are characterized by damage to the protective myelin sheath that surrounds the axons of neurons. This demyelination can be caused by an autoimmune response or impaired myelin production by oligodendrocytes.. A new report in JCI Insight from Arjun Saha and colleagues at Duke University demonstrates that a cell therapy product called DUOC-01 can accelerate remyelination of axons in mice treated with a demyelinating chemical agent. DUOC-01 cells, which are derived from banked umbilical cord blood, were transplanted into mice following toxic demyelination. DUOC-01 treatment resulted in faster remyelination and promoted the differentiation of oligodendrocyte progenitor cells. These results suggest that a cord blood-derived cell product can promote neuronal repair and remyelination. Future clinical studies will be needed to determine if DUOC-01 cell therapy benefits patients with demyelinating diseases.. ...
Both diets decreased disease severity compared to the control group but the Ketogenic Diet had more modest effects and did not reverse EAE progression in mice. The FMD mice group had clinical reductions to disease symptoms including higher blood levels of corticosterone, improvements in cytokines and T- Cells and a.. May 26, 2016. Moreover, the FMD promoted oligodendrocyte precursor cell regeneration and remyelination in axons in both EAE and cuprizone MS models, supporting its effects on both suppression of autoimmunity and remyelination. We also report preliminary data suggesting that an FMD or a chronic ketogenic diet.. A ketogenic diet. this is the diet for you. Instead, the idea is to rotate when and what you eat in three different phases to put your metabolism into overdrive. The FMD focuses on eating real food and cutting out fad diet nonsense like.. 5 day water fast results tracked via blood ketones, blood glucose and weight. Step by step walk through and experiences of several ...
Individual Test Kits (Copper) A yellow color is formed when copper reacts with diethyldithiocarbamate (DDC). A blue color is formed when copper reacts with cuprizone. ...
B,C) Analysis indicates the total distance was unchanged between cuprizone-exposed mice with or without clemastine treatment (B), but the distance in the central field decreased upon 6-week exposure to cuprizone, while clemastine gradually rescued the behavioral change (C). *P ...
There is much evidence to support the goal of remyelination as a means to prevent axon degeneration and slow deficit progression in neurologic disease [14]. In the year 2000, we reported the identification of a natural human IgM that promoted robust spinal cord remyelination in both the TMEV-IDD and lysolecithin-induced demyelination models [15, 16]. A recombinant form of this human IgM, termed rHIgM22, was expressed in a F3B6 cell line with the assembled IgM containing a mouse J chain [17]. rHIgM22 binds to myelin and the surface of oligodendrocytes (OL) and in pre-clinical studies is effective in vivo at very low doses. A single 0.025 mg/kg intraperitoneal injection of rHIgM22 given to TMEV-IDD mice with demyelination promoted significant remyelination 5 weeks later [18] and increased brainstem NAA concentrations [13], indicating a preservation of axon health [19]. In a recently concluded dose escalation clinical trial in humans with MS, rHIgM22 was tested at doses ranging from 0.025 up to 2 ...
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A healthy diet including fish, eggs, vegetables, poultry, and legumes may lower the risk for central nervous system demyelination.
Valery, Patricia C., Lucas, Robyn M., Williams, David B., Pender, Michael P., Chapman, Caron, Coulthard, Alan, Dear, Keith, Dwyer, Terence, Kilpatrick, Trevor. J., McMichael, Anthony J., van, der Mei, Ingrid, Taylor, Bruce and Ponsonby, Anne-Louise (2013). Occupational Exposure and Risk of Central Nervous System Demyelination. American Journal of Epidemiology,177(9):954-961. ...
Neuroprotective approaches for central nervous system regeneration have not been successful in clinical practice so far and compounds that enhance remyelination are still not available for patients with multiple sclerosis. The objective of this study was to determine potential regenerative effects of the substance cytidine-5-diphospho (CDP)-choline in two different mouse animal models of multiple sclerosis. The effects of exogenously applied CDP-choline were tested in mouse myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. In addition, the cuprizone-induced mouse model of de- and remyelination was used to specifically test the hypothesis that CDP-choline directly increases remyelination. We found that CDP-choline ameliorated the disease course of experimental autoimmune encephalomyelitis and exerted beneficial effects on myelin, oligodendrocytes and axons. After cuprizone-induced demyelination, CDP-choline effectively enhanced myelin regeneration and ...
The pathogenesis of murine hepatitis virus, strain JHM, was studied in 6- and 12-week-old C57iBL mice. There was 100% mortality in the 6-week-old mice after intracerebral inoculation. The lesions were characterized by necrotizing encephalomyelitis, without demyelination. Intracerebral inoculation of 12-week-old animals, however, resulted in no morbidity or mortality. The 12-week-old animals showed transient virus replication in the brain, spinal cord, and liver, which was cleared by day 14. Histologic examination showed evidence of ongoing demyelination, concomitant remyelination, and hydrocephalus ex vacuo. Although viral antigen was demonstrated by immunofluorescence in the central nervous system of these animals, no infectious virus was recovered, and immunosuppression regimens did not potentiate the disease.. ...
Hoare S, Lithander F, van der Mei I, Ponsonby AL, Lucas R. Higher intake of omega-3 polyunsaturated fatty acids is associated with a decreased risk of a first clinical diagnosis of central nervous system demyelination: Results from the Ausimmune Study. Multiple sclerosis (Houndmills, Basingstoke, England) (2015) PubMed ...
Center for Immunology and Immune Therapies at Mayo Clinic: Clinical trials on ALS, cancer, central nervous system demyelination, immune function and more.
This study provides compelling evidence that in marmoset EAE, which forms lesions strongly resembling those of MS, early changes in vascular permeability are associated with perivascular inflammatory cuffing and parenchymal microglial activation but precede the arrival of blood-derived monocytes tha …
Learn more about a study that found giving estrogen to two different adult mouse models of multiple sclerosis promoted remyelination.
Read about Endece receiving a n additional U.S. patent covering NDC-1308 therapy, seen in early studies to have potential to induce remyelination in MS.
Although our knowledge about the formation of oligodendrocytes and their progenitors has grown enormously during the past two decades, the formulation of specif...
Multiple Sclerosis (MS) is an inflammatory disease which causes areas of demyelination in the Central Nervous System (CNS) and affects only humans. Current therapies for MS are focused on anti-inflammatory treatment, which reduce the occurrence and clinical relapses of the disease. However, progressive disability of the disease is related to axonal degeneration. After demyelination, remyelination occurs, which helps repair the demyelinated lesions and protects axons from degeneration. However, this endogenous remyelination is inefficient, and currently there are no therapies available to enhance remyelination. The aim of this thesis was to first characterize a fast and reliable model to study CNS remyelination in vitro, and second to investigate the role of semaphorin 3a (Sema3A) and semaphorin 3f (Sema3F) signaling in CNS remyelination. Various in vivo models have been developed to investigate the pathology of multiple sclerosis, and can be used to test remyelination therapies. However, in vivo ...
However, French Secretary of State for Health Dr Bernard Kouchner took the decision to ban the jab in light of evidence that the vaccine could cause multiple sclerosis or other forms of central nervous system demyelination. Studies in both France and Britain have shown that, in school aged children, the risk of demyelinating reactions in the central nervous system increases during the two months after vaccination (BMJ, 1998; 317: 1034 ...
SUPERVISORS: OLE DIDRIK LÆRUM, ØYSTEIN BRUSERUD 2000 DR.MED. PEER KÅRE LILLENG. TUMOUR CELLS IN THE AXILLARY NODES IN PATIENTS WITH BREAST CANCER. SUPERVISORS: FLORA HARTVEIT, BJØRN MÆHLE.. 1999 DR.MED. HANS KRISTIAN HAUGLAND. MODULATION OF INVASIVE BEHAVIOR IN CULTURED HUMAN GLIOMA CELLS. SUPERVISOR: OLE DIDRIK LÆRUM. 1998 DR.MED. LARS BØ. MULTIPLE SCLEROSIS. IMMUNOPATHOLOGICAL STUDIES OF INFLAMMATORY CENTRAL NERVOUS SYSTEM DEMYELINATION. SUPERVISOR: SVERRE MØRK. 1999 DR.MED. LARS FJELLBIRKELAND. THREE-DIMENSIONAL CULTURE OF HUMAN BRONCHIAL MUCOSA AND LUNG CANCER TISSUE. SUPERVISORS: OLE DIDRIK LÆRUM, ROLF BJERKVIG. 1998 DR.MED. JOHANNA OLWEUS. EARLY EVENTS IN HUMAN MYELOPOIESIS. SUPERVISORS: OLE DIDRIK LÆRUM, FRIDTJOF LUND-JOHANSEN. 1998 DR.MED. SVEIN JACOB TJOFLAAT NYGAARD. DYNAMIC DETERMINATION AND MODULATION OF GLIOMA CELL INVASION IN VITRO. SUPERVISORS: OLE DIDRIK LÆRUM, OLE BJØRN TYSNES. 1998 DR.MED. KARIN COLLETT. OPERABLE BREAST CANCER. SUPERVISORS: BJØRN MÆHLE, ROLV ...
Three sequential symplicity studies investigated the neural and retinal diseases ng et potenciju lek za levitra al. The posterior lip of linea alba serratus anterior m. Tibia tibialis anterior m. We pre- fer lap instead of limitations. We should try to look at the central nervous system demyelination and axonal regrowth of injured spinal cord: Engraftment of neural progenitor cell transplantation it is recommended b-lymphocytes, sympathetic and all the before mentioned measures. 6. Dreger nm, degener s, ahmad-nejad p, wobker g, roth s. Urosepsis-etiology, diagnosis, and judged to be key to clinical situations (acute cardiovascular or minimised by and in undiagnosed vaginal bleeding, thromboembolic dis- of too much ergotamine can lead to a tertiary bronchus (b) left upper quadrant (hypochondriac region) the second or third week, follow the same finding (in the costal margin on the trigone. On the other drug, enhancing its ow out of the avourings thiopentone- and methohexitone-induced anaesthesia ...
Central nervous system (CNS) myelination is important for proper nervous system function in vertebrates. In demyelinating diseases such as multiple sclerosis, autoimmune-mediated myelin destruction results in neurological impairment; and although remyelination does occur spontaneously, it is poorly understood and insufficient in humans. Zebrafish (Danio rerio) are known to harbour tremendous regenerative capacity of various CNS tissues; however, there is presently only little knowledge of their myelin repair efficiency. An experimental model of myelin injury in zebrafish would permit study of the mechanisms involved in successful remyelination and could potentially guide the development of novel therapeutic agents for mammalian remyelination. This doctoral thesis describes the characterisation of the novel myelin protein Claudin k in zebrafish, demonstrates the establishment of adult zebrafish as an experimental model for CNS de- and remyelination and explores some mechanisms underlying myelin ...
Magnetization transfer imaging represents an attempt to develop contrast in MR imaging on the basis of submolecular exchange processes that may occur in biological tissue (21). This technique has some clinical and research applications in the study of different CNS disorders (22), because it affords a potential window into the macromolecular environment that is not directly visible using conventional techniques (21). Therefore, it enables the assessment of invisible disease in the so-called normal-appearing white matter (23-25), and, with the application of MTR, it provides a means to quantify disease burden (26).. Experimental and human studies support the hypothesis that demyelination and axonal loss are the main contributors to the MTR decrease observed in association with several pathologic conditions, such as experimental autoimmune encephalomyelitis (12), toxic demyelination (27), progressive multifocal leukoencephalopathy (28), human immunodeficiency virus encephalitis (28), and ...
Dr Jessica Fletcher, funded by an MS Research Australia Postdoctoral Fellowship, with the support of the Trish MS Research Foundation, has been working with Dr Simon Murray and Dr Junhua Xiao at The University of Melbourne, investigating novel molecular targets for promoting remyelination in the brain. Myelin coats the nerve cells in the brain and spinal cord. In MS there is damage to the myelin, and in the early stages of the disease there is some ability to repair the myelin, a process known as remyelination. Over time the bodys ability to remyelinate becomes impaired, leading to incomplete repair and contributing to the progression of MS symptoms. It is crucial to identify potential new treatment targets that can promote myelin repair, prevent nerve damage and halt MS disease progression.. Dr Fletcher has been working on a nerve growth factor, known as brain-derived neurotrophic factor (BDNF), which has been found to promote myelination by activating different receptors, or docking stations, ...
Remyelination can be extensive in multiple sclerosis despite a long disease course 21 April 2007 Patani R, Balaratnam M, Vora A, Reynolds R. Department of Cellular and Molecular Neuroscience, UK MS Tissue Bank, Division of Neuroscience, Imperial College London, Charing ...
Research on myelination offers centered on identifying molecules capable of inducing oligodendrocyte (OL) differentiation in an effort to develop strategies that promote functional myelin regeneration in demyelinating disorders. of and gene manifestation, mediated from the connection of SMAD3/4 with Sp1 and FoxO1 transcription factors. Our study is the 1st to demonstrate an autonomous and important part of TGF signaling in OL development and CNS myelination, and may provide new avenues in the treatment of demyelinating diseases. studies have shown that O-2A progenitor cells express TGF1 and that TGF signaling activation exerts an anti-mitogenic effect countering PDGFR signaling, in turn promoting cell cycle arrest (McKinnon et al., 1993). Moreover, Activin-A, a member of the TGF superfamily, has been proposed as one of the cytokines secreted by microglial cells that plays a role in OL regeneration and remyelination (Miron et al., 2013). These scholarly research claim that TGF signaling could be ...
TY - PAT. T1 - Treatment of Demyelinating Disorders with Soluble Lymphotoxin-Beta-Receptor. AU - Browning,Jeffrey L.. AU - Ting,Jenny P-Y. N1 - Status: published applicationnumber: 12/446,041 usclass: 514/19.2 ; 514/1.1; 530/351 applicationnumber: 12/446,041. PY - 1800. Y1 - 1800. N2 - Methods of treating a demyelinating disorder using inhibitors of the lymphotoxin pathway.. AB - Methods of treating a demyelinating disorder using inhibitors of the lymphotoxin pathway.. M3 - Patent. M1 - 8067375. ER - ...
Remyelination is the process of propagating oligodendrocyte precursor cells to form oligodendrocytes to create new myelin sheaths on demyelinated axons in the CNS. This is a process naturally regulated in the body and tends to be very efficient in a healthy CNS. The process creates a thinner myelin sheath than normal, but it helps to protect the axon from further damage, from overall degeneration, and proves to increase conductance once again. Demyelinating diseases, such as Multiple Sclerosis, have been of utmost interest within the last couple of decades. Recent research is uncovering some of the many unknown pathways involved with remyelination in hopes of battling demyelinating diseases like MS which can ultimately cripple a person. While no treatment exists yet in preventing remyelination failure in the chronic stages of these diseases, future research may yet prove to unlock key pathways that can be targeted. Remyelination is activated and regulated by a variety of factors surrounding ...
We set up the Cambridge Centre for Myelin Repair in 2005, with the aim of developing treatments that promote myelin repair for people with MS.. Since it opened the Cambridge Centre has created a world-class research environment involving researchers from all around the UK - most notably at our Edinburgh Centre for MS Research.. Scientists at both centres have worked together to show that a molecule called RXR-gamma could encourage the brains own stem cells to repair myelin in animal models of MS. Researchers will now test the benefits of a drug that targets RXR-gamma, called bexarotene, in a phase 2 clinical trial.. We announced four more years of funding for the Cambridge Centre in 2016. Researchers will continue to investigate the fundamental mechanisms behind myelin repair, with the hope of developing new treatments.. They will focus on understanding more about the cells capable of repairing myelin, and the impact ageing and lifestyle factors (such as diet and exercise) can have on these ...
Top 10 tissues for 1171_s_at (Homo sapiens, Affymetrix Probeset): cerebral cortex astrocyte, peripheral blood anergic B-cell, fetal oligodendrocyte progenitor cell, cerebral white matter oligodendrocyte progenitor cell, cerebral cortex oligodendrocyte progenitor cell, telencephalon oligodendrocyte progenitor cell, oligodendrocyte progenitor cell, tumor derived oligodendrocyte progenitor cell, sural nerve, blood neutrophil granulocyte
In the present study, we show that hypomyelination in the MLIV mouse brain is associated with decreased expression of both precursor and mature oligodendrocyte markers, as well as a decrease in the number of postmitotic oligodendrocytes. Our observation of delayed myelin deposition during early postnatal brain development highlights the developmental character of brain pathology in MLIV. Interestingly, our data also indicate that the fate of developing oligodendrocytes is affected differently in the white (corpus callosum) versus gray (neocortex) matter of the brain as indicated by changes in CC+ cell counts (Fig. 4) or PLP and MBP staining intensities in these brain regions. This suggests that the tissue microenvironment and factors released by neighboring cells can contribute to the ability of Mcoln1−/− oligodendrocytes to develop, survive and/or produce myelin. Despite these region-specific changes within the brain, our data demonstrate that TRPML1 is an important regulator of ...
Demyelinating Disorders of the Central Nervous System in Childhood von Chabas/Waubant Chabas/Waubant und Buchbewertungen gibt es auf ReadRate.com. Bücher können hier direkt online erworben werden.
Dr. Fabrizio Salvi- Head neurologist at the University of Bologna spoke of his clinical observations as a neurologist working with the CCSVI paradigm for three years. He told us that in 500 MS patients he has tested now, 100% have CCSVI. He stated the doppler is a wonderful tool of diagnosis and their needs to be training in the technique. He has a hypothesis as to why there are different varieties of screening in high risk subjects- because prognosis is related to the type of malformation. He wants to answer the question if the Liberation procedure is a disease modifying treatment in MS. He will give proof tomorrow that there is plasticity and remyelination in the CNS and the Liberation procedure have proven to activate remyelination in the CNS as shown by MRI ...
Video articles in JoVE about myelin basic proteins include Monitoring Cleaved Caspase-3 Activity and Apoptosis of Immortalized Oligodendroglial Cells using Live-cell Imaging and Cleaveable Fluorogenic-dye Substrates Following Potassium-induced Membrane Depolarization.
Graham S.T. Smith is the author of this article in the Journal of Visualized Experiments: Monitoring Cleaved Caspase-3 Activity and Apoptosis of Immortalized Oligodendroglial Cells using Live-cell Imaging and Cleaveable Fluorogenic-dye Substrates Following Potassium-induced Membrane Depolarization
Eighteen patients with acquired demyelinating syndromes and multiple sclerosis were included, the total annual incidence being 1.15/100,000 (acquired demyelinating syndromes 1.02 and multiple sclerosis 0.45/100,000). The median age at diagnosis was 14.25 years (range 1.25-17.5 years). Thirteen patients were initially diagnosed with clinically isolated syndrome, two had acute disseminated encephalomyelitis, two had multiple sclerosis, and one had neuromyelitis optica. Seven children were diagnosed with multiple sclerosis; three patients with clinically isolated syndrome developed multiple sclerosis after the age of 18 and were not included in the multiple sclerosis group. The gender ratio was equal. Of the nine girls, seven were diagnosed with clinically isolated syndrome. Most patients (11 of 18) were diagnosed during the period January through March. Oligoclonal bands in cerebrospinal fluid were exclusively found in patients with multiple sclerosis and clinically isolated syndrome and 13 of 14 ...
Current treatment modalities for the neurodegenerative disease multiple sclerosis (MS) use disease-modifying immunosuppressive compounds but do not promote repair. Although several potential targets that may induce myelin production have been identified, there has yet to be an approved therapy that promotes remyelination in the damaged central nervous system (CNS). Remyelination of damaged axons requires the generation of new oligodendrocytes from oligodendrocyte progenitor cells (OPCs). Although OPCs are detected in MS lesions, repair of myelin is limited, contributing to progressive clinical deterioration. In the CNS, the chemokine CXCL12 promotes remyelination via CXCR4 activation on OPCs, resulting in their differentiation into myelinating oligodendrocytes. Although the CXCL12 scavenging receptor CXCR7/ACKR3 (CXCR7) is also expressed by OPCs, its role in myelin repair in the adult CNS is unknown. ...
Previously we reported that a 5-hour exposure of 6-day-old (P6) rhesus macaques to isoflurane triggers robust neuron and oligodendrocyte apoptosis. In an attempt to further describe the window of vulnerability to anesthetic neurotoxicity, we exposed P20 and P40 rhesus macaques to 5 h of isoflurane anesthesia or no exposure (control animals). Brains were collected 3 h later and examined immunohistochemically to analyze neuronal and glial apoptosis. Brains exposed to isoflurane displayed neuron and oligodendrocyte apoptosis distributed throughout cortex and white matter, respectively. When combining the two age groups (P20 + P40), the animals exposed to isoflurane had 3.6 times as many apoptotic cells as the control animals. In the isoflurane group, approximately 66% of the apoptotic cells were oligodendrocytes and 34% were neurons. In comparison, in our previous studies on P6 rhesus macaques, approximately 52% of the dying cells were glia and 48% were neurons. In conclusion, the present data ...
Demyelinating Disorders is a chapter in the book, Neurology, containing the following 2 pages: Multiple Sclerosis, Guillain Barre Syndrome.
MS Focus: the Multiple Sclerosis Foundation provides grants and services to meet the critical needs of people with MS and their families.
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Myelin is the insulation sheath around nerve fibres. If this protective layer is injured, the affected nerves are no longer functional. The adult brain contains …
Silverstroff, L.; Batucci, S.; Pasquini, J.; Franco, P. (2012). "Cuprizone-induced demyelination in the rat cerebral cortex and ... "The cyclooxygenase-2 pathway via the pge₂ ep2 receptor contributes to oligodendrocytes apoptosis in cuprizone-induced ...
... the resolution of status spongiosus and remyelination in cuprizone intoxication in mice". J. Neurocytol. 1 (4): 413-26. doi: ...
"Cerebroside synthesis as a measure of the rate of remyelination following cuprizone-induced demyelination in brain". Journal of ...
... lacking mice also exhibit a different regulation of this protein after oligodendrocyte damage induced by the chemical cuprizone ...
Toxic exposures to methionine sulfoxime, cuprizone, isoniazid, triethyl tin, hexachlorophene, and hydrogen cyanide have been ...
Transfer of Myelin-Reactive Th17 Cells Impairs Endogenous Remyelination in the Central Nervous System of Cuprizone-Fed Mice ... Astrocyte-Derived BDNF Supports Myelin Protein Synthesis after Cuprizone-Induced Demyelination Clifton G. Fulmer, Melissa W. ...
... the cuprizone model reflects a toxic experimental model. Cuprizone-induced demyelination in animals is accepted for studying MS ... The cuprizone animal model: new insights into an old story Acta Neuropathol. 2009 Dec;118(6):723-36. doi: 10.1007/s00401-009- ... The present article reviews recent data concerning the cuprizone model and its relevance for MS. Particular focus is given to ... We also aim to distinguish acute and chronic demyelination under cuprizone including processes such as spontaneous ...
After cuprizone, the HA+ non-GFAP+ cells are greatly reduced. When cuprizone-treated mice are injected with ACPD, there is an ... Cuprizone treatment. Demyelination was initiated by feeding 8-week-old wild-type male mice or HA male mice 0.2% cuprizone ( ... To evaluate the effects of ACPD in the cuprizone model, wild-type mice treated with cuprizone received a single stereotaxic ... Wild-type mice were fed control or cuprizone-laden food for 4 weeks. NF-L+ axons fail to colocalize with (a) mGluR1, or (b) ...
Using transgenic mice to fate map and to selectively kill SVZ-derived eNPCs in the cuprizone demyelination model, we observed ... First, we fate mapped SVZ-eNPCs in cuprizone-induced demyelination and found that SVZ endogenous neural stem/precursor cells ... When we ablated SVZ-derived eNPCs during cuprizone-induced demyelination in female mice, the animals displayed reduced numbers ... Neural Stem Cells of the Subventricular Zone Contribute to Neuroprotection of the Corpus Callosum after Cuprizone-Induced ...
... the effects of cuprizone on the functions of the peripheral nervous system, as well as differential effects it may exert on ... Cuprizone induces massive demyelination in the CNS; however, ... Cuprizone led to a reduction in the NCV, CMAP amplitude and ... Cuprizone induces massive demyelination in the CNS; however, the effects of cuprizone on the functions of the peripheral ... S. Love, "Cuprizone neurotoxicity in the rat: Morphologic observations," J. Neurol. Sci., 84, Nos. 2/3, 223-237 (1988).CrossRef ...
C57Bl/6 mice were fed chow containing 0.7% cuprizone for 1 week, followed by 3 weeks of a 0.2% cuprizone diet. Linagliptin (10 ... Linagliptin attenuated cuprizone-induced oxidative stress by decreasing brain thiobarbituric acid reactive substances along ... Home » Topics » Spinal Cord Disorders » Research » Neuroprotective effect of linagliptin against cuprizone-induced ... This study investigated the possible neuroprotective effect of linagliptin against cuprizone-induced demyelination in mice and ...
We aimed to investigate the effect of multiple i.p. BM-MSCs injections in the cuprizone model of multiple sclerosis in mice. ... Methods: Adult male C57BL/6 mice (n = 40) were fed a regular diet or a diet containing cuprizone (0.2% w/w) for 6 six weeks. ... We aimed to investigate the effect of multiple i.p. BM-MSCs injections in the cuprizone model of multiple sclerosis in mice. ... Cuprizone could decrease myelin-binding protein mRNAs expression in corpus callosum, which was significantly recovered after BM ...
A common model of acute demyelination oral administration of copper-depleting cuprizone (CPZ) holds promise for defining ... Chronic white matter atrophy after acute cuprizone exposure may be due to transmissible misfolded proteins ...
To analyze its role in the demyelinating situation, we employed cuprizone (CPZ)-induced demyelination model in mice, which is ... To analyze its role in the demyelinating situation, we employed cuprizone (CPZ)-induced demyelination model in mice, which is ... Cuprizone Administration. To induce demyelination in 10-week-old ICR male mice, they were administered a diet containing 0.4% ... Cuprizone (CPZ)-induced experimental demyelination is a suitable rodent model to study the mechanisms leading to demyelination ...
... can increase cell vitality after being treated with cuprizone. Additional studies examined the solubility of cuprizone and ... In this proposal, we further examine the chemical and toxicological properties of cuprizone. Immunofluorescence imaging and ... Taken altogether, this experiment reveals that cuprizone affects lysosomal and mitochondrial function, and provides insight ... Cuprizone is a copper chelator that induces demyelination in the central nervous system when fed to mice. This compound is ...
Cuprizone Autoimmune Encephalitis (CAE) Model. In addition to diphtheria-toxin, cuprizone is a demyelinating neurotoxin that ... Long-term of cuprizone feeding in mice lead to oligodendrocyte death, demyelination and gliosis (Matsushima and Morell, 2001; ... 2015). Thymic atrophy and apoptosis of CD4+CD8+ thymocytes in the cuprizone model of multiple sclerosis. PLoS One 10:e0129217. ... Sen, M. K., Mahns, D. A., Coorssen, J. R., and Shortland, P. J. (2019b). Behavioural phenotypes in the cuprizone model of ...
Animals were fed with 0.2% w/w cuprizone added to ground breeder chow ad libitum for six weeks. At day 0 after cuprizone ... Index: IMEMR (Eastern Mediterranean) Main subject: Adipose Tissue / Cuprizone / Mesenchymal Stem Cell Transplantation / Mice ... Promotion of remyelination by adipose mesenchymal stem cell transplantation in a cuprizone model of multiple sclerosis ... Promotion of remyelination by adipose mesenchymal stem cell transplantation in a cuprizone ...
Four groups of rats were treated with normal saline, cuprizone, M. oleifera and a combination of M. oleifera and cuprizone, for ... Cuprizone is a neurotoxin with copper-chelating ability used in animal model of multiple sclerosis in which oxidative stress ... Animals , Brain , Catalase , Cuprizone , Hippocampus , Memory , Memory, Short-Term , Models, Animal , Moringa oleifera , ... Cuprizone significantly induced oxidative and nitrosative stress coupled with memory decline and cortico-hippocampal neuronal ...
... as compared to cuprizone-treated mice with control MSC grafts and/or cuprizone-treated mice without MSC injection. In the first ... Next, CNS inflammation and demyelination was induced by means of a cuprizone-supplemented diet. The influence of IL13-MSC ... limits cuprizone-induced microgliosis, oligodendrocyte death and demyelination. Furthermore, we here demonstrate that injection ... and to interfere with oligodendrocyte death and demyelinating events in the cuprizone mouse model. ...
... without cuprizone)" and at "3 and 5 weeks cuprizone feeding" in the new Figure 8. Unfortunately, we could not expand the data ... Alleviation of cuprizone-induced demyelination in SIRPα cKO mice.. (A) Control (SIRPα-flox:- (Ctrl)) or SIRPα cKO (SIRPα-flox: ... Cuprizone model of demyelination. Request a detailed protocol Control (SIRPα-flox:-) or SIRPα cKO (SIRPα-flox:Cx3cr1CreERT2) ... Alleviation of cuprizone-induced demyelination in the brain white matter of microglia-specific SIRPα-deficient mice. Although ...
Silverstroff, L.; Batucci, S.; Pasquini, J.; Franco, P. (2012). "Cuprizone-induced demyelination in the rat cerebral cortex and ... "The cyclooxygenase-2 pathway via the pge₂ ep2 receptor contributes to oligodendrocytes apoptosis in cuprizone-induced ...
... cuprizone, 111 ± 3%; n = 6-8, *p , 0.01. E, Time course and raw traces comparing the effects of cuprizone, tricine, and l-cys ... Bovine serum albumin (BSA), DTT, l-cys, l-histidine (L-his), tricine, and Zn2+ were dissolved in H2O; cuprizone, 5,5′dithio-bis ... whereas the relatively Cu2+-selective chelator cuprizone effected a smaller, but significant, current increase (Fig. 4D,E). ...
... the resolution of status spongiosus and remyelination in cuprizone intoxication in mice". J. Neurocytol. 1 (4): 413-26. doi: ...
Demyelination by cuprizone diet. Mice were placed on a diet of 0.2% (wt/wt) cuprizone mixed into chow pellets. Mice were ... MH helped with tamoxifen injection and cuprizone feeding. HF, MY, and HM provided autopsied samples. M Konishi and NI ... Peripheral macrophage recruitment in cuprizone-induced CNS demyelination despite an intact blood-brain barrier. J Neuroimmunol ... Kondo A, Nakano T, Suzuki K. Blood-brain barrier permeability to horseradish peroxidase in twitcher and cuprizone-intoxicated ...
Cuprizone induced demyelination. Chow containing 0.2% cuprizone (Harlan Teklad) was fed to C57Bl mice (N = 7) ad libitum for 3 ... Cuprizone demyelination does not cause CD45 activation in the SVZ. A, B) CD45 expression is minimal in control corpus callosum ... Cuprizone induced demyelination does not induce CD45 activation in the SVZ. We next asked whether the massive CD45 cell ... Cuprizone, a copper chelating agent induces demyelination in a variety of CNS regions including immediately above the SVZ, in ...
The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system. ... Home » Papers » The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system ...
The 129/Sv mice received cuprizone with food daily for 3 weeks. From day 8 of cuprizone diet, the rhLIF was injected daily (50 ... In cuprizone-treated mice of both age groups (especially in young), the number of brain T-cells increased. RhLIF injections ... The effect of both cuprizone and rhLIF on thymic endocrine function and the number of brain macrophages and T-lymphocytes in ... Hormone level decreased after 3-week cuprizone treatment only in young mice. After 7 days, the number of brain macrophages in ...
PET imaging of demyelination and remyelination in the cuprizone mouse model for multiple sclerosis: a comparison between [11C] ... Transplantation into adult shiverer mice resulted in phenotypic rescue; it also ameliorated demyelination in a cuprizone mouse ... 2. Focus on benztropine; PLP-induced EAE model; T cell independent cuprizone model*. 11:03 ... with demyelination chemically induced using cuprizone) suggested that benzatropine works by enhancing myelination. However, ...
Torkildsen, Øivind Fredvik; Brunborg, Linn Anne Bjelland; Myhr, Kjell-Morten; Bø, Lars. 2008. The cuprizone model for ... Wergeland, Stig; Torkildsen, Øivind; Myhr, Kjell-Morten; Mørk, Sverre; Bø, Lars. 2012. The cuprizone model: regional ... A salmon based diet protects mice from behavioural changes in the cuprizone model for demyelination. Clinical Nutrition. 83-87 ... Fish diet prevents impaired mobility in the murine cuprizone model for multiple sclerosis. Multiple Sclerosis. S90-S91. ...
Dietary Vitamin D3 Supplements Reduce Demyelination in the Cuprizone Model  Wergeland, Stig; Torkildsen, Øivind; Myhr, Kjell- ...
In addition, cuprizone-induced demyelination was alleviated by the microglia-specific ablation of SIRPα. Thus, microglial SIRPα ... cuprizone (Cpz) diet. After 3 or 5 wks of Cpz feeding (Cpz 3 wks, Cpz 5 wks), brain samples were prepared. Other groups of mice ...
Evidence from a cuprizone-induced model of demyelination, in vitro and in vivo T-cell assays and EAE adoptive transfer ...
Christakoudi, S., Tsilidis, K. K., Muller, D. C., Freisling, H., Weiderpass, E., Overvad, K., Söderberg, S., Häggström, C., Pischon, T., Dahm, C. C., Zhang, J., Tjønneland, A., Halkjær, J., MacDonald, C., Boutron-Ruault, M-C., Mancini, F. R., Kühn, T., Kaaks, R., Schulze, M. B., Trichopoulou, A. & 27 others, Karakatsani, A., Peppa, E., Masala, G., Pala, V., Panico, S., Tumino, R., Sacerdote, C., Quirós, J. R., Agudo, A., Sánchez, M-J., Cirera, L., Barricarte-Gurrea, A., Amiano, P., Memarian, E., Sonestedt, E., Bueno-de-Mesquita, B., May, A. M., Khaw, K-T., Wareham, N. J., Tong, T. Y. N., Huybrechts, I., Noh, H., Aglago, E. K., Ellingjord-Dale, M., Ward, H. A., Aune, D. & Riboli, E., 3 Sep 2020, In : Scientific Reports. 10, 1, 15 p., 14541.. Research output: Contribution to journal › Journal article › Research › peer-review ...
Roenhoej Rønhøj, R., Hasselbalch, R. B., Schultz, M., Pries-Heje, M., Plesner, L. L., Ravn, L., Lind, M., Jensen, B. N., Hoei-Hansen Høi-Hansen, T., Carlson, N., Torp-Pedersen, C., Rasmussen, L. S., Rasmussen, L. J. H., Eugen-Olsen, J., Koeber Køber, L. & Iversen, K., mar. 2020, I : Clinical Biochemistry. 77, s. 14-19 6 s.. Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review ...
  • Following cuprizone-elicited demyelination in mice, astrocytes contain BDNF and increase levels of metabotropic receptors. (jneurosci.org)
  • When we ablated SVZ-derived eNPCs during cuprizone-induced demyelination in female mice, the animals displayed reduced numbers of oligodendrocytes within the lesioned CC. Although this reduction in oligodendrocytes did not impact the ensuing remyelination, eNPC-ablated mice experienced increased axonal loss. (nih.gov)
  • Using transgenic mice to fate map and to selectively kill SVZ-derived eNPCs in the cuprizone demyelination model, we observed migration of SVZ-eNPCs after injury and their contribution to oligodendrogenesis and axonal survival. (nih.gov)
  • Neuroprotective effect of linagliptin against cuprizone-induced demyelination and behavioural dysfunction in mice: A pivotal role of AMPK/SIRT1 and JAK2/STAT3/NF-κB signalling pathway modulation. (bioportfolio.com)
  • This study investigated the possible neuroprotective effect of linagliptin against cuprizone-induced demyelination in mice and its potential early-remyelinating properties. (bioportfolio.com)
  • C57Bl/6 mice were fed chow containing 0.7% cuprizone for 1 week, followed by 3 weeks of a 0.2% cuprizone diet. (bioportfolio.com)
  • In conclusion, linagliptin exerted a neuroprotective effect in mice with cuprizone-induced demyelination possibly by modulating AMPK/SIRT1 and JAK2/STAT3/NF-κB signalling pathways. (bioportfolio.com)
  • BM-MSCs injections in the cuprizone model of multiple sclerosis in mice. (ac.ir)
  • Adult male C57BL/6 mice (n = 40) were fed a regular diet or a diet containing cuprizone (0.2% w/w) for 6 six weeks. (ac.ir)
  • BM-MSCs in the cuprizone model of multiple sclerosis in mice. (ac.ir)
  • To analyze its role in the demyelinating situation, we employed cuprizone (CPZ)-induced demyelination model in mice, which is characterized by oligodendrocyte-specific apoptosis, followed by the strong glial activation, demyelination, and repopulation of OLs. (frontiersin.org)
  • Cuprizone is a copper chelator that induces demyelination in the central nervous system when fed to mice. (uakron.edu)
  • At day 0 after cuprizone removal, mice were randomly divided into two groups the ADSCs-transplanted group and the control vehicle group [received medium alone]. (bvsalud.org)
  • The influence of IL13-MSC grafting on neuropathological alterations was monitored by non-invasive T 2 -weighted magnetic resonance imaging (MRI) and quantitative histological analyses, as compared to cuprizone-treated mice with control MSC grafts and/or cuprizone-treated mice without MSC injection. (biomedcentral.com)
  • The mice were treated by Cuprizone for five weeks in order to induce demyelination. (magiran.com)
  • It is concluded that vitamin D3 increases MBP expression in the corpus callosum of cuprizone-induced demyelination mice. (magiran.com)
  • In the lab, Tiwari-Woodruff and her team induced demyelination in mice by feeding them a diet that contained cuprizone, a copper-binding substance that causes damage to oligodendrocytes -the brain cells that produce myelin. (eurekalert.org)
  • After nine weeks of feeding them cuprizone, the majority of mice started having seizures. (eurekalert.org)
  • In another study, after nine or twelve weeks, the researchers stopped feeding the mice the cuprizone diet. (eurekalert.org)
  • In one UCR study, the six-person team fed mice cuprizone, a copper-binding substance that damages brain cells that produce myelin, for nine weeks and found the mice later had seizures. (pe.com)
  • In a second study, researchers stopped feeding the mice cuprizone after nine or 12 weeks. (pe.com)
  • The tissue study, which was recently funded by the National MS Society, will investigate how much cuprizone-fed mice research reproduces changes in humans. (pe.com)
  • dfMRI differentiated functional deficits in CC of cuprizone mice. (wustl.edu)
  • After 5-week cuprizone feeding, mice developed severe demyelination at CC. (wustl.edu)
  • 3) Functional assessment with DBSI: Currently, Abby applies DBSI/dfMRI to study optic nerve and corpus callosum of EAE, cuprizone, traumatic brain injury (TBI), and Huntington's disease mice to understand interplay of function deficits and pathology in CNS. (wustl.edu)
  • In adult mice, Sema6A expression is upregulated in demyelinating lesions in cuprizone-treated mice. (wingsforlife.com)
  • J Am Vet Med Assoc 169:228-229, 1976 Evidence for a "Dying-Back" Gliopathy in Demyelinating Disease samuel K. ~ ~ dMB, ~ ~ ic h~ , , and Edward S. Johnson, MD# Recurrent demyelination was produced in mice by Cuprizone administration. (docme.ru)
  • D-F) Representative confocal images of GFP + cells (green) and immunoreactive Iba1 + cells (red) in the hippocampus and corpus callosum of chimeric mice either untreated (D) or after 5 wk of treatment with a cuprizone diet in GFP (E) and CCR2 −/− (F) chimeric mice. (rupress.org)
  • As a result, Trem2 -/- mice exhibited impaired myelin debris clearance, axonal dystrophy, oligodendrocyte reduction, and persistent demyelination after prolonged cuprizone treatment. (jci.org)
  • However, cuprizone-fed mice subjected to 0.5 mg/Kg of WIN-55,212-2 displayed no differences when compared to controls during demyelination, although there was a robust increase in the myelinated axons during the remyelination phase. (thisisms.com)
  • The present study evaluated the protective effect of melatonin on demyelination and remyelination processes in male and female mice with experimental MS induced by cuprizone. (medworm.com)
  • This model of experimental MS in mice is widely used because cuprizone administration causes an artificial demyelination reaction through oligodendrocyte apoptosis, while its withdrawal leads to spontaneous remyelination. (medworm.com)
  • Male and female SWR/J mice (n = 78) were divided into three main groups (control, cuprizone, and cuprizone + melatonin), which were each further subdivided into males and females. (medworm.com)
  • Trem2 -/- mice also differ from wild-type mice in their responses to experimental demyelination induced by oral administration of the copper chelator cuprizone (CPZ). (alzforum.org)
  • Cuprizone-induced demyelination in animals is accepted for studying MS-related lesions and is characterized by degeneration of oligodendrocytes rather than by a direct attack on the myelin sheet. (nih.gov)
  • Psychological stress effects on myelin degradation in the cuprizone-induced model of demyelination. (bioportfolio.com)
  • Cuprizone could decrease myelin-binding protein mRNAs expression in corpus callosum, which was significantly recovered after BM-MSCs injections. (ac.ir)
  • In the cuprizone model of oligodendrocyte degeneration and demyelination, Trem2 -/- microglia failed to amplify transcripts indicative of activation, phagocytosis, and lipid catabolism in response to myelin damage. (jci.org)
  • The present study aims to assess the effects of the cannabinoid agonist WIN-55,212-2 in cuprizone fed animals on myelin repair capacity. (thisisms.com)
  • Animals exposed to cuprizone were simultaneously treated withWIN-55,212-2, behaviorally tested and finally the corpus callosum was exhaustively studied by Western blotting, qRT-PCR and a myelin staining procedure. (thisisms.com)
  • Linagliptin attenuated cuprizone-induced oxidative stress by decreasing brain thiobarbituric acid reactive substances along with restoring reduced glutathione levels. (bioportfolio.com)
  • Cuprizone is a neurotoxin with copper-chelating ability used in animal model of multiple sclerosis in which oxidative stress has been documented as one of the cascade in the pathogenesis. (bvsalud.org)
  • Resveratrol effectively enhanced motor coordination and balance, reversed cuprizone-induced demyelination , improved mitochondrial function, alleviated oxidative stress, and inhibited NF-κB signaling. (thisisms.com)
  • Demyelination and remyelination in anatomically distinct regions of the corpus callosum following cuprizone intoxication. (tamu.edu)
  • In the second part of this study, we demonstrate that grafting of IL13-MSC, in addition to the recruitment of M2 polarised macrophages, limits cuprizone-induced microgliosis, oligodendrocyte death and demyelination. (biomedcentral.com)
  • Controlled and localised production of IL13 by means of intracerebral MSC grafting has the potential to modulate cell graft- and pathology-associated microglial/macrophage responses, and to interfere with oligodendrocyte death and demyelinating events in the cuprizone mouse model. (biomedcentral.com)
  • Loss of Nampt reduces neural stem/progenitor cell‐derived oligodendrocyte regeneration after cuprizone‐induced demyelination. (embopress.org)
  • Neural Stem Cells of the Subventricular Zone Contribute to Neuroprotection of the Corpus Callosum after Cuprizone-Induced Demyelination. (nih.gov)
  • First, we fate mapped SVZ-eNPCs in cuprizone-induced demyelination and found that SVZ endogenous neural stem/precursor cells are recruited during the remyelination phase to the corpus callosum (CC) and are capable of forming new oligodendrocytes. (nih.gov)
  • Histologically, cuprizone induced demyelination in the corpus callosum. (ac.ir)
  • In this study، the effects of Vitamin D3 on total protein concentration (TPC) and MBP expression in the corpus callosum extracts of Cuprizone induced demyelinated mouse has been investigated. (magiran.com)
  • Taken altogether, this experiment reveals that cuprizone affects lysosomal and mitochondrial function, and provides insight into leucine supplementation at an attempt to rescue cells from neurotoxicity. (uakron.edu)
  • While experimental allergic encephalomyelitis is one of the most frequently used models to investigate MS pathology and therapeutic interventions, the cuprizone model reflects a toxic experimental model. (nih.gov)
  • The combined use of chronic and relapsing remitting experimental autoimmune encephalomyelitis (C-EAE, R-EAE) ("outside-in") as well as progressive diphtheria toxin A chain ( DTA) and cuprizone autoimmune encephalitis (CAE) ("inside-out") mouse models allow for the investigation and specific targeting of all three of these MS-associated disease parameters. (frontiersin.org)
  • The EAE (experimental autoimmune encephalomyelitis) series of MS models are widely used to test therapies targeting the inflammation component of MS, while MS models where demyelination is induced by cuprizone, lysolecithin, or ethidium bromide are increasingly being used to test therapeutic candidates. (criver.com)
  • Finally, we point at strain and gender differences in this animal model and highlight the contribution of some growth factors and cytokines during and after cuprizone intoxication, including LIF, IGF-1, and PDGFalpha. (nih.gov)
  • Immunofluorescence imaging and microarray data on MO3.13 cells treated with cuprizone revealed the possibility of alterations in lysosomal function, as well as mitochondrial disruption via mTOR and Electron Transport Chain (ETC) related pathways. (uakron.edu)
  • This study aimed at evaluating the ameliorative capability of M. oleifera in cuprizone-induced behavioral and histopathological alterations in the prefrontal cortex and hippocampus of Wistar rats. (bvsalud.org)
  • Lack of cuprizone-induced demyelination in the murine spinal cord despite oligodendroglial alterations substantiates the concept of site-specific susceptibilities of the central nervous system. (tiho-hannover.de)
  • Her team was recently awarded a pilot grant from the National Multiple Sclerosis Society to compare postmortem brain tissue from MS patients with seizures to those without to understand the cellular basis of seizures in MS. Their findings will also be used to check how well the cuprizone mouse model reproduces the changes seen in humans. (eurekalert.org)
  • The present article reviews recent data concerning the cuprizone model and its relevance for MS. Particular focus is given to the concordance and difference between human MS patterns (types I-IV lesions) and cuprizone-induced histopathology, including a detailed description of the sensitive brain regions extending the observations to different white and grey matter structures. (nih.gov)
  • Similarities between pattern III lesions and cuprizone-induced demyelination and dissimilarities, such as inflamed blood vessels or the presence of CD3+ T cells, are outlined. (nih.gov)
  • In addition, cuprizone-induced demyelination was alleviated by the microglia-specific ablation of SIRPα. (elifesciences.org)
  • however, administration of M. oleifera significantly reversed the neuropathological deficits induced by cuprizone. (bvsalud.org)
  • Arecoline attenuates memory impairment and demyelination in a cuprizone-induced mouse model of schizophrenia. (bioportfolio.com)
  • 6 wk after transplantation, 0.2% Cuprizone was added to the diet for up to 6 wk. (rupress.org)
  • We also aim to distinguish acute and chronic demyelination under cuprizone including processes such as spontaneous remyelination during acute demyelination. (nih.gov)
  • A common model of acute demyelination oral administration of copper-depleting cuprizone (CPZ) holds promise for defining mechanisms of progressive degeneration. (ectrims-congress.eu)
  • Histological analysis revealed clear demyelination after being fed cuprizone for three weeks. (thisisms.com)
  • Animals were fed with 0.2% w/w cuprizone added to ground breeder chow ad libitum for six weeks. (bvsalud.org)
  • Charles River offers cuprizone- and lysolecithin-induced rodent models of demyelination to test novel therapies for MS. The cuprizone model uses a validated study design where demyelination is induced followed by a recovery period of remyelination. (criver.com)
  • Notably, electrophysiological observations reveal that cuprizone affects both female and male rats, but males are more sensitive. (springer.com)
  • BM-MSCs (2 × 10 6 in 1 milliliter medium) were administered intraperitoneally for two consecutive weeks at the end of the forth weeks of cuprizone administration. (ac.ir)
  • Four groups of rats were treated with normal saline, cuprizone, M. oleifera and a combination of M. oleifera and cuprizone, for five weeks. (bvsalud.org)
  • Cuprizone was orally administered at a dose of 400 mg/kg/day by oral gavage for 5 weeks. (medworm.com)
  • Toll-Like Receptor 2-Mediated Glial Cell Activation in a Mouse Model of Cuprizone-Induced Demyelination. (uni-muenchen.de)
  • Sulfasalazine alters microglia phenotype by competing endogenous RNA effect of miR-136-5p and long non-coding RNA HOTAIR in cuprizone-induced demyelination. (bioportfolio.com)
  • Microglia polarization by methylprednizolone acetate accelerates cuprizone induced demyelination. (bioportfolio.com)
  • Thus, we aimed to examine changes in the electromyographic characteristics of female and male Sprague-Dawley rats with cuprizone-induced demyelination. (springer.com)
  • however, the effects of cuprizone on the functions of the peripheral nervous system, as well as differential effects it may exert on males and females, have not yet been studied. (springer.com)
  • Next, CNS inflammation and demyelination was induced by means of a cuprizone-supplemented diet. (biomedcentral.com)
  • Another group was sacrificed 2 wk after removing cuprizone from the diet to allow remyelination. (rupress.org)
  • During the second course of Cuprizone, the animals showed greater resistance to the toxin and demyelination occurred slowly and was complete only after prolonged periods. (docme.ru)
  • 1991. A comparison of spongiosis induced in the brain by hexachlorophene, cuprizone and triethyl tin in the Sprague-Dawley rat. (nih.gov)
  • Evidence from a cuprizone-induced model of demyelination, in vitro and in vivo T-cell assays and EAE adoptive transfer experiments indicated that the observed efficacy of this drug results directly from an enhancement of remyelination rather than immune suppression. (nih.gov)
  • Linagliptin treatment improved behavioural and motor abnormalities induced by cuprizone, as demonstrated by open field, rotarod and grip strength tests. (bioportfolio.com)
  • This is the first study showing gender differences for the peripheral neurotoxicity of cuprizone. (springer.com)
  • The Anti-Aging Protein Klotho Enhances Remyelination Following Cuprizone-Induced Demyelination. (bu.edu)
  • BM-derived cells are recruited in a CCR2-dependent manner into demyelinating sites of the CNS in the cuprizone model. (rupress.org)