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experimental autoimmune encephalomyelitis

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https://www.readbyqxmd.com/read/28647454/elevated-serum-met-5-enkephalin-levels-correlate-with-improved-clinical-and-behavioral-outcomes-in-experimental-autoimmune-encephalomyelitis
#1
Michael D Ludwig, Ian S Zagon, Patricia J McLaughlin
Methionine enkephalin ([Met(5)]-enkephalin, Opioid growth factor (OGF)) is a small neuropeptide with growth-related as well as immunomodulatory properties. OGF is distributed widely throughout the body, is both autocrine and paracrine produced, and has a very short half-life in serum. In addition to its neurotransmitter functions, OGF inhibits cell replication of a wide variety of cells involved in the autoimmune process. In this preclinical study, mice were immunized with myelin oligodendrocytic glycoprotein (MOG35-55) to establish a chronic progressive form of autoimmune encephalomyelitis (EAE), and serum enkephalin levels were assessed throughout the disease as well as in response to OGF therapy in order to determine whether OGF may be a biological marker for EAE and multiple sclerosis...
June 21, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28646890/influence-of-type-i-ifn-signaling-on-anti-mog-antibody-mediated-demyelination
#2
Carsten Tue Berg, Reza Khorooshi, Nasrin Asgari, Trevor Owens
BACKGROUND: Antibodies with specificity for myelin oligodendrocyte glycoprotein (MOG) are implicated in multiple sclerosis and related diseases. The pathogenic importance of anti-MOG antibody in primary demyelinating pathology remains poorly characterized. OBJECTIVE: The objective of this study is to investigate whether administration of anti-MOG antibody would be sufficient for demyelination and to determine if type I interferon (IFN) signaling plays a similar role in anti-MOG antibody-mediated pathology, as has been shown for neuromyelitis optica-like pathology...
June 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28646573/interferon-%C3%AE-regulates-dendritic-cell-activation-and-migration-in-experimental-autoimmune-encephalomyelitis
#3
Leesa M Pennell, Eleanor N Fish
CD11c+ dendritic cells (DCs) exert a critical role as antigen-presenting cells in regulating pathogenic T cells in multiple sclerosis (MS). To determine whether the therapeutic benefit of interferon (IFN)-β treatment for MS is in part influenced by IFN regulation of DC function, we examined the immunophenotype of DCs derived from IFN-β(+/+) and IFN-β(-/-) mice using a myelin oligodendrocyte glycoprotein (MOG) peptide-induced mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Our earlier work identified that IFN-β(-/-) mice exhibit earlier onset and more rapid progression of neurologic impairment compared with IFN-β(+/+) mice...
June 24, 2017: Immunology
https://www.readbyqxmd.com/read/28646336/nogo-a-antibodies-enhance-axonal-repair-and-remyelination-in-neuro-inflammatory-and-demyelinating-pathology
#4
Benjamin V Ineichen, Sandra Kapitza, Christiane Bleul, Nicolas Good, Patricia S Plattner, Maryam S Seyedsadr, Julia Kaiser, Marc P Schneider, Björn Zörner, Roland Martin, Michael Linnebank, Martin E Schwab
Two hallmarks of chronic multiple sclerosis lesions are the absence of significant spontaneous remyelination and primary as well as secondary neurodegeneration. Both characteristics may be influenced by the presence of inhibitory factors preventing myelin and neuronal repair. We investigated the potential of antibodies against Nogo-A, a well-known inhibitory protein for neuronal growth and plasticity, to enhance neuronal regeneration and remyelination in two animal models of multiple sclerosis. We induced a targeted experimental autoimmune encephalomyelitis (EAE) lesion in the dorsal funiculus of the cervical spinal cord of adult rats resulting in a large drop of skilled forelimb motor functions...
June 23, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28642092/chemokine-ccl17-is-expressed-by-dendritic-cells-in-the-cns-during-experimental-autoimmune-encephalomyelitis-and-promotes-pathogenesis-of-disease
#5
Christina Ruland, Hannes Renken, Ivan Kuzmanov, Arezoo Fattahi Mehr, Kathrin Schwarte, Manuela Cerina, Alexander Herrmann, David-Marian Otte, Andreas Zimmer, Nicholas Schwab, Sven G Meuth, Volker Arolt, Luisa Klotz, Irmgard Förster, Stefanie Scheu, Judith Alferink
The CC chemokine ligand 17 (CCL17) and its cognate CC chemokine receptor 4 (CCR4) are known to control leukocyte migration, maintenance of TH17 cells, and regulatory T cell (Treg) expansion in vivo. In this study we characterized the expression and functional role of CCL17 in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Using a CCL17/EGFP reporter mouse model, we could show that CCL17 expression in the CNS can be found in a subset of classical dendritic cells (DCs) that immigrate into the CNS during the effector phase of MOG-induced EAE...
June 19, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28642030/cyclic-mog35-55-ameliorates-clinical-and-neuropathological-features-of-experimental-autoimmune-encephalomyelitis
#6
Athanasios Lourbopoulos, George Deraos, Minos-Timotheos Matsoukas, Olga Touloumi, Aggeliki Giannakopoulou, Hubert Kalbacher, Nikolaos Grigoriadis, Vasso Apostolopoulos, John Matsoukas
EAE is induced to susceptible mice using linear peptides of myelin proteins of the central nervous system. Specific peptide motifs within the peptide-binding groove of the MHC peptide-complex determines the affinity of the peptide in each animal and the consequent T-cell receptor recognition and activation of the cell. Altered peptide ligand (APL) vaccination is a novel approach based on an effort to induce T-cell tolerance or alter cytokine profile from pro-inflammatory to anti-inflammatory. In the present study we synthesized the MOG35-55 peptide and altered its 3-dimensional conformation to make it a cyclic one (c-MOG35-55)...
June 7, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28641926/targeting-the-gm-csf-receptor-for-the-treatment-of-cns-autoimmunity
#7
Igal Ifergan, Todd S Davidson, Hania Kebir, Dan Xu, Daphne Palacios-Macapagal, Jennifer Cann, Jane M Rodgers, Zoe N Hunter, Camille L Pittet, Sara Beddow, Clare A Jones, Alexandre Prat, Matthew A Sleeman, Stephen D Miller
In multiple sclerosis (MS), there is a growing interest in inhibiting the pro-inflammatory effects of granulocyte-macrophage colony-stimulating factor (GM-CSF). We sought to evaluate the therapeutic potential and underlying mechanisms of GM-CSF receptor alpha (Rα) blockade in animal models of MS. We show that GM-CSF signaling inhibition at peak of chronic experimental autoimmune encephalomyelitis (EAE) results in amelioration of disease progression. Similarly, GM-CSF Rα blockade in relapsing-remitting (RR)-EAE model prevented disease relapses and inhibited T cell responses specific for both the inducing and spread myelin peptides, while reducing activation of mDCs and inflammatory monocytes...
June 19, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28634006/testosterone-differentially-affects-t-cells-and-neurons-in-murine-and-human-models-of-neuroinflammation-and-neurodegeneration
#8
Megan G Massa, Christina David, Stefanie Jörg, Johannes Berg, Barbara Gisevius, Sarah Hirschberg, Ralf A Linker, Ralf Gold, Aiden Haghikia
The high female-to-male sex ratio of multiple sclerosis (MS) prevalence has continuously confounded researchers, especially in light of male patients' accelerated disease course at later stages of MS. Although multiple studies have concentrated on estrogenic mechanisms of disease modulation, fairly little attention has been paid to androgenic effects in a female system, and even fewer studies have attempted to dissociate hormonal effects on the neurodegenerative and neuroinflammatory processes of MS. Herein, we demonstrate the differential effects of hormone treatment on the acute inflammatory and chronic neurodegenerative phases of murine experimental autoimmune encephalomyelitis...
July 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28629631/probenecid-treatment-reduces-demyelination-induced-by-cuprizone-feeding
#9
Nadine Hainz, Philipp Becker, Daniel Rapp, Stefan Wagenpfeil, Bodo Wonnenberg, Christoph Beisswenger, Thomas Tschernig, Carola Meier
Recent experiments showed that a pannexin-1 inhibitor, probenecid, reduced clinical symptoms in the murine experimental autoimmune encephalomyelitis when applied during the initial phase of neuronal inflammation. An inflammatory component is also present in a toxically induced inflammation and demyelination using cuprizone diet. Probenecid is a pannexin-1 antagonist and a probenecid therapy was investigated. Mice were fed for 10days with a cuprizone diet. In the following, the diet was continued but combined with a daily injection of a low dose of probenecid or solvent for 10days...
June 16, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28625726/pulmonary-administration-of-soluble-antigen-arrays-is-superior-to-antigen-in-treatment-of-experimental-autoimmune-encephalomyelitis
#10
Christopher Kuehl, Sharadvi Thati, Bradley Sullivan, Joshua Sestak, Michael Thompson, Teruna Siahaan, Cory Berkland
Antigen-specific immunotherapy (ASIT) has been used to hyposensitize patients to allergens and offers an enticing approach for attenuating autoimmune diseases. Applying ASIT to mucosal surfaces such as the lungs may engage unique immune response pathways to improve efficacy. Pulmonary delivery of soluble antigen arrays (SAgAs) was explored in mice with experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model. SAgAs were designed to impede immune response to autoantigen epitopes and are composed of a hyaluronan backbone with peptides PLP139-151 and LABL, a disease-causing proteolipid peptide epitope and an ICAM-1 ligand, respectively...
June 15, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28621170/therapeutic-efficacy-of-multipotent-adult-progenitor-cells-versus-mesenchymal-stem-cells-in-experimental-autoimmune-encephalomyelitis
#11
Saurabh Pratap Singh, Sachin Hanumantrao Jadhav, Chandra Prakash Chaturvedi, Soniya Nityanand
AIM: In this study, we have evaluated the therapeutic efficacy of mouse multipotent adult progenitor cells (mMAPCs) in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, and compared it with mouse mesenchymal stem cells (mMSCs). MATERIALS & METHODS: We administered PKH26-labeled mMAPC and mMSC into EAE mice and evaluated their therapeutic efficacy. RESULTS: The mMAPC-treated mice in comparison with the mMSC group exhibited a higher suppression of EAE (p < 0...
June 16, 2017: Regenerative Medicine
https://www.readbyqxmd.com/read/28619643/superior-transfection-efficiency-of-phagocytic-astrocytes-by-large-chitosan-dna-nanoparticles
#12
Fanqiang Kong, Guoping Liu, Shumin Zhou, Jie Guo, Song Chen, Zhiyun Wang
PURPOSE: Mechanism study of why astrocytes isolated from experimental autoimmune encephalomyelitis (EAE)-induced B6 mice or after being exposed to inflammatory factors had the highest transfection efficiency to larger-sized, but not compacted, pspCS/pDNA particles. METHODS: Phosphorylatable short peptide conjugated chitosan (pspCS) was compounded with plasmid DNA (pDNA) at different N:P ratios to form pspCS/pDNA particles of different size and zeta potentials. These pspCS/pDNA particles were used for the transfection of astrocytes isolated from either EAE induced or healthy B6 mice...
June 12, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28619431/depletion-of-cd20-b-cells-fails-to-inhibit-relapsing-mouse-experimental-autoimmune-encephalomyelitis
#13
Eseberuo Sefia, Gareth Pryce, Ute-Christiane Meier, Gavin Giovannoni, David Baker
BACKGROUND: Multiple sclerosis (MS) is often considered to be a CD4, T cell-mediated disease. This is largely based on the capacity of CD4 T cells to induce relapsing experimental autoimmune encephalomyelitis (EAE) in rodents. However, CD4-depletion using a monoclonal antibody was considered unsuccessful and relapsing MS responds well to B cell depletion via CD20 B cell depleting antibodies. The influence of CD20 B cell depletion in relapsing EAE was assessed. METHODS: Relapsing EAE was induced in Biozzi ABH mice...
May 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28618115/iron-sulfur-glutaredoxin-2-protects-oligodendrocytes-against-damage-induced-by-nitric-oxide-release-from-activated-microglia
#14
Klaudia Lepka, Katrin Volbracht, Eckhard Bill, Reiner Schneider, Natalia Rios, Thomas Hildebrandt, Jens Ingwersen, Timur Prozorovski, Christopher Horst Lillig, Jack van Horssen, Lawrence Steinman, Hans-Peter Hartung, Rafael Radi, Arne Holmgren, Orhan Aktas, Carsten Berndt
Demyelinated brain lesions, a hallmark of autoimmune neuroinflammatory diseases like multiple sclerosis, result from oligodendroglial cell damage. Activated microglia are considered a major source of nitric oxide and subsequent peroxynitrite-mediated damage of myelin. Here, we provide biochemical and biophysical evidence that the oxidoreductase glutaredoxin 2 inhibits peroxynitrite formation by transforming nitric oxide into dinitrosyl-diglutathionyl-iron-complexes. Glutaredoxin 2 levels influence both survival rates of primary oligodendrocyte progenitor cells and preservation of myelin structure in cerebellar organotypic slice cultures challenged with activated microglia or nitric oxide donors...
June 15, 2017: Glia
https://www.readbyqxmd.com/read/28617989/1-25-dihydroxyvitamin-d3-induced-dendritic-cells-suppress-experimental-autoimmune-encephalomyelitis-by-increasing-proportions-of-the-regulatory-lymphocytes-and-reducing-th1-th17-cells
#15
Zhongxiang Xie, Jingtao Chen, Chao Zheng, Jing Wu, Yun Cheng, Shan Zhu, Chenhong Lin, Qingqing Cao, Jie Zhu, Tao Jin
Dendritic cells (DCs), a bridge of innate and adaptive immune responses, play a key role in the development of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Administration of tolerogenic DCs has been used as an immunotherapy in the autoimmune diseases. Deficiency of vitamin D is an environmental risk factor of MS. In this study, we induced tolerogenic DCs by 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ) and adoptive transferred the tolerogenic DCs (VD3-DCs) into EAE mice...
June 15, 2017: Immunology
https://www.readbyqxmd.com/read/28617951/altered-expression-of-igf-i-system-in-neurons-of-the-inflamed-spinal-cord-during-acute-experimental-autoimmune-encephalomyelitis
#16
Azita Parvaneh Tafreshi, Farideh Talebi, Samira Ghorbani, Claude Bernard, Farshid Noorbakhsh
BACKGROUND: There is growing evidence that the impaired IGF-I system contributes to neurodegeneration. OBJECTIVES: In this study, we examined the spinal cords of the EAE, the animal model of multiple sclerosis, to see if the expression of the IGF-I system is altered. METHODS: To induce EAE, C57/BL6 mice were immunized with the Hooke lab MOG kit, sacrificed at the peak of the disease and their spinal cords were examined for the immunoreactivities (ir) of the IGF-I, IGF binding protein-1 (IGFBP-1) and glycogen synthase kinase 3β (GSK3β), as one major downstream molecule in the IGF-I signaling...
June 15, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28616446/treatment-with-anti-fc%C3%AE%C2%B5ri%C3%AE-antibody-exacerbates-eae-and-t-cell-immunity-against-myelin
#17
Silvia Musio, Massimo Costanza, Pietro Luigi Poliani, Elena Fontana, Manuela Cominelli, Gabriella Abolafio, Lawrence Steinman, Rosetta Pedotti
OBJECTIVE: To investigate the effects of targeting the high-affinity receptor for immunoglobulin E (FcεRI), that plays a central role in allergic responses and is constitutively expressed on mast cells and basophils, in clinical disease and autoimmune T-cell response in experimental MS. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein 35-55. Anti-FcεRI α-chain antibody was administered intraperitoneally...
May 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28611775/inhibition-of-myeloid-differentiation-factor-88-reduces-human-and-mouse-t-cell-interleukin-17-and-ifn%C3%AE-production-and-ameliorates-experimental-autoimmune-encephalomyelitis-induced-in-mice
#18
Shira Dishon, Shmuel J Cohen, Irun R Cohen, Gabriel Nussbaum
Myeloid differentiation factor 88 (MyD88) recruits signaling proteins to the intracellular domain of receptors belonging to the toll-like/interleukin-1 (IL-1) receptor superfamily. Mice lacking MyD88 are highly susceptible to infectious diseases, but tend to resist experimentally induced autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE) and manifest diminished allograft rejection. We reasoned that inhibition of MyD88 should influence the cytokine profile of responding T cells by blocking costimulatory molecule expression by antigen-presenting cells (APCs) and by inhibiting T-cell responses to IL-18...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28607752/enhanced-disease-reduction-using-clozapine-an-atypical-antipsychotic-agent-and-glatiramer-acetate-combination-therapy-in-experimental-autoimmune-encephalomyelitis
#19
Laura K Green, Pirooz Zareie, Nikki Templeton, Robert A Keyzers, Bronwen Connor, Anne Camille La Flamme
BACKGROUND: Atypical antipsychotic agents (AAP) alleviate the symptoms of severe mental health disorders, such as schizophrenia, by antagonizing dopamine and serotonin receptors. Recently, AAP have also been shown to exhibit immunomodulatory properties in the central nervous system (CNS). OBJECTIVE: Building on research which demonstrated the ability of the AAP risperidone and clozapine to modify the disease course of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), we aimed to more fully investigate the potential of clozapine as a possible treatment for MS...
January 2017: Multiple Sclerosis Journal—Experimental, Translational and Clinical
https://www.readbyqxmd.com/read/28607749/an-essential-role-of-virus-infected-b-cells-in-the-marmoset-experimental-autoimmune-encephalomyelitis-model
#20
REVIEW
Bert A 't Hart, Yolanda S Kap
Infection with Epstein-Barr virus (EBV) has been associated with an enhanced risk of genetically susceptible individuals to develop multiple sclerosis (MS). However, an explanation for the contrast between the high EBV infection prevalence (60-90%) and the low MS prevalence (0.1%) eludes us. Here we propose a new concept for the EBV-MS association developed in the experimental autoimmune encephalomyelitis model in marmoset monkeys, which are naturally infected with the EBV-related γ1-herpesvirus CalHV3. The data indicate that the infection of B cells with a γ1-herpesvirus endows them with the capacity to activate auto-aggressive CD8+ T cells specific for myelin oligodendrocyte glycoprotein...
January 2017: Multiple Sclerosis Journal—Experimental, Translational and Clinical
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