scholarly journals Therapeutic effect of nucleoside analogs on experimental autoimmune encephalomyelitis in dark agouti rats

2006 ◽  
Vol 58 (1) ◽  
pp. 13-20 ◽  
Author(s):  
Danijela Stojkov ◽  
Irena Lavrnja ◽  
Sanja Subasic ◽  
Ivana Bjelobaba ◽  
Sanja Pekovic ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Clinical Symptoms ◽  
Combined Treatment ◽  
Nucleoside Analogs ◽  
Dark Agouti ◽  
Autoimmune Encephalomyelitis ◽  
Additive Action ◽  
Experimental Autoimmune

Experimental autoimmune encephalomyelitis (EAE) is a commonly used animal model of the human neurological disorder multiple sclerosis. The purpose of the present study was to investigate the effect of combined treatment with two nucleoside analogs, ribavirin and tiazofurin, on development of EAE actively induced in highly susceptible dark agouti rats. The obtained results showed that ribavirin and tiazofurin applied either separately or in combination from the onset of the firstsymptoms of EAE after its induction (therapeutic treatment) significantly suppressed EAE?s clinical symptoms. However, the most pronounced effect was gained with combined treatment, probably as a result of synergistic/additive action.

AIM2 inflammasome activation in astrocytes occurs during the late phase of EAE

2021 ◽  
Author(s):  
William E. Barclay ◽  
M. Elizabeth Deerhake ◽  
Makoto Inoue ◽  
Toshiaki Nonaka ◽  
Kengo Nozaki ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Animal Model ◽  
Cell Death ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammasome Activation ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Experimental Autoimmune

ABSTRACTInflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity against pathogens and inflammatory responses through their effector cytokines, IL-1β and IL-18. Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are such autoimmune conditions influenced by inflammasomes. Despite work investigating inflammasomes during EAE, little remains known concerning the role of inflammasomes in the central nervous system (CNS) during the disease. Here we use multiple genetically modified mouse models to monitor activated inflammasomes in situ based on ASC oligomerization in the spinal cord. Using inflammasome reporter mice, we found heightened inflammasome activation in astrocytes after the disease peak. In contrast, microglia and CNS-infiltrated myeloid cells had few activated inflammasomes in the CNS during EAE. Astrocyte inflammasome activation was dependent on AIM2, but low IL-1β expression and no significant signs of cell death were found in astrocytes during EAE. Thus, the AIM2 inflammasome activation in astrocytes may have a distinct role from traditional inflammasome-mediated inflammation.SIGNIFICANCE STATEMENTInflammasome activation in the peripheral immune system is pathogenic in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, inflammasome activity in the central nervous system (CNS) is largely unexplored. Here, we used genetically modified mice to determine inflammasome activation in the CNS during EAE. Our data indicated heightened AIM2 inflammasome activation in astrocytes after the disease peak. Unexpectedly, neither CNS-infiltrated myeloid cells nor microglia were the primary cells with activated inflammasomes in SC during EAE. Despite AIM2 inflammasome activation, astrocytes did not undergo apparent cell death and produced little of the proinflammatory cytokine, IL-1β, during EAE. This study showed that CNS inflammasome activation occurs during EAE without associating with IL-1β-mediated inflammation.

scholarly journals Environmental enrichment alleviates the deleterious effects of stress in experimental autoimmune encephalomyelitis

2020 ◽  
Vol 6 (4) ◽  
pp. 205521732095980
Author(s):  
Antoine Philippe Fournier ◽  
Erwan Baudron ◽  
Isabelle Wagnon ◽  
Philippe Aubert ◽  
Denis Vivien ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Environmental Enrichment ◽  
Acute Stress ◽  
Stressful Events ◽  
Autoimmune Encephalomyelitis ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients ◽  
Experimental Autoimmune

Background Clinical observations support the hypothesis that stressful events increase relapse occurrence in multiple sclerosis patients, while stress-reduction strategies can modulate this effect. However, a direct cause-effect relationship between stress level and relapse cannot be firmly established from these data. Objectives The purpose of this work was to address whether modulation of stress could interfere with symptom relapse in an animal model of multiple sclerosis with relapsing-remitting course. Methods Mice bred in standard or enriched environment were subjected to repeated acute stress during the remission phase of relapsing-remitting PLP-induced experimental autoimmune encephalomyelitis. Results We report that repeated acute stress induced a twofold increase in relapse incidence in experimental autoimmune encephalomyelitis. On the other hand, environmental enrichment reduced relapse incidence and severity, and reversed the effects of repeated acute stress. Conclusion These data provide the platform for further studies on the biological processes that link stress and multiple sclerosis relapses in a suitable animal model.

scholarly journals Suppression of experimental autoimmune encephalomyelitis using estrogen receptor-selective ligands

2005 ◽  
Vol 185 (2) ◽  
pp. 243-252 ◽  
Author(s):  
M Merle Elloso ◽  
Kristen Phiel ◽  
Ruth A Henderson ◽  
Heather A Harris ◽  
Steven J Adelman
Keyword(s):  
Multiple Sclerosis ◽  
Estrogen Receptor ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Immune Responses ◽  
Clinical Symptoms ◽  
Protective Effects ◽  
Autoimmune Encephalomyelitis ◽  
Selective Agonist ◽  
Selective Ligands ◽  
Experimental Autoimmune

Estrogens have been shown to modulate disease activity in experimental autoimmune encephalomyelitis (EAE), the mouse model for multiple sclerosis. Consistent with these findings, the severity of disease is reduced in pregnant women with multiple sclerosis when levels of estrogens are high. Estrogens bind to two known estrogen receptors (ER), ERα and ERβ. The relative contribution of these receptors to estrogen-mediated suppression of EAE was explored using ER-selective ligands. The ER antagonist ICI 182 780 reversed the suppressive effects of 17β-estradiol (E2), demonstrating that the protective effects of E2 on disease are dependent upon ER signaling. Treatment of SJL mice with the ERα-selective agonist proteolipid protein (PPT) prior to the induction of disease resulted in suppression of clinical symptoms of disease, whereas treatment with an ERβ-selective agonist (WAY-202041) had no effect. Treatment of mice with PLP peptide 139–151 (PPT) was also associated with decreased immune responses associated with disease. Consistent with its lack of effect on disease, the ERβ agonist had minimal effects on immune responses. The use of selective estrogen receptor modulators (SERMs) in this model was also explored, and we show that raloxifene and WAY-138923 were also effective in suppressing disease. These results demonstrate the beneficial effects of estrogen receptor ligands, in particular ERα-selective ligands, and may have implications in the development of therapeutic strategies for multiple sclerosis.

scholarly journals Antiinflammatory Properties of a Plant-Derived Nonsteroidal, Dissociated Glucocorticoid Receptor Modulator in Experimental Autoimmune Encephalomyelitis

2009 ◽  
Vol 94 (12) ◽  
pp. 5184-5184
Author(s):  
Geert van Loo ◽  
Mozes Sze ◽  
Nadia Bougarne ◽  
Jelle Praet ◽  
Conor McGuire ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Glucocorticoid Receptor ◽  
Clinical Symptoms ◽  
Neuronal Damage ◽  
Nuclear Factor Κb ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Nuclear Factor ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Abstract Compound A (CpdA), a plant-derived phenyl aziridine precursor, was recently characterized as a fully dissociated nonsteroidal antiinflammatory agent, acting via activation of the glucocorticoid receptor, thereby down-modulating nuclear factor-κB-mediated transactivation, but not supporting glucocorticoid response element-driven gene expression. The present study demonstrates the effectiveness of CpdA in inhibiting the disease progress in experimental autoimmune encephalomyelitis (EAE), a well-characterized animal model of multiple sclerosis. CpdA treatment of mice, both early and at the peak of the disease, markedly suppressed the clinical symptoms of EAE induced by myelin oligodendrocyte glycoprotein peptide immunization. Attenuation of the clinical symptoms of EAE by CpdA was accompanied by reduced leukocyte infiltration in the spinal cord, reduced expression of inflammatory cytokines and chemokines, and reduced neuronal damage and demyelination. In vivo CpdA therapy suppressed the encephalogenicity of myelin oligodendrocyte glycoprotein peptide-specific T cells. Moreover, CpdA was able to inhibit TNF- and lipopolysaccharide-induced nuclear factor-κB activation in primary microglial cells in vitro, in a differential mechanistic manner as compared with dexamethasone. Finally, in EAE mice the therapeutic effect of CpdA, in contrast to that of dexamethasone, occurred in the absence of hyperinsulinemia and in the absence of a suppressive effect on the hypothalamic-pituitary-adrenal axis. Based on these results, we propose CpdA as a compound with promising antiinflammatory characteristics useful for therapeutic intervention in multiple sclerosis and other neuroinflammatory diseases.

Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis

2016 ◽  
Vol 7 (3) ◽  
pp. 363-373 ◽  
Author(s):  
S. Stanisavljević ◽  
J. Lukić ◽  
M. Momčilović ◽  
M. Miljković ◽  
B. Jevtić ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Gut Microbiota ◽  
Lymphoid Tissue ◽  
Dark Agouti ◽  
Interleukin 17 ◽  
Mesenteric Lymph Nodes ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Gut microbiota and gut-associated lymphoid tissue have been increasingly appreciated as important players in pathogenesis of various autoimmune diseases, including multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis that can be induced with an injection of spinal cord homogenate emulsified in complete Freund’s adjuvant in Dark Agouti (DA) rats, but not in Albino Oxford (AO) rats. In this study, mesenteric lymph nodes (MLN), Peyer’s patches (PP) and gut microbiota were analysed in these two rat strains. There was higher proportion of CD4+ T cells and regulatory T cells in non-immunised DA rats in comparison to AO rats. Also, DA rat MLN and PP cells were higher producers of pro-inflammatory cytokines interferon-γ and interleukin-17. Finally, microbial analyses showed that uncultivated species of Turicibacter and Atopostipes genus were exclusively present in AO rats, in faeces and intestinal tissue, respectively. Thus, it is clear that in comparison of an EAE-susceptible with an EAE-resistant strain of rats, various discrepancies at the level of gut associated lymphoid tissue, as well as at the level of gut microbiota can be observed. Future studies should determine if the differences have functional significance for EAE pathogenesis.

scholarly journals NLRP3 Inflammasome and MS/EAE

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Makoto Inoue ◽  
Mari L. Shinohara
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Immune System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Nlrp3 Inflammasome ◽  
Innate Immune System ◽  
Innate Immune ◽  
Autoimmune Encephalomyelitis ◽  
Danger Signals ◽  
Experimental Autoimmune

Inflammasomes are cytosolic sensors that detect pathogens and danger signals in the innate immune system. The NLRP3 inflammasome is currently the most fully characterized inflammasome and is known to detect a wide array of microbes and endogenous damage-associated molecules. Possible involvement of the NLRP3 inflammasome (or inflammasomes) in the development of multiple sclerosis (MS) was suggested in a number of studies. Recent studies showed that the NLRP3 inflammasome exacerbates experimental autoimmune encephalomyelitis (EAE), an animal model of MS, although EAE can also develop without the NLRP3 inflammasome. In this paper, we discuss the NLRP3 inflammasome in MS and EAE development.

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