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experimental autoimmune encephalomyelitis

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https://www.readbyqxmd.com/read/27920149/mir-142-3p-is-a-key-regulator-of-il-1%C3%AE-dependent-synaptopathy-in-neuroinflammation
#1
Georgia Mandolesi, Francesca De Vito, Alessandra Musella, Antonietta Gentile, Silvia Bullitta, Diego Fresegna, Helena Sepman, Claudio Di Sanza, Nabila Haji, Francesco Mori, Fabio Buttari, Emerald Perlas, Maria Teresa Ciotti, Eran Hornstein, Irene Bozzoni, Carlo Presutti, Diego Centonze
: MicroRNAs (miRNA) play an important role in posttranscriptional gene regulation of several physiological and pathological processes. In multiple sclerosis (MS), a chronic inflammatory and degenerative disease of the CNS, and in its mouse model, the experimental autoimmune encephalomyelitis (EAE), miRNA dysregulation has been mainly related to immune system dysfunction and white matter pathology. However, little is known about their role in grey matter pathology. Here, we explored miRNA involvement in the inflammation-driven alterations of synaptic structure and function, collectively known as synaptopathy, a neuropathological process contributing to excitotoxic neurodegeneration in MS/EAE...
December 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27918427/prolactin-friend-or-foe-in-central-nervous-system-autoimmune-inflammation
#2
REVIEW
Massimo Costanza, Rosetta Pedotti
The higher prevalence of multiple sclerosis (MS) in females, along with the modulation of disease activity observed during pregnancy and the post-partum period, has suggested a hormonal influence in MS. Even if prolactin (PRL) does not belong to the sex hormones family, its crucial role in female reproduction and lactation has prompted great efforts to understand if PRL could represent a gender factor in the pathogenesis of MS and experimental autoimmune encephalomyelitis (EAE), the animal model for this disease...
December 2, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27917173/live-imaging-of-immune-responses-in-experimental-models-of-multiple-sclerosis
#3
REVIEW
Barbara Rossi, Gabriela Constantin
Experimental autoimmune encephalomyelitis (EAE) is the most common animal model of multiple sclerosis (MS), a chronic inflammatory autoimmune disease of the central nervous system (CNS) characterized by multifocal perivascular infiltrates that predominantly comprise lymphocytes and macrophages. During EAE, autoreactive T cells first become active in the secondary lymphoid organs upon contact with antigen-presenting cells (APCs), and then gain access to CNS parenchyma, through a compromised blood-brain barrier, subsequently inducing inflammation and demyelination...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27912762/regulation-of-effector-function-of-cns-autoreactive-cd4-t-cells-through-inhibitory-receptors-and-il-7r%C3%AE
#4
Patrick K Nuro-Gyina, Elizabeth L Rieser, Marissa C Granitto, Wei Pei, Yue Liu, Priscilla W Lee, Saba Aqel, Jian Zhang, Amy E Lovett-Racke, Michael K Racke, Yuhong Yang
BACKGROUND: Multiple sclerosis (MS) is a chronic CNS autoimmune disease characterized by inflammation, demyelination, and neuronal degeneration, where myelin-specific CD4 T cells play critical roles in the formation of acute MS lesions and disease progression. The suppression of IL-7Rα expression and the upregulation of inhibitory receptors (PD-1, etc.) are essential parts of the cell-intrinsic immunosuppressive program regulating T effector functions to prevent autoimmunity. However, little is known on the factors regulating IL-7Rα/PD-1 balance in myelin-specific CD4 T effector/memory cells during the development of CNS autoimmunity...
December 3, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27910985/uvb-radiation-vitamin-d-and-multiple-sclerosis
#5
H F DeLuca, L Plum
Acheson et al. (1960) observed an inverse relationship between sunlight exposure and the incidence of Multiple Sclerosis (MS). This led to the suggestion that increased levels of vitamin D caused by sunlight in some way suppresses MS. Further, super physiological doses of the metabolically active metabolite of vitamin D, i.e. 1α,25 dihydroxy vitamin D suppresses the animal model of MS i.e. experimental autoimmune encephalomyelitis (EAE). However, this response was accompanied by hypercalcemia. Hypercalcemia itself can suppress EAE...
December 2, 2016: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/27909192/the-more-the-merrier-scoring-statistics-and-animal-welfare-in-experimental-autoimmune-encephalomyelitis
#6
Pushpalatha Palle, Filipa M Ferreira, Axel Methner, Thorsten Buch
Experimental autoimmune encephalomyelitis (EAE) is a frequently used animal model for the investigation of autoimmune processes in the central nervous system. As such, EAE is useful for modelling certain aspects of multiple sclerosis, a human autoimmune disease that leads to demyelination and axonal destruction. It is an important tool for investigating pathobiology, identifying drug targets and testing drug candidates. Even though EAE is routinely used in many laboratories and is often part of the routine assessment of knockouts and transgenes, scoring of the disease course has not become standardized in the community, with at least 83 published scoring variants...
December 2016: Laboratory Animals
https://www.readbyqxmd.com/read/27908754/cyclic-citrullinated-mbp87-99-peptide-stimulates-t-cell-responses-implications-in-triggering-disease
#7
Vasso Apostolopoulos, George Deraos, Minos-Timotheos Matsoukas, Stephanie Day, Lily Stojanovska, Theodore Tselios, Maria-Eleni Androutsou, John Matsoukas
Amino acid mutations to agonist peptide epitopes of myelin proteins have been used to modulate immune responses and experimental autoimmune encephalomyelitis (EAE, animal model of multiple sclerosis). Such amino acid alteration are termed, altered peptide ligands (APL). We have shown that the agonist myelin basic protein (MBP) 87-99 epitope (MBP87-99) with crucial T cell receptor (TCR) substitutions at positions 91 and 96 (K(91),P(96) (TCR contact residues) to R(91),A(96); [R(91),A(96)]MBP87-99) results in altered T cell responses and inhibits EAE symptoms...
November 19, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27908532/ram-589-555-a-new-polymerase-1-inhibitor-as-innovative-targeted-treatment-for-multiple-sclerosis
#8
A Achiron, R Zilkha-Falb, R Mashiach, M Gurevich
Targeting Polymerase-1 (POL1) transcription machinery is a new strategy for suppression of multiple sclerosis (MS) disease activity that is based on suppression of ribosomal biogenesis and subsequent activation of apoptosis. We developed an oral POL1 inhibiting compound RAM-589.555, that suppress ribosomal biogenesis as an innovative therapeutic approach to ameliorate MS. RAM-589.555 shows high permeability, specificity to POL1 pathway, ability to induce apoptosis and to inhibit proliferation and viability of activated lymphocytes both in-vitro and in-vivo...
November 17, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27907119/gray-matter-hypoxia-in-the-brain-of-the-experimental-autoimmune-encephalomyelitis-model-of-multiple-sclerosis
#9
Thomas W Johnson, Ying Wu, Nabeela Nathoo, James A Rogers, V Wee Yong, Jeff F Dunn
BACKGROUND: Multiple sclerosis (MS) has a significant inflammatory component and may have significant gray matter (GM) pathophysiology. Brain oxygenation is a sensitive measurement of the balance between metabolic need and oxygen delivery. There is evidence that inflammation and hypoxia are interdependent. In this paper, we applied novel, implanted PO2 sensors to measure hypoxia in cortical and cerebellar GM, in an inflammation-induced mouse model of MS. OBJECTIVE: Quantify oxygenation in cortical and cerebellar GM in the awake, unrestrained experimental autoimmune encephalomyelitis (EAE) mouse model and to relate the results to symptom level and disease time-course...
2016: PloS One
https://www.readbyqxmd.com/read/27904492/hydroxycitric-acid-ameliorates-inflammation-and-oxidative-stress-in-mouse-models-of-multiple-sclerosis
#10
Mahdi Goudarzvand, Sanaz Afraei, Somaye Yaslianifard, Saleh Ghiasy, Ghazal Sadri, Mustafa Kalvandi, Tina Alinia, Ali Mohebbi, Reza Yazdani, Shahin Khadem Azarian, Abbas Mirshafiey, Gholamreza Azizi
Hydroxycitric acid (HCA) is derived primarily from the Garcinia plant and is widely used for its anti-inflammatory effects. Multiple sclerosis can cause an inflammatory demyelination and axonal damage. In this study, to validate the hypothesis that HCA exhibits therapeutic effects on multiple sclerosis, we established female C57BL/6 mouse models of multiple sclerosis, i.e., experimental autoimmune encephalomyelitis, using Complete Freund's Adjuvant (CFA) emulsion containing myelin oligodendrocyte glycoprotein (35-55)...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27903258/catwalk-gait-analysis-in-a-rat-model-of-multiple-sclerosis
#11
Sabine Herold, Prateek Kumar, Klaus Jung, Irina Graf, Henrike Menkhoff, Xenia Schulz, Mathias Bähr, Katharina Hein
BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for multiple sclerosis. The characteristic feature of the MOG-EAE model in Brown Norway rats is consistent involvement of the spinal cord resulting in limb paresis. The aim of the study was to investigate whether early subclinical gait abnormalities are present in this animal model and can be detected by CatWalk XT, a fully automated gait analysis system...
November 30, 2016: BMC Neuroscience
https://www.readbyqxmd.com/read/27890794/target-regulation-of-pi3k-akt-mtor-pathway-by-cannabidiol-in-treatment-of-experimental-multiple-sclerosis
#12
Sabrina Giacoppo, Federica Pollastro, Gianpaolo Grassi, Placido Bramanti, Emanuela Mazzon
This study was aimed to investigate whether treatment with purified cannabidiol (CBD) may counteract the development of experimental multiple sclerosis (MS), by targeting the PI3K/Akt/mTOR pathway. Although the PI3K/Akt/mTOR pathway was found to be activated by cannabinoids in several immune and non-immune cells, currently, there is no data about the effects of CBD in the PI3K/Akt/mTOR activity in MS. Experimental Autoimmune Encephalomyelitis (EAE), the most common model of MS, was induced in C57BL/6 mice by immunization with myelin oligodendroglial glycoprotein peptide (MOG)35-55...
November 25, 2016: Fitoterapia
https://www.readbyqxmd.com/read/27884750/methylprednisolone-improves-lactate-metabolism-through-reduction-of-elevated-serum-lactate-in-rat-model-of-multiple-sclerosis
#13
Majid Ghareghani, Amir Ghanbari, Shima Dokoohaki, Naser Farhadi, Seyed Mojtaba Hosseini, Reza Mohammadi, Heibatollah Sadeghi
BACKGROUND: Some studies have demonstrated elevated concentrations of lactate both in the cerebrospinal fluid (CSF) and blood samples of multiple sclerosis (MS) patients as a pathological condition. We designed an experimental study first to investigate the serum level of lactate as a biomarker of MS progression and also to investigate the effect of methylprednisolone on serum lactate. METHODS: Experimental autoimmune encephalomyelitis (EAE) was inducted in Lewis rats, and then rats were treated intraperitoneally with methylprednisolone (30mg/kg/d), at the disease onset, and the clinical scores were recorded...
November 21, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27882538/gene-therapy-with-mesenchymal-stem-cells-expressing-ifn%C3%A3-ameliorates-neuroinflammation-in-experimental-models-of-multiple-sclerosis
#14
C Marin-Bañasco, K Benabdellah, C Melero-Jerez, B Oliver, M J Pinto-Medel, I Hurtado-Guerrero, F de Castro, D Clemente, O Fernández, F Martin, L Leyva, M Suardíaz
BACKGROUND AND PURPOSE: Recombinant IFNß is one of the first line treatments in multiple sclerosis (MS), despite its lack of efficiency in some patients. In this context, mesenchymal stem cells (MSCs) represent a promising therapeutic alternative due to their immunomodulatory properties and multipotency. Moreover, taking advantage of their pathotropism ability, these cells can be genetically modified to be used as carriers for delivering or secreting therapeutic drugs into injured tissues...
November 24, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27882351/activity-of-nav1-2-promotes-neurodegeneration-in-an-animal-model-of-multiple-sclerosis
#15
Benjamin Schattling, Walid Fazeli, Birgit Engeland, Yuanyuan Liu, Holger Lerche, Dirk Isbrandt, Manuel A Friese
Counteracting the progressive neurological disability caused by neuronal and axonal loss is the major unmet clinical need in multiple sclerosis therapy. However, the mechanisms underlying irreversible neuroaxonal degeneration in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE) are not well understood. A long-standing hypothesis holds that the distribution of voltage-gated sodium channels along demyelinated axons contributes to neurodegeneration by increasing neuroaxonal sodium influx and energy demand during CNS inflammation...
November 17, 2016: JCI Insight
https://www.readbyqxmd.com/read/27876534/transcranial-magnetic-stimulation-modifies-astrocytosis-cell-density-and-lipopolysaccharide-levels-in-experimental-autoimmune-encephalomyelitis
#16
Francisco J Medina-Fernández, Evelio Luque, Macarena Aguilar-Luque, Eduardo Agüera, Montserrat Feijóo, Fe I García-Maceira, Begoña M Escribano, Álvaro Pascual-Leone, René Drucker-Colín, Isaac Túnez
AIMS: Experimental autoimmune encephalomyelitis (EAE) is considered a valid experimental model for multiple sclerosis, a chronic neuroinflammatory condition of the central nervous system. Additionally, some evidence has shown that some microbial products such as the bacterial lipopolysaccharide could lead to the activation of reactive immune cells, triggering neuroinflammation. Several studies have found that transcranial magnetic stimulation (TMS) may exert a neuroprotective effect. Therefore, we aimed to assess the effect of TMS on the neuroinflammation occurring in EAE...
November 19, 2016: Life Sciences
https://www.readbyqxmd.com/read/27872279/role-of-the-receptor-mas-in-macrophage-mediated-inflammation-in-vivo
#17
Anna Hammer, Guang Yang, Juliane Friedrich, Agnes Kovacs, De-Hyung Lee, Katharina Grave, Stefanie Jörg, Natalia Alenina, Janina Grosch, Jürgen Winkler, Ralf Gold, Michael Bader, Arndt Manzel, Lars C Rump, Dominik N Müller, Ralf A Linker, Johannes Stegbauer
Recently, an alternative renin-angiotensin system pathway has been described, which involves binding of angiotensin-(1-7) to its receptor Mas. The Mas axis may counterbalance angiotensin-II-mediated proinflammatory effects, likely by affecting macrophage function. Here we investigate the role of Mas in murine models of autoimmune neuroinflammation and atherosclerosis, which both involve macrophage-driven pathomechanisms. Mas signaling affected macrophage polarization, migration, and macrophage-mediated T-cell activation...
November 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27864936/effect-of-sphingosine-kinase-modulators-on-interleukin-1%C3%AE-release-sphingosine-1-phosphate-receptor-1-expression-and-experimental-autoimmune-encephalomyelitis
#18
Mark Barbour, Melissa McNaughton, Stephanie D Boomkamp, Neil MacRitchie, Hui-Rong Jiang, Nigel J Pyne, Susan Pyne
BACKGROUND AND PURPOSE: The sphingosine analogue, FTY720 (Gilenya(R) ) alleviates clinical disease progression in multiple sclerosis. Here we variously assessed the effects of an azide analogue of (S)-FTY720 vinylphosphonate (compound 5; a sphingosine kinase 1 activator), (R)-FTY720 methyl ether (ROMe, a sphingosine kinase 2 inhibitor) and RB-020 (a sphingosine kinase 1 inhibitor and sphingosine kinase 2 substrate) on IL-1β formation, sphingosine 1-phosphate levels and S1P1 expression...
November 16, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27856664/the-gut-brain-connection-triggering-of-brain-autoimmune-disease-by-commensal-gut-bacteria
#19
REVIEW
Hartmut Wekerle
In a transgenic model of spontaneous experimental autoimmune encephalomyelitis, autoimmune attack against the CNS requires the presence of an intact commensal gut flora. Extending this observation to human autoimmune disease, such as multiple sclerosis, we postulate that the pathogenic reaction requires the coincidence of at least three factors: a permissive genetic disposition, a pro-inflammatory intestinal microbial profile, and the accumulation of autoreactive T cells in the gut-associated lymphatic tissue...
December 2016: Rheumatology
https://www.readbyqxmd.com/read/27852330/appearance-of-claudin-5-leukocytes-in-the-central-nervous-system-during-neuroinflammation-a-novel-role-for-endothelial-derived-extracellular-vesicles
#20
Debayon Paul, Valentina Baena, Shujun Ge, Xi Jiang, Evan R Jellison, Timothy Kiprono, Dritan Agalliu, Joel S Pachter
BACKGROUND: The mechanism of leukocyte transendothelial migration (TEM) across the highly restrictive blood-brain barrier (BBB) remains enigmatic, with paracellular TEM thought to require leukocytes to somehow navigate the obstructive endothelial tight junctions (TJs). Transient interactions between TJ proteins on the respective leukocyte and endothelial surfaces have been proposed as one mechanism for TEM. Given the expanding role of extracellular vesicles (EVs) in intercellular communication, we investigated whether EVs derived from brain microvascular endothelial cells (BMEC) of the BBB may play a role in transferring a major TJ protein, claudin-5 (CLN-5), to leukocytes as a possible basis for such a mechanism during neuroinflammation...
November 16, 2016: Journal of Neuroinflammation
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