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Systemic sclerosis animal model

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https://www.readbyqxmd.com/read/28619000/astrocytes-pathology-in-als-a-potential-therapeutic-target
#1
Sonja Johann
The mechanisms underlying neurodegeneration in amyotrophic lateral sclerosis (ALS) are multifactorial and include genetic and environmental factors. Nowadays, it is well accepted that neuronal loss is driven by non-cell autonomous toxicity. Non-neuronal cells, such as astrocytes, have been described to significantly contribute to motoneuron cell death and disease progression in cell culture experiments and animal models of ALS. Astrocytes are essential for neuronal survival and function by regulating neurotransmitter and ion homeostasis, immune response, blood flow and glucose uptake, antioxidant defence and growth factor release...
June 15, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28618115/iron-sulfur-glutaredoxin-2-protects-oligodendrocytes-against-damage-induced-by-nitric-oxide-release-from-activated-microglia
#2
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/28617951/altered-expression-of-igf-i-system-in-neurons-of-the-inflamed-spinal-cord-during-acute-experimental-autoimmune-encephalomyelitis
#3
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/28607752/enhanced-disease-reduction-using-clozapine-an-atypical-antipsychotic-agent-and-glatiramer-acetate-combination-therapy-in-experimental-autoimmune-encephalomyelitis
#4
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/28604632/experimental-autoimmune-encephalomyelitis-eae-induced-elevated-expression-of-the-e1-isoform-of-methyl-cpg-binding-protein-2-mecp2e1-implications-in-multiple-sclerosis-ms-induced-neurological-disability-and-associated-myelin-damage
#5
Tina Khorshid Ahmad, Ting Zhou, Khaled AlTaweel, Claudia Cortes, Ryan Lillico, Ted Martin Lakowski, Kiana Gozda, Michael Peter Namaka
Multiple sclerosis (MS) is a chronic neurological disease characterized by the destruction of central nervous system (CNS) myelin. At present, there is no cure for MS due to the inability to repair damaged myelin. Although the neurotrophin brain derived neurotrophic factor (BDNF) has a beneficial role in myelin repair, these effects may be hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2) called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE)-induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the myelin repair process by repressing BDNF expression...
June 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28602360/the-role-of-platelets-in-autoimmunity-vasculopathy-and-fibrosis-implications-for-systemic-sclerosis
#6
REVIEW
Konstantinos Ntelis, Elena E Solomou, Lazaros Sakkas, Stamatis-Nick Liossis, Dimitrios Daoussis
INTRODUCTION: Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, autoimmunity, and widespread dermal and visceral fibrosis. This article summarizes the current knowledge about the potential contribution of platelets in the disease process and the rationale of targeting platelets as an adjunct treatment for SSc. METHODS: We performed an electronic search (Medline) using the keywords platelets, systemic sclerosis, autoimmunity, fibrosis, Raynaud, and pulmonary arterial hypertension...
May 23, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28601278/laquinimod-has-no-effects-on-brain-volume-or-cellular-cns-composition-in-the-f1-3xtg-ad-c3h-mouse-model-of-alzheimer-s-disease
#7
Rehana Z Hussain, William A Miller-Little, Doris Lambracht-Washington, Tom C Jaramillo, Masaya Takahashi, Shanrong Zhang, Min Fu, Gary R Cutter, Liat Hayardeny, Craig M Powell, Roger N Rosenberg, Olaf Stüve
BACKGROUND: Laquinimod is an anti-inflammatory agent with good central nervous system (CNS) bioavailability, and neuroprotective and myelorestorative properties. A clinical trial in patients with multiple sclerosis demonstrated that laquinimod significantly reduced loss of brain volume. The cellular substrate or molecular events underlying that treatment effect are unknown. In this study, we aimed to explore laquinimod's potential effects on brain volume, animal behavior, cellular numbers and composition of CNS-intrinsic cells and mononuclear cells within the CNS, amyloid beta (Aβ) accumulation and tau phosphorylation in the F1 3xTg-AD/C3H mouse model of Alzheimer's disease...
August 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28600752/rapamycin-ameliorates-experimental-autoimmune-encephalomyelitis-by-suppressing-the-mtor-stat3-pathway
#8
Huiqing Hou, Jun Miao, Runjing Cao, Mei Han, Yafei Sun, Xiaoqian Liu, Li Guo
Rapamycin is a new immunosuppressant that has a primarily anti-inflammatory effect and selectively inhibits the activation of T helper (Th)-cell subsets. It is widely used to treat autoimmune disease. We studied the mechanism of rapamycin action against experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, a classic animal model of multiple sclerosis. Rapamycin significantly inhibited the development of EAE by decreasing both clinical scores and inflammatory cell infiltration into the spinal cord...
May 30, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28599652/regulatory-t-cells-in-multiple-sclerosis-and-myasthenia-gravis
#9
REVIEW
K M Danikowski, S Jayaraman, B S Prabhakar
Multiple sclerosis (MS) is a chronic debilitating disease of the central nervous system primarily mediated by T lymphocytes with specificity to neuronal antigens in genetically susceptible individuals. On the other hand, myasthenia gravis (MG) primarily involves destruction of the neuromuscular junction by antibodies specific to the acetylcholine receptor. Both autoimmune diseases are thought to result from loss of self-tolerance, which allows for the development and function of autoreactive lymphocytes. Although the mechanisms underlying compromised self-tolerance in these and other autoimmune diseases have not been fully elucidated, one possibility is numerical, functional, and/or migratory deficits in T regulatory cells (Tregs)...
June 9, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28583039/experimental-models-of-autoimmune-demyelinating-diseases-in-nonhuman-primates
#10
Lev Stimmer, Claire-Maëlle Fovet, Ché Serguera
Human idiopathic inflammatory demyelinating diseases (IIDD) are a heterogeneous group of autoimmune inflammatory and demyelinating disorders of the central nervous system (CNS). These include multiple sclerosis (MS), the most common chronic IIDD, but also rarer disorders such as acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica (NMO). Great efforts have been made to understand the pathophysiology of MS, leading to the development of a few effective treatments. Nonetheless, IIDD still require a better understanding of the causes and underlying mechanisms to implement more effective therapies and diagnostic methods...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28576706/rhigm22-enhances-remyelination-in-the-brain-of-the-cuprizone-mouse-model-of-demyelination
#11
Ariana P Mullin, Charlene Cui, Yu Wang, Jing Wang, Erika Troy, Anthony O Caggiano, Tom J Parry, Raymond W Colburn, Elias Pavlopoulos
Failure of oligodendrocyte precursor cells (OPCs) to differentiate and remyelinate axons is thought to be a major cause of the limited ability of the central nervous system to repair plaques of immune-mediated demyelination in multiple sclerosis (MS). Current therapies for MS aim to lessen the immune response in order to reduce the frequency and severity of attacks, but these existing therapies do not target remyelination or stimulate repair of the damaged tissue. Thus, the promotion of OPC differentiation and remyelination is potentially an important therapeutic goal...
May 30, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28557239/the-neuroprotective-effect-of-mesenchymal-stem-cells-on-an-experimentally-induced-model-for-multiple-sclerosis-in-mice
#12
Marwa M Mahfouz, Rania M Abdelsalam, Marwa A Masoud, Hanaa A Mansour, Omar A Ahmed-Farid, Sanaa A Kenawy
Multiple sclerosis (MS) is a chronic autoimmune demyelinating neurodegenerative central nervous system disorder. The aim of the present study was to investigate the prophylactic effect exerted by the one-time intraperitoneal injection of mesenchymal stem cells (MSCs) 1 × 10(6) and 14-day intraperitoneal injection of methylprednisolone (MP) 40 mg/kg in an experimental autoimmune encephalomyelitis (EAE). EAE was induced by intradermal injection of rat spinal cord homogenate with complete Freund's adjuvant in Swiss mice...
May 29, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28556916/intestinal-dysbiosis-and-probiotic-applications-in-autoimmune-diseases
#13
REVIEW
Gislane Lelis Vilela de Oliveira, Aline Zazeri Leite, Bruna Stevanato Higuchi, Marina Ignácio Gonzaga, Vânia Sammartino Mariano
In humans, a complex interaction between the host immune system and commensal microbiota is required to maintain gut homeostasis. In this symbiotic relationship, the microbiota provides carbohydrate fermentation and digestion, vitamin synthesis, and gut-associated lymphoid tissue development, as well as prevents colonization by pathobionts, whereas the host offers a niche and nutrients for the survival of the microbiota. However, when this mutualistic relationship is compromised and an altered interaction between immune cells and microorganisms occurs, the gut microbiota may cause or contribute to the establishment of infectious diseases and trigger autoimmune diseases...
May 29, 2017: Immunology
https://www.readbyqxmd.com/read/28552332/1-25-dihydroxyvitamin-d3-suppressed-experimental-autoimmune-encephalomyelitis-through-both-immunomodulation-and-oligodendrocyte-maturation
#14
Hasti Atashi Shirazi, Javad Rasouli, Bogoljub Ciric, Danmeng Wei, Abdolmohamad Rostami, Guang-Xian Zhang
1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has recently been found to have the anti-inflammatory potential to suppress experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis; however, its direct effect on neural cells is not clear. In the current study we show that 1,25(OH)2D3 treatment effectively suppressed clinical signs of ongoing EAE and reduced inflammation and demyelination scores in the central nervous system (CNS). The treatment significantly decreased production/expression of pro-inflammatory cytokines IFN-γ, GM-CSF and IL-17A, while it increased anti-inflammatory cytokines IL-4 and IL-10...
May 25, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28552054/neurotoxicity-of-insecticides
#15
Julien Cassereau, Marc Ferré, Arnaud Chevrollier, Philippe Codron, Christophe Verny, Chadi Homedan, Guy Lenaers, Vincent Procaccio, Pascale May-Panloup, Pascal Reynier
BACKGROUND: Human exposure to insecticides raises serious public health concerns worldwide. Insecticides constitute a wide-ranging heterogeneous group of chemicals, most of which target the nervous system and disrupt neurometabolism and/or neurotransmission. Although the acute effects of insecticide poisoning in humans are well documented, the chronic and long-term effects remain difficult to investigate. OBJECTIVES AND METHOD: We sought to review the present state-of-knowledge of acute, chronic, neurodevelopmental and neurological consequences of human exposure to insecticides...
May 26, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28545512/tie2-as-a-novel-key-factor-of-microangiopathy-in-systemic-sclerosis
#16
Falk Moritz, Janine Schniering, Jörg H W Distler, Renate E Gay, Steffen Gay, Oliver Distler, Britta Maurer
BACKGROUND: The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling is also attenuated by soluble Tie2 (sTie2), the extracellular domain of the receptor, which is shed upon stimulation with VEGF. Herein, we investigate the role of Ang/Tie2 in the peripheral vasculopathy in systemic sclerosis (SSc) including animal models...
May 25, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28542521/regeneration-of-myelin-sheaths-of-normal-length-and-thickness-in-the-zebrafish-cns-correlates-with-growth-of-axons-in-caliber
#17
Marja J Karttunen, Tim Czopka, Marieke Goedhart, Jason J Early, David A Lyons
Demyelination is observed in numerous diseases of the central nervous system, including multiple sclerosis (MS). However, the endogenous regenerative process of remyelination can replace myelin lost in disease, and in various animal models. Unfortunately, the process of remyelination often fails, particularly with ageing. Even when remyelination occurs, it is characterised by the regeneration of myelin sheaths that are abnormally thin and short. This imperfect remyelination is likely to have implications for the restoration of normal circuit function and possibly the optimal metabolic support of axons...
2017: PloS One
https://www.readbyqxmd.com/read/28536579/peripherally-induced-regulatory-t-cells-recruited-protectors-of-the-central-nervous-system-against-autoimmune-neuroinflammation
#18
REVIEW
Andrew Jones, Daniel Hawiger
Defects in regulatory T cells (Treg cells) aggravate multiple sclerosis (MS) after its onset and the absence of Treg cell functions can also exacerbate the course of disease in an animal model of MS. However, autoimmune neuroinflammation in many MS models can be acutely provoked in healthy animals leading to an activation of encephalitogenic T cells despite the induction of immune tolerance in the thymus including thymically produced (t)Treg cells. In contrast, neuroinflammation can be ameliorated or even completely prevented by the antigen-specific Treg cells formed extrathymically in the peripheral immune system (pTreg cells) during tolerogenic responses to relevant neuronal antigens...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28499934/matrine-promotes-oligodendrocyte-development-in-cns-autoimmunity-through-the-pi3k-akt-signaling-pathway
#19
Shu-Qing Liu, Ming-Liang Zhang, HUi-Jun Zhang, Fang-Zhou Liu, Rao-Juan Chu, Guang-Xian Zhang, Lin Zhu
AIMS: Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, has been recently found to be beneficial in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, mainly through its anti-inflammatory effect. In the present study, we tested the effect of MAT on ongoing EAE and defined possible mechanisms underlying its effects on myelination and oligodendrocytes. MAIN METHODS: EAE was induced in C57BL/6 mice and MAT treatment was started at disease onset...
July 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28488090/pathogenesis-of-systemic-sclerosis-current-concept-and-emerging-treatments
#20
REVIEW
Masutaka Furue, Chikage Mitoma, Hiroki Mitoma, Gaku Tsuji, Takahito Chiba, Takeshi Nakahara, Hiroshi Uchi, Takafumi Kadono
Systemic sclerosis (SSc) is an intractable multifaceted disease with high mortality. Although its pathogenesis is not fully understood, recent studies have advanced our knowledge on SSc. The cardinal pathological features of SSc are autoimmunity, vasculopathy, and fibrosis. The B cells in SSc are constitutively activated and lead to the production of a plethora of autoantibodies, such as anti-topoisomerase I and anti-centromere antibodies. In addition to these autoantibodies, which are valuable for diagnostic criteria or biomarkers, many other autoantibodies targeting endothelial cells, including endothelin type A receptor and angiotensin II type I receptor, are known to be functional and induce activation or apoptosis of endothelial cells...
May 9, 2017: Immunologic Research
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