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Systemic sclerosis animal model

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https://www.readbyqxmd.com/read/29614705/identification-of-a-resilient-mouse-facial-motoneuron-population-following-target-disconnection-by-injury-or-disease
#1
Deborah O Setter, Melissa M Haulcomb, Taylor Beahrs, Rena M Meadows, Nicole D Schartz, Sara K Custer, Virginia M Sanders, Kathryn J Jones
BACKGROUND: When nerve transection is performed on adult rodents, a substantial population of neurons survives short-term disconnection from target, and the immune system supports this neuronal survival, however long-term survival remains unknown. Understanding the effects of permanent axotomy on cell body survival is important as target disconnection is the first pathological occurrence in fatal motoneuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA)...
March 25, 2018: Restorative Neurology and Neuroscience
https://www.readbyqxmd.com/read/29608575/ozanimod-rpc1063-a-selective-s1pr1-and-s1pr5-modulator-reduces-chronic-inflammation-and-alleviates-kidney-pathology-in-murine-systemic-lupus-erythematosus
#2
Kristen R Taylor Meadows, Marcos W Steinberg, Bryan Clemons, Matthew E Stokes, Gregory J Opiteck, Robert Peach, Fiona L Scott
Ozanimod (RPC1063) is a specific and potent small molecule modulator of the sphingosine 1-phosphate receptor 1 (S1PR1) and receptor 5 (S1PR5), which has shown therapeutic benefit in clinical trials of relapsing multiple sclerosis and ulcerative colitis. Ozanimod and its active metabolite, RP-101075, exhibit a similar specificity profile at the S1P receptor family in vitro and pharmacodynamic profile in vivo. The NZBWF1 mouse model was used in therapeutic dosing mode to assess the potential benefit of ozanimod and RP-101075 in an established animal model of systemic lupus erythematosus...
2018: PloS One
https://www.readbyqxmd.com/read/29606295/the-roles-of-macrophages-and-microglia-in-multiple-sclerosis-and-experimental-autoimmune-encephalomyelitis
#3
REVIEW
Fengna Chu, Mingchao Shi, Chao Zheng, Donghui Shen, Jie Zhu, Xiangyu Zheng, Li Cui
Multiple sclerosis (MS) is an autoimmune and neurodegenerative disorder characterized by chronic inflammation, demyelination, as well as axonal and neuronal loss in the central nervous system (CNS). Macrophages and microglia are important components of the innate immune system. They participate in the primary response to microorganisms and play a role in inflammatory responses, homeostasis, and tissue regeneration. In the initial phase of MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS, macrophages from peripheral tissues infiltrate into the CNS and, together with residential microglia, contribute to the pathogenesis of MS...
May 15, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29604346/dithiolethione-acdt-suppresses-neuroinflammation-and-ameliorates-disease-severity-in-experimental-autoimmune-encephalomyelitis
#4
Ping-Chang Kuo, Dennis A Brown, Barbara A Scofield, Hallel C Paraiso, Pei-Yu Wang, I-Chen Yu, Jui-Hung Yen
Multiple sclerosis (MS) is an autoimmune disorder characterized by the central nervous system (CNS) infiltration of myelin-specific pathogenic T cells followed by brain inflammation in association with demyelination. Similarly, experimental autoimmune encephalomyelitis (EAE), the animal model of MS, also exhibits increased CNS infiltration of pathogenic T cells, including Th1 and Th17, leading to detrimental effects of neuroinflammation and demyelination. We previously reported that 3H-1,2-dithiole-3-thione (D3T), the structurally-simplest of the sulfur-containing dithiolethiones, exerted a promising therapeutic effect in EAE...
March 28, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29577640/a-kv1-3-channel-specific-blocker-alleviates-neurological-impairment-through-inhibiting-t-cell-activation-in-experimental-autoimmune-encephalomyelitis
#5
Xiao-Lu Yuan, Yi-Peng Zhao, Jie Huang, Jun-Chen Liu, Wen-Qian Mao, Jun Yin, Bi-Wen Peng, Wan-Hong Liu, Song Han, Xiao-Hua He
AIM: Multiple sclerosis (MS) is a neurological autoimmune disorder characterized by mistaken attacks of inflammatory cells against the central nervous system (CNS), resulting in demyelination and axonal damage. Kv1.3 channel blockers can inhibit T-cell activation and have been designed for MS therapy. However, little is known about the effects of Kv1.3 blockers on protecting myelin sheaths/axons in MS. This study aimed at investigating the neuroprotection efficacy of a selective Kv1.3 channel blocker ImKTx88 (ImK) in MS animal model...
March 25, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29557516/olfactory-dysfunction-in-autoimmune-central-nervous-system-neuroinflammation
#6
Jeongtae Kim, Yuna Choi, Meejung Ahn, Kyungsook Jung, Taekyun Shin
Olfactory dysfunction is an early sign of neuroinflammation of the central nervous system (CNS). Microgliosis and astrogliosis are representative pathological changes that develop during neuroinflammation of CNS tissues. Autoimmune CNS inflammation, including human multiple sclerosis, is an occasional cause of olfactory disorders. We evaluated whether gliosis and olfactory dysfunction developed in animals with experimental autoimmune encephalomyelitis (EAE), a model of human multiple sclerosis. Neuroinflammatory lesions characterized by infiltration of inflammatory cells and microglial cell activation were occasionally found in the olfactory bulbs of EAE-affected rats...
March 20, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29548931/chronobiological-regulation-of-psychosocial-and-physiological-outcomes-in-multiple-sclerosis
#7
REVIEW
Elisea De Somma, Rajiv W Jain, Kelvin W C Poon, Kaitlyn A Tresidder, Julia P Segal, Nader Ghasemlou
There is mounting scientific evidence showing the importance of innate biological rhythms on disease onset and progression. Perhaps the most important of these is the circadian rhythm, a cycle of oscillations lasting approximately 24 hours. Recent work has shown that circadian rhythms are intrinsically linked to the immune system in a bidirectional fashion, and disruption of these cycles can contribute to changes in pathology and quality of life (including fatigue, mood, and disability). This is particularly true in diseases of the nervous and immune systems...
March 13, 2018: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29547745/stem-cell-derived-phenotypic-human-neuromuscular-junction-model-for-dose-response-evaluation-of-therapeutics
#8
Navaneetha Santhanam, Lee Kumanchik, Xiufang Guo, Frank Sommerhage, Yunqing Cai, Max Jackson, Candace Martin, George Saad, Christopher W McAleer, Ying Wang, Andrea Lavado, Christopher J Long, James J Hickman
There are currently no functional neuromuscular junction (hNMJ) systems composed of human cells that could be used for drug evaluations or toxicity testing in vitro. These systems are needed to evaluate NMJs for diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy or other neurodegenerative diseases or injury states. There are certainly no model systems, animal or human, that allows for isolated treatment of motoneurons or muscle capable of generating dose response curves to evaluate pharmacological activity of these highly specialized functional units...
February 27, 2018: Biomaterials
https://www.readbyqxmd.com/read/29545809/the-autoimmune-skin-disease-bullous-pemphigoid-the-role-of-mast-cells-in-autoantibody-induced-tissue-injury
#9
REVIEW
Hui Fang, Yang Zhang, Ning Li, Gang Wang, Zhi Liu
Bullous pemphigoid (BP) is an autoimmune and inflammatory skin disease associated with subepidermal blistering and autoantibodies directed against the hemidesmosomal components BP180 and BP230. Animal models of BP were developed by passively transferring anti-BP180 IgG into mice, which recapitulates the key features of human BP. By using these in vivo model systems, key cellular and molecular events leading to the BP disease phenotype are identified, including binding of pathogenic IgG to its target, complement activation of the classical pathway, mast cell degranulation, and infiltration and activation of neutrophils...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29536745/astaxanthin-effectiveness-in-preventing-multiple-sclerosis-in-animal-model
#10
S Bidaran, A R Ahmadi, P Yaghmaei, M H Sanati, A Ebrahim-Habibi
OBJECTIVE: The aim of the present study was to reveal the effect of therapeutic and prophylactic potential of astaxanthin in experimental autoimmune encephalomyelitis (EAE) as an acceptable model for the study of multiple sclerosis (MS). BACKGROUND: Astaxanthin has powerful antioxidant activities as well as several essential biological functions while multiple sclerosis prevention is highly regarded by researchers. METHODS: The astaxanthin potential in prevention of multiple sclerosis was examined in the chronic model of experimental autoimmune encephalomyelitis (EAE) by using female C57BL/6 mice induced with oligodendrocyte glycoprotein (MOG)...
2018: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/29534847/neuregulin1-modulation-of-experimental-autoimmune-encephalomyelitis-eae
#11
Elise Allender, Harvinderjeet Deol, Sarah Schram, Kathleen J Maheras, Alexander Gow, Eleanor H Simpson, Fei Song
Neuregulin1 (NRG1) is a differentiation factor that regulates glial development, survival, synaptogenesis, axoglial interactions, and microglial activation. We previously reported that a targeted NRG1 antagonist (HBD-S-H4) given intrathecally, reduces inflammatory microglial activation in a spinal cord pain model and a neurodegenerative disease mouse model in vivo, suggesting that it may have effects in neuroninflammatory and neuronal disorders. We hypothesized that expression of HBD-S-H4 in the central nervous system (CNS) could reduce disease severity in experimental autoimmune encephalomyelitis (EAE), a widely used animal model for multiple sclerosis (MS)...
March 10, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29526318/a-comparative-study-of-melatonin-and-immunomodulatory-therapy-with-interferon-beta-and-glatiramer-acetate-in-a-mouse-model-of-multiple-sclerosis
#12
E J Ramos González, L J Ramirez Jirano, D Z García Martínez, G G Ortiz, L F Jave Suárez, C A Leal Cortes, O K Bitzer Quintero
INTRODUCTION: Multiple sclerosis (MS) is a chronic, demyelinating, autoimmune disease of the central nervous system causing neuroinflammation. Experimental autoimmune encephalitis (EAE) is a model of the disease. MS is classically treated with interferon beta (IFN-β) and glatiramer acetate (GA). Melatonin (MLT) has been reported to modulate immune system responses. The aim of the present study is to analyse the effects of MLT administration in comparison with the first-line treatments for MS (IFN-β and GA)...
March 8, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/29524628/assessment-of-metal-concentrations-in-the-sod1-g93a-mouse-model-of-amyotrophic-lateral-sclerosis-and-its-potential-role-in-muscular-denervation-with-particular-focus-on-muscle-tissue
#13
T Gabriel Enge, Heath Ecroyd, Dianne F Jolley, Justin J Yerbury, Bernadett Kalmar, Anthony Dosseto
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is among the most common of the motor neuron diseases, and arguably the most devastating. During the course of this fatal neurodegenerative disorder, motor neurons undergo progressive degeneration. The currently best-understood animal models of ALS are based on the over-expression of mutant isoforms of Cu/Zn superoxide dismutase 1 (SOD1); these indicate that there is a perturbation in metal homeostasis with disease progression. Copper metabolism in particular is affected in the central nervous system (CNS) and muscle tissue...
March 7, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29518786/analysis-of-long-noncoding-rna-and-mrna-expression-profiles-in-il-9-activated-astrocytes-and-eae-mice
#14
Xiaomei Liu, Qing Zhang, Weixiao Wang, Dongjiao Zuo, Jing Wang, Feng Zhou, Liping Niu, Xiangyang Li, Suping Qin, Yanbo Kou, Fanyun Kong, Wei Pan, Yugang Wang, Dianshuai Gao, Hong Sun, Jessica M Meves, Kuiyang Zheng, Renxian Tang
BACKGROUND/AIMS: Multiple sclerosis (MS) is an autoimmune disease in the central nervous system associated with demyelination and axonal injury. Astrocyte activation is involved in the pathogenesis of MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. This study was designed to find potential lncRNAs in EAE mice and activated astrocytes. METHODS: we performed microarray analysis of lncRNAs from the brain tissues of EAE mice and primary mouse astrocytes treated with IL-9(50 ng/ml)...
March 2, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29518037/the-modulatory-roles-of-n-glycans-in-t-cell-mediated-autoimmune-diseases
#15
REVIEW
Ming-Wei Chien, Shin-Huei Fu, Chao-Yuan Hsu, Yu-Wen Liu, Huey-Kang Sytwu
Glycosylation is a ubiquitous posttranslational modification of proteins that occurs in the endoplasmic reticulum/Golgi. N -glycans and mucin-type O -glycans are achieved via a series of glycohydrolase- and glycosyltransferase-mediated reactions. Glycosylation modulates immune responses by regulating thymocyte development and T helper cell differentiation. Autoimmune diseases result from an abnormal immune response by self-antigens and subsequently lead to the destruction of the target tissues. The modification of N -glycans has been studied in several animal models of T-cell-mediated autoimmune diseases...
March 8, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29515033/calnexin-is-necessary-for-t-cell-transmigration-into-the-central-nervous-system
#16
Joanna Jung, Paul Eggleton, Alison Robinson, Jessica Wang, Nick Gutowski, Janet Holley, Jia Newcombe, Elzbieta Dudek, Amber M Paul, Douglas Zochodne, Allison Kraus, Christopher Power, Luis B Agellon, Marek Michalak
In multiple sclerosis (MS), a demyelinating inflammatory disease of the CNS, and its animal model (experimental autoimmune encephalomyelitis; EAE), circulating immune cells gain access to the CNS across the blood-brain barrier to cause inflammation, myelin destruction, and neuronal damage. Here, we discovered that calnexin, an ER chaperone, is highly abundant in human brain endothelial cells of MS patients. Conversely, mice lacking calnexin exhibited resistance to EAE induction, no evidence of immune cell infiltration into the CNS, and no induction of inflammation markers within the CNS...
March 8, 2018: JCI Insight
https://www.readbyqxmd.com/read/29507931/association-of-regulatory-t-cell-expansion-with-progression-of-amyotrophic-lateral-sclerosis-a-study-of-humans-and-a-transgenic-mouse-model
#17
Rebecca K Sheean, Fiona C McKay, Erika Cretney, Christopher R Bye, Nirma D Perera, Doris Tomas, Richard A Weston, Karlene J Scheller, Elvan Djouma, Parvathi Menon, Stephen D Schibeci, Najwa Marmash, Justin J Yerbury, Stephen L Nutt, David R Booth, Graeme J Stewart, Mathew C Kiernan, Steve Vucic, Bradley J Turner
Importance: Neuroinflammation appears to be a key modulator of disease progression in amyotrophic lateral sclerosis (ALS) and thereby a promising therapeutic target. The CD4+Foxp3+ regulatory T-cells (Tregs) infiltrating into the central nervous system suppress neuroinflammation and promote the activation of neuroprotective microglia in mouse models of ALS. To our knowledge, the therapeutic association of host Treg expansion with ALS progression has not been studied in vivo. Objective: To assess the role of Tregs in regulating the pathophysiology of ALS in humans and the therapeutic outcome of increasing Treg activity in a mouse model of the disease...
March 5, 2018: JAMA Neurology
https://www.readbyqxmd.com/read/29492193/preclinical-evaluation-of-the-pi3k-akt-mtor-pathway-in-animal-models-of-multiple-sclerosis
#18
Santa Mammana, Placido Bramanti, Emanuela Mazzon, Eugenio Cavalli, Maria Sofia Basile, Paolo Fagone, Maria Cristina Petralia, James Andrew McCubrey, Ferdinando Nicoletti, Katia Mangano
The PI3K/AKT/mTOR pathway is an intracellular signalling pathway that regulates cell activation. proliferation, metabolism and apoptosis. Increasing body of data suggests that alterations in the PI3K/AKT/mTOR pathway may result in an enhanced susceptibility to autoimmunity. Multiple Sclerosis (MS) is one of the most common chronic inflammatory diseases of the central nervous system leading to demyelination and neurodegeneration. In the current study, we have firstly evaluated in silico the involvement of the mTOR network on the generation and progression of MS and on oligodendrocyte function, making use of currently available whole-genome transcriptomic data...
February 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29475340/label-free-photoacoustic-imaging-guided-sclerotherapy-for-vascular-malformations-a-feasibility-study
#19
Jiawei Sun, Quan Zhou, Sihua Yang
We used high-resolution photoacoustic imaging (PAI) to guide sclerotherapy of vascular malformations in an in vivo animal model. A focus-adjustable PAI system was developed. It can adapt to the imaging needs of different depths by adjusting the focus. Blood samples drawn before and after sclerosis were examined with PAI, which could distinguish whether or not the blood had been exposed to a sclerosing agent. Superficial and deep vessels in the animal model were examined in vivo to prove the feasibility of guiding sclerotherapy...
February 19, 2018: Optics Express
https://www.readbyqxmd.com/read/29465302/merits-and-complexities-of-modeling-multiple-sclerosis-in-non-human-primates-implications-for-drug-discovery
#20
Bert A 't Hart, Jon D Laman, Yolanda S Kap
The translation of scientific discoveries made in animal models into effective treatments for patients often fails, indicating that currently used disease models in preclinical research are insufficiently predictive for clinical success. An often-used model in the preclinical research of autoimmune neurological diseases, multiple sclerosis in particular, is experimental autoimmune encephalomyelitis (EAE). Most EAE models are based on genetically susceptible inbred/SPF mouse strains used at adolescent age (10-12 weeks), which lack exposure to genetic and microbial factors which shape the human immune system...
February 21, 2018: Expert Opinion on Drug Discovery
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