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Systemic sclerosis animal model

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https://www.readbyqxmd.com/read/28238951/oral-administration-of-the-nitroxide-radical-tempol-exhibits-immunomodulatory-and-therapeutic-properties-in-multiple-sclerosis-models
#1
Sarah Neil, Jaebong Huh, Victoria Baronas, Xinhui Li, Henry F McFarland, Murali Cherukuri, James B Mitchell, Jacqueline A Quandt
Therapies with both immunomodulatory and neuroprotective properties are thought to have the greatest promise in reducing the severity and progression of multiple sclerosis (MS). Several reactive oxygen (ROS) and reactive nitrogen species (RNS) are implicated in inflammatory-mediated damage to the central nervous system (CNS) in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) is a stable nitroxide radical with potent antioxidant activity...
February 23, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28236206/glutamate-t-cells-and-multiple-sclerosis
#2
REVIEW
Mia Levite
Glutamate is the major excitatory neurotransmitter in the nervous system, where it induces multiple beneficial and essential effects. Yet, excess glutamate, evident in a kaleidoscope of acute and chronic pathologies, is absolutely catastrophic, since it induces excitotoxicity and massive loss of brain function. Both the beneficial and the detrimental effects of glutamate are mediated by a large family of glutamate receptors (GluRs): the ionotropic glutamate receptors (iGluRs) and the metabotropic glutamate receptors (mGluRs), expressed by most/all cells of the nervous system, and also by many non-neural cells in various peripheral organs and tissues...
February 24, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28235673/laquinimod-enhances-central-nervous-system-barrier-functions
#3
Fred Lühder, Hania Kebir, Francesca Odoardi, Tanja Litke, Maike Sonneck, Jorge Ivan Alvarez, Jan Winchenbach, Nadine Eckert, Liat Hayardeny, Ella Sorani, Dmitri Lodygin, Alexander Flügel, Alexandre Prat
Laquinimod is currently being tested as a therapeutic drug in multiple sclerosis. However, its exact mechanism of action is still under investigation. Tracking of fluorescently-tagged encephalitogenic T cells during experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, revealed that laquinimod significantly reduces the invasion of pathogenic effector T cells into the CNS tissue. T-cell activation, differentiation and amplification within secondary lymphoid organs after immunization with myelin antigen, their migratory capacity and re-activation within the nervous tissue were either only mildly affected or remained unchanged...
February 21, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28231624/targets-and-mechanisms-in-prevention-of-parkinson-s-disease-through-immunomodulatory-treatments
#4
REVIEW
Marianne von Euler Chelpin, Thomas Vorup-Jensen
Parkinson's Disease (PD) is the second most common neurodegenerative disease in the world, however, there is no cure for it. Current treatments only relieve some of the symptoms, without ceasing the disease, and lose efficacy with prolonged treatment. Considerable evidence shows that persistent inflammatory responses, involving T cell infiltration and glial cell activation, are common characteristics of human patients and play a crucial role in the degeneration of dopaminergic neurons. Therefore, it is important to develop therapeutic strategies that can impede or halt the disease through the modulation of the peripheral immune system by aiming at controlling the existing neuroinflammation...
February 23, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28223983/b-cell-homeostasis-and-functional-properties-are-altered-in-an-hypochlorous-acid-induced-murine-model-of-systemic-sclerosis
#5
Sébastien Sanges, Manel Jendoubi, Niloufar Kavian, Carine Hauspie, Silvia Speca, Jean-Charles Crave, Thomas Guerrier, Guillaume Lefèvre, Vincent Sobanski, Ariel Savina, Eric Hachulla, Pierre-Yves Hatron, Myriam Labalette, Frédéric Batteux, Sylvain Dubucquoi, David Launay
INTRODUCTION: During systemic sclerosis (SSc), peripheral B cells display alterations in subset homeostasis and functional properties and are a promising therapeutic target. However, there is only few data regarding whether these anomalies are accurately reproduced in animal models of SSc. OBJECTIVE: In this work, we assessed the B cell homeostasis modifications in an experimental model of SSc [hypochlorous acid (HOCl)-induced mouse], both at a phenotypic and functional level, during the course of the disease...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28205575/cu-ii-atsm-improves-the-neurological-phenotype-and-survival-of-sod1-g93a-mice-and-selectively-increases-enzymatically-active-sod1-in-the-spinal-cord
#6
James B Hilton, Stephen W Mercer, Nastasia K H Lim, Noel G Faux, Gojko Buncic, Joseph S Beckman, Blaine R Roberts, Paul S Donnelly, Anthony R White, Peter J Crouch
Ubiquitous expression of mutant Cu/Zn-superoxide dismutase (SOD1) selectively affects motor neurons in the central nervous system (CNS), causing the adult-onset degenerative disease amyotrophic lateral sclerosis (ALS). The CNS-specific impact of ubiquitous mutant SOD1 expression is recapitulated in transgenic mouse models of the disease. Here we present outcomes for the metallo-complex Cu(II)(atsm) tested for therapeutic efficacy in mice expressing SOD1(G93A) on a mixed genetic background. Oral administration of Cu(II)(atsm) delayed the onset of neurological symptoms, improved locomotive capacity and extended overall survival...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202908/silencing-c-rel-in-macrophages-dampens-th1-and-th17-immune-responses-and-alleviates-experimental-autoimmune-encephalomyelitis-in-mice
#7
Hongling Zhang, Jiacheng Bi, Huqiang Yi, Tingting Fan, Qingguo Ruan, Lintao Cai, Youhai H Chen, Xiaochun Wan
Autoimmune Th1 and Th17 responses are critical for the development of central nervous system (CNS) pathology in experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. Although macrophages play important roles in the development of Th1 and Th17 responses, whether modulating macrophage gene transcription can diminish Th1- and Th17 cell-induced CNS pathology is unclear. In this study, we successfully silenced the expression of the transcription factor c-Rel in macrophages of mice with EAE (including those infiltrating the CNS) using chemically modified c-Rel-specific siRNAs delivered by nanoparticles...
February 16, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28197175/can-cannabinoids-be-a-potential-therapeutic-tool-in-amyotrophic-lateral-sclerosis
#8
REVIEW
Sabrina Giacoppo, Emanuela Mazzon
Amyotrophic lateral sclerosis (ALS) is the most common degenerative disease of the motor neuron system. Over the last years, a growing interest was aimed to discovery new innovative and safer therapeutic approaches in the ALS treatment. In this context, the bioactive compounds of Cannabis sativa have shown antioxidant, anti-inflammatory and neuroprotective effects in preclinical models of central nervous system disease. However, most of the studies proving the ability of cannabinoids in delay disease progression and prolong survival in ALS were performed in animal model, whereas the few clinical trials that investigated cannabinoids-based medicines were focused only on the alleviation of ALS-related symptoms, not on the control of disease progression...
December 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28195514/blood-brain-barrier-on-a-chip-microphysiological-systems-that-capture-the-complexity-of-the-blood-central-nervous-system-interface
#9
Duc Tt Phan, R Hugh F Bender, Jillian W Andrejecsk, Agua Sobrino, Stephanie J Hachey, Steven C George, Christopher Cw Hughes
The blood-brain barrier is a dynamic and highly organized structure that strictly regulates the molecules allowed to cross the brain vasculature into the central nervous system. The blood-brain barrier pathology has been associated with a number of central nervous system diseases, including vascular malformations, stroke/vascular dementia, Alzheimer's disease, multiple sclerosis, and various neurological tumors including glioblastoma multiforme. There is a compelling need for representative models of this critical interface...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28186117/amelioration-of-experimental-autoimmune-encephalomyelitis-through-transplantation-of-placental-derived-mesenchymal-stem-cells
#10
Hong Jiang, Yuanyuan Zhang, Kewei Tian, Beibei Wang, Shu Han
Placental derived mesenchymal stem cells (PMSCs) have been suggested as a possible source of cells to treat multiple sclerosis (MS) due to their immunomodulatory functions, lack of ethical concerns, and potential to differentiate into neurons and oligodendrocytes. To investigate whether PMSCs share similar characteristics with embryonic mesenchymal stem cells (EMSCs), and if transplanted PMSCs have the ability to integrate and replace degenerated neural cells, we transplanted rat PMSCs and EMSCs into the central nervous system (CNS) of Lewis rats with experimental autoimmune encephalomyelitis (EAE), an animal model of MS...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28181561/peripheral-sensory-neuron-injury-contributes-to-neuropathic-pain-in-experimental-autoimmune-encephalomyelitis
#11
I-Ching Wang, Chen-Yen Chung, Fang Liao, Chih-Cheng Chen, Cheng-Han Lee
Multiple sclerosis (MS)-induced neuropathic pain deteriorates quality of life in patients but is often refractory to treatment. In experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, animals develop neuropathy and inflammation-induced tissue acidosis, which suggests the involvement of acid-sensing ion channels (ASICs). Also, peripheral neuropathy is reported in MS patients. However, the involvement of the peripheral nervous system (PNS) in MS neuropathic pain remains elusive. This study investigated the contribution of ASICs and peripheral neuropathy in MS-induced neuropathic pain...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28165507/paeoniflorin-ameliorates-experimental-autoimmune-encephalomyelitis-via-inhibition-of-dendritic-cell-function-and-th17-cell-differentiation
#12
Han Zhang, Yuanyuan Qi, Yuanyang Yuan, Li Cai, Haiyan Xu, Lili Zhang, Bing Su, Hong Nie
Paeoniflorin (PF) is a monoterpene glycoside and exhibits multiple effects, including anti-inflammation and immunoregulation. To date, the effect of PF on multiple sclerosis (MS) has not been investigated. In this study, we investigated the effect of PF in experimental autoimmune encephalomyelitis (EAE), an animal model for MS. After administered with PF, the onset and clinical symptoms of EAE mice were significantly ameliorated, and the number of Th17 cells infiltrated in central nervous system (CNS) and spleen was also dramatically decreased...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28161558/neutrophil-perversion-in-demyelinating-autoimmune-diseases-mechanisms-to-medicine
#13
REVIEW
Courtney S Casserly, Julia C Nantes, Ryder F Whittaker Hawkins, Luc Vallières
Neutrophils are essential to a healthy life, yet pose a threat if improperly controlled. Neutrophil perversion is well documented in a variety of inflammatory disorders (e.g. arthritis, lupus, psoriasis), but is only beginning to be demystified in autoimmune demyelination, the most common cause of neurological disability in young adults. Using the animal model experimental autoimmune encephalomyelitis (EAE), several molecules that help neutrophils invade the central nervous system (CNS) have been identified...
February 2, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28157273/a-novel-animal-model-of-acquired-human-temporal-lobe-epilepsy-based-on-the-simultaneous-administration-of-kainic-acid-and-lorazepam
#14
Friederike Kienzler-Norwood, Lara Costard, Chinmaya Sadangi, Philipp Müller, Valentin Neubert, Sebastian Bauer, Felix Rosenow, Braxton A Norwood
OBJECTIVE: Kainic acid (KA) is a potent glutamate analog that is used to induce neurodegeneration and model temporal lobe epilepsy (TLE) in rodents. KA reliably induces severe, prolonged seizures, that is, convulsive status epilepticus (cSE), which is typically fatal without pharmacologic intervention. Although the use of KA to model human epilepsy has proven unquestionably valuable for >30 years, significant variability and mortality continue to confound results. These issues are probably the consequence of cSE, an all-or-nothing response that is inherently capricious and uncontrollable...
February 2017: Epilepsia
https://www.readbyqxmd.com/read/28130201/ucp2-up-regulation-within-the-course-of-autoimmune-encephalomyelitis-correlates-with-t-lymphocyte-activation
#15
Alina Smorodchenko, Stephanie Schneider, Anne Rupprecht, Karoline Hilse, Soleman Sasgary, Ute Zeitz, Reinhold G Erben, Elena E Pohl
Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disorder of the central nervous system (CNS) associated with severe neurological disability. Reactive oxygen species (ROS) and mitochondrial dysfunction play a pivotal role in the pathogenesis of this disease. Several members of the mitochondrial uncoupling protein subfamily (UCP2-UCP5) were suggested to regulate ROS by diminishing the mitochondrial membrane potential and constitute therefore a promising pharmacological target for MS. To evaluate the role of different uncoupling proteins in neuroinflammation, we have investigated their expression patterns in murine brain and spinal cord (SC) during different stages of experimental autoimmune encephalomyelitis (EAE), an animal model for MS...
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28124770/the-effect-of-stereotactic-injections-on-demyelination-and-remyelination-a-study-in-the-cuprizone-model
#16
Laura Salinas Tejedor, Tanja Wostradowski, Stefan Gingele, Thomas Skripuletz, Viktoria Gudi, Martin Stangel
Remyelination is the natural repair mechanism in demyelinating disorders of the central nervous system (CNS) such as multiple sclerosis. Several animal models have been used to study demyelination and remyelination. Among toxic animal models, oral administration of the toxin cuprizone leads to white and gray matter demyelination. In contrast, focal demyelination models include the stereotactic application of a toxin such as lysolecithin or ethidium bromide. The injection procedure generates a local disruption of the blood-brain barrier (BBB) and might thus trigger a local inflammatory reaction and consequently may influence demyelination and remyelination...
January 26, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28112256/fsd-c10-a-fasudil-derivative-promotes-neuroregeneration-through-indirect-and-direct-mechanisms
#17
Yan-Hua Li, Chong Xie, Yuan Zhang, Xing Li, Hai-Fei Zhang, Qing Wang, Zhi Chai, Bao-Guo Xiao, Rodolfo Thome, Guang-Xian Zhang, Cun-Gen Ma
FSD-C10, a Fasudil derivative, was shown to reduce severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through the modulation of the immune response and induction of neuroprotective molecules in the central nervous system (CNS). However, whether FSD-C10 can promote neuroregeneration remains unknown. In this study, we further analyzed the effect of FSD-C10 on neuroprotection and remyelination. FSD-C10-treated mice showed a longer, thicker and more intense MAP2 and synaptophysin positive signal in the CNS, with significantly fewer CD4(+) T cells, macrophages and microglia...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28095319/autophagy-and-autoimmunity
#18
REVIEW
Dennis J Wu, Iannis E Adamopoulos
Autophagy is a highly conserved protein degradation pathway from yeasts to humans that is essential for removing protein aggregates and misfolded proteins in healthy cells. Recently, autophagy-related genes polymorphisms have been implicated in several autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, psoriasis, and multiple sclerosis. Numerous studies reveal autophagy and autophagy-related proteins also participate in immune regulation. Conditional deletions of autophagy-related proteins in mice have rendered protection from experimental autoimmune encephalomyelitis, and TNF-mediated joint destruction in animal models of multiple sclerosis and experimental arthritis respectively...
January 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28067393/longitudinal-assessment-of-metal-concentrations-and-copper-isotope-ratios-in-the-g93a-sod1-mouse-model-of-amyotrophic-lateral-sclerosis
#19
T Gabriel Enge, Heath Ecroyd, Dianne F Jolley, Justin J Yerbury, Anthony Dosseto
Amyotrophic lateral sclerosis (ALS) is a motor neuron disease, which involves progressive motor neuron degeneration in the central nervous system (CNS). The G93A SOD1 mouse model simulates one of the most common causes of familial ALS through the overexpression of a mutated form of the human gene encoding copper/zinc superoxide dismutase (SOD1). Transition metals, particularly Cu and Zn, have been shown to behave abnormally in the disease context and have been hypothesized to contribute to and potentially trigger the disease...
January 9, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28063173/identification-of-highly-connected-hub-genes-in-the-protective-response-program-of-human-macrophages-and-microglia-activated-by-alpha-b-crystallin
#20
Inge R Holtman, Malika Bsibsi, Wouter H Gerritsen, Hendrikus W G M Boddeke, Bart J L Eggen, Paul van der Valk, Markus Kipp, Johannes M van Noort, Sandra Amor
The glial stress protein alpha B-crystallin (HSPB5) is an endogenous agonist for Toll-like receptor 2 in CD14(+) cells. Following systemic administration, HSPB5 acts as a potent inhibitor of neuroinflammation in animal models and reduces lesion development in multiple sclerosis patients. Here, we show that systemically administered HSPB5 rapidly crosses the blood-brain barrier, implicating microglia as additional targets for HSPB5 along with peripheral monocytes and macrophages. To compare key players in the HSPB5-induced protective response of human macrophages and microglia, we applied weighted gene co-expression network analysis on transcript expression data obtained 1 and 4 h after activation...
January 7, 2017: Glia
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