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Systemic sclerosis animal model

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https://www.readbyqxmd.com/read/29226387/systemic-sclerosis
#1
REVIEW
Yoshihide Asano
Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by vasculopathy and tissue fibrosis of the skin and various internal organs. A series of genetic and epidemiological studies have demonstrated that SSc onset is determined by the accumulation of predisposing factors related to environmental influences, while genetic factors affect the susceptibility to and the severity of this disease. This notion has been confirmed by recent advance in animal models. The initial trigger of SSc is believed to be autoimmune attacks to endothelial cells, which occur in individuals with the genetic susceptibility to autoimmune diseases and/or the cumulative exposure to certain SSc-related environmental influences...
December 10, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/29222794/active-induction-of-experimental-autoimmune-encephalomyelitis-in-c57bl-6-mice
#2
Gabriella Contarini, Pietro Giusti, Stephen D Skaper
The protocol in this chapter presents a method to actively induce experimental autoimmune encephalomyelitis (EAE), one of the most widely used animal models to study efficacy of potential drugs for treatment of multiple sclerosis. Multiple sclerosis is an inflammatory, demyelinating disease of the central nervous system and the most common cause of chronic neurological impairment in young people. In this model EAE is induced in female C57BL/6 mice by immunization with an emulsion of myelin oligodendrocyte glycoprotein (fragment 35-55) in complete Freund's adjuvant, followed by administration of pertussis toxin in phosphate-buffered saline...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29208474/caenorhabditis-elegans-as-a-model-system-for-target-identification-and-drug-screening-against-neurodegenerative-diseases
#3
REVIEW
Liang Ma, Yudan Zhao, Yuchen Chen, Biao Cheng, Anlin Peng, Kun Huang
Over the past decades, C. elegans has been widely used as a model system because of its small size, transparent body, short generation time and lifespan (~3 days and 3 weeks, respectively), completely sequenced genome and tractability to genetic manipulation. Protein misfolding and aggregation are key pathological features in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Animal models, including Caenorhabditis elegans (C...
December 2, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29203425/tgf%C3%AE-1-transduction-enhances-immunomodulatory-capacity-of-neural-stem-cells-in-experimental-autoimmune-encephalomyelitis
#4
Chong Xie, Xing Li, Xiajun Zhou, Zezhi Li, Yuan Zhang, Li Zhao, Yong Hao, Guang-Xian Zhang, Yangtai Guan
Bone marrow-derived neural stem cells (BM-NSCs) have therapeutic effect on EAE, an animal model of multiple sclerosis. However, the beneficial effect is suboptimal due to the limited immunomodulatory capacity of these cells. In this study, we engineered BM-NSCs with inducible TGFβ1, a potent immunosuppressive cytokine, to enhance their anti-inflammatory capacity. We found that i.v. injected TGFβ1-BM-NSCs more effectively suppressed clinical severity, inflammation and demyelination of the central nervous system of EAE mice...
December 1, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29191793/combined-therapies-to-treat-complex-diseases-the-role-of-the-gut-microbiota-in-multiple-sclerosis
#5
REVIEW
Laura Calvo-Barreiro, Herena Eixarch, Xavier Montalban, Carmen Espejo
The commensal microbiota has emerged as an environmental risk factor for multiple sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE) models have shown that the commensal microbiota is an essential player in triggering autoimmune demyelination. Likewise, the commensal microbiota modulates the host immune system, alters the integrity and function of biological barriers and has a direct effect on several types of central nervous system (CNS)-resident cells. Moreover, a characteristic gut dysbiosis has been recognized as a consistent feature during the clinical course of MS, and the MS-related microbiota is gradually being elucidated...
November 27, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29187524/dtbc1d7-regulates-systemic-growth-independently-of-tsc-through-insulin-signaling
#6
Suxia Ren, Zengyi Huang, Yuqiang Jiang, Tao Wang
The insulin signaling pathway plays key roles in systemic growth. TBC1D7 has recently been identified as the third subunit of the tuberous sclerosis complex (TSC), a negative regulator of cell growth. Here, we used Drosophila as a model system to dissect the physiological function of TBC1D7 in vivo. In mutants lacking TBC1D7, cell and organ growth were promoted, and TBC1D7 limited cell growth in a cell-nonautonomous and TSC-independent manner. TBC1D7 is specifically expressed in insulin-producing cells in the fly brain and regulated biosynthesis and release of insulin-like peptide 2, leading to systemic growth...
November 29, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29169241/gut-reactions-how-the-blood-brain-barrier-connects-the-microbiome-and-the-brain
#7
Aric F Logsdon, Michelle A Erickson, Elizabeth M Rhea, Therese S Salameh, William A Banks
A growing body of evidence indicates that the microbiome interacts with the central nervous system (CNS) and can regulate many of its functions. One mechanism for this interaction is at the level of the blood-brain barriers (BBBs). In this minireview, we examine the several ways the microbiome is known to interact with the CNS barriers. Bacteria can directly release factors into the systemic circulation or can translocate into blood. Once in the blood, the microbiome and its factors can alter peripheral immune cells to promote interactions with the BBB and ultimately with other elements of the neurovascular unit...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29153606/pegylated-interferon-beta-in-the-treatment-of-the-theiler-s-murine-encephalomyelitis-virus-mouse-model-of-multiple-sclerosis
#8
Francesca Gilli, Darlene B Royce, Krista D DiSano, Andrew R Pachner
We evaluated the effects of pegylated-interferonβ-1a (pegIFNβ) therapy on intrathecal antibody responses, disability progression, and viral load in the CNS in mice infected with the Theiler's virus (TMEV), an animal model of progressive disability in Multiple Sclerosis (MS). The lack of a direct antiviral activity in the CNS, the absence of any effect upon the intrathecal immune response, and the failure to treat disease progression, indicate that the immunomodulatory effects of pegIFNβ-1a likely occur in the systemic circulation rather than within the CNS...
December 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29150766/spinobot-an-mri-guided-needle-positioning-system-for-spinal-cellular-therapeutics
#9
Alexander Squires, John N Oshinski, Nicholas M Boulis, Zion Tsz Ho Tse
The neurodegenerative disease amyotrophic lateral sclerosis (ALS) results in the death of motor neurons in voluntary muscles. There are no cures for ALS and few available treatments. In studies with small animal models, injection of cellular therapeutics into the anterior horn of the spinal cord has been shown to inhibit the progression of ALS. It was hypothesized that spinal injection could be made faster and less invasive with the aid of a robot. The robotic system presented-SpinoBot-uses MRI guidance to position a needle for percutaneous injection into the spinal cord...
November 17, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/29149058/neurotrophic-and-neuroregenerative-effects-of-gh-igf1
#10
Vittorio Emanuele Bianchi, Vittorio Locatelli, Laura Rizzi
INTRODUCTION: Human neurodegenerative diseases increase progressively with age and present a high social and economic burden. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are both growth factors exerting trophic effects on neuronal regeneration in the central nervous system (CNS) and peripheral nervous system (PNS). GH and IGF-1 stimulate protein synthesis in neurons, glia, oligodendrocytes, and Schwann cells, and favor neuronal survival, inhibiting apoptosis. This study aims to evaluate the effect of GH and IGF-1 on neurons, and their possible therapeutic clinical applications on neuron regeneration in human subjects...
November 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29105578/role-of-perforin-secretion-from-cd8-t-cells-in-neuronal-cytotoxicity-in-multiple-sclerosis
#11
Daidi Zhao, Fuqiang Feng, Cong Zhao, Fang Wu, Chao Ma, Yanan Bai, Jun Guo, Hongzeng Li
OBJECTIVES: Multiple sclerosis (MS) is the most prevalent autoimmune disease of the central nervous system, and is characterized by inflammation and myelin damage. The immune system initiates the autoimmune response, although the mechanisms of neuronal damage have not been elucidated. The purpose of the present study was to investigate autoreactive CD4+ and CD8(+) T lymphocytes, in conjunction with other inflammatory cells and cytokines in active MS lesions. METHODS: EAE animal models was established by plantar injections of MBP (200 μg per rat)...
November 5, 2017: Neurological Research
https://www.readbyqxmd.com/read/29104820/a-novel-animal-model-for-neuroinflammation-and-white-matter-degeneration
#12
Baohu Ji, Kerin Higa, Virawudh Soontornniyomkij, Atsushi Miyanohara, Xianjin Zhou
Small interference RNA has been widely used to suppress gene expression. Three different short hairpin RNAs (shRNAs) against dopamine D1 receptor (Drd1), driven by mouse U6 promoter in self-complementary AAV8 vector (scAAV8), were used to silence mouse striatal Drd1 expression. Transduction of mouse striatum with all three scAAV8-D1shRNA viruses, but not the control scAAV8 virus, causes extensive neuroinflammation, demyelination, and axon degeneration. RNA interference is known to be coupled to the innate immune system as a host cell defense against virus infection...
2017: PeerJ
https://www.readbyqxmd.com/read/29104236/the-emerging-role-of-the-major-histocompatibility-complex-class-i-in-amyotrophic-lateral-sclerosis
#13
REVIEW
Gabriela Bortolança Chiarotto, Giovanni Nardo, Maria Chiara Trolese, Marcondes Cavalcante França, Caterina Bendotti, Alexandre Leite Rodrigues de Oliveira
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting upper and lower motoneurons (MNs). The etiology of the disease is still unknown for most patients with sporadic ALS, while in 5-10% of the familial cases, several gene mutations have been linked to the disease. Mutations in the gene encoding Cu, Zn superoxide dismutase (SOD1), reproducing in animal models a pathological scenario similar to that found in ALS patients, have allowed for the identification of mechanisms relevant to the ALS pathogenesis...
November 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29103421/a-neuroprimer-principles-of-central-nervous-system-immunity
#14
Gregory P Owens
Despite longstanding perceptions, robust innate and adaptive immune responses occur within the central nervous system (CNS) in response to infection and tissue damage. Although necessary to control infection, immune responses can lead to severe CNS pathology in the context of both viral infection and autoimmunity. Research into how the central nervous and immune systems communicate has accelerated over the past 20 years leading to a better understanding of pathways controlling immune activation and neuroinflammation that have guided the approval of new disease-modifying therapies to treat CNS immunopathology, particularly the inflammatory demyelinating disease multiple sclerosis...
August 2017: Seminars in Pediatric Neurology
https://www.readbyqxmd.com/read/29101799/s-allyl-cysteine-improves-clinical-and-neuropathological-features-of-experimental-autoimmune-encephalomyelitis-in-c57bl-6-mice
#15
Hossein Zeinali, Tourandokht Baluchnejadmojarad, Soudabeh Fallah, Mohsen Sedighi, Nariman Moradi, Mehrdad Roghani
Multiple sclerosis (MS) is a deleterious autoimmune and demyelinating disorder of the central nervous system with debilitating sensory and motor complications. There is still no definite cure for it and the main focus for its treatment mostly pivots around subsiding its severity and recurrence. Experimental autoimmune encephalomyelitis (EAE) is an established animal model of MS. S-allyl cysteine (SAC) is the active and main constituent of aged garlic extract with anti-inflammatory and neuroprotective property...
November 1, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29101043/the-influence-and-impact-of-ageing-and-immunosenescence-isc-on-adaptive-immunity-during-multiple-sclerosis-ms-and-the-animal-counterpart-experimental-autoimmune-encephalomyelitis-eae
#16
REVIEW
Christopher Bolton, Paul A Smith
The human ageing process encompasses mechanisms that effect a decline in homeostasis with increased susceptibility to disease and the development of chronic life-threatening illness. Increasing age affects the immune system which undergoes a progressive loss of efficiency, termed immunosenescence (ISC), to impact on quantitative and functional aspects of innate and adaptive immunity. The human demyelinating disease multiple sclerosis (MS) and the corresponding animal model experimental autoimmune encephalomyelitis (EAE) are strongly governed by immunological events that primarily involve the adaptive arm of the immune response...
October 31, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/29099057/the-c-c-chemokines-ccl17-and-ccl22-and-their-receptor-ccr4-in-cns-autoimmunity
#17
REVIEW
Stefanie Scheu, Shafaqat Ali, Christina Ruland, Volker Arolt, Judith Alferink
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). It affects more than two million people worldwide, mainly young adults, and may lead to progressive neurological disability. Chemokines and their receptors have been shown to play critical roles in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a murine disease model induced by active immunization with myelin proteins or transfer of encephalitogenic CD4⁺ T cells that recapitulates clinical and neuropathological features of MS...
November 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29081780/deletion-of-the-mineralocorticoid-receptor-in-myeloid-cells-attenuates-central-nervous-system-autoimmunity
#18
Elena Montes-Cobos, Nils Schweingruber, Xiao Li, Henrike J Fischer, Holger M Reichardt, Fred Lühder
Myeloid cells play an important role in the pathogenesis of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Monocytes, macrophages, and microglia can adopt two distinct phenotypes, with M1-polarized cells being more related to inflammation and autoimmunity while M2-polarized cells contribute to tissue repair and anti-inflammatory processes. Here, we show that deletion of the mineralocorticoid receptor (MR) in bone marrow-derived macrophages and peritoneal macrophages caused their polarization toward the M2 phenotype with its distinct gene expression, altered phagocytic and migratory properties, and dampened NO production...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29081600/amyotrophic-lateral-sclerosis-a-multisystem-pathology-insights-into-the-role-of-tnf%C3%AE
#19
REVIEW
Massimo Tortarolo, Daniele Lo Coco, Pietro Veglianese, Antonio Vallarola, Maria Teresa Giordana, Gabriella Marcon, Ettore Beghi, Marco Poloni, Michael J Strong, Anand M Iyer, Eleonora Aronica, Caterina Bendotti
Amyotrophic lateral sclerosis (ALS) is considered a multifactorial, multisystem disease in which inflammation and the immune system play important roles in development and progression. The pleiotropic cytokine TNFα is one of the major players governing the inflammation in the central nervous system and peripheral districts such as the neuromuscular and immune system. Changes in TNFα levels are reported in blood, cerebrospinal fluid, and nerve tissues of ALS patients and animal models. However, whether they play a detrimental or protective role on the disease progression is still not clear...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29053787/humanized-mutant-fus-drives-progressive-motor-neuron-degeneration-without-aggregation-in-fusdelta14-knockin-mice
#20
Anny Devoy, Bernadett Kalmar, Michelle Stewart, Heesoon Park, Beverley Burke, Suzanna J Noy, Yushi Redhead, Jack Humphrey, Kitty Lo, Julian Jaeger, Alan Mejia Maza, Prasanth Sivakumar, Cinzia Bertolin, Gianni Soraru, Vincent Plagnol, Linda Greensmith, Abraham Acevedo Arozena, Adrian M Isaacs, Benjamin Davies, Pietro Fratta, Elizabeth M C Fisher
Mutations in FUS are causative for amyotrophic lateral sclerosis with a dominant mode of inheritance. In trying to model FUS-amyotrophic lateral sclerosis (ALS) in mouse it is clear that FUS is dosage-sensitive and effects arise from overexpression per se in transgenic strains. Novel models are required that maintain physiological levels of FUS expression and that recapitulate the human disease-with progressive loss of motor neurons in heterozygous animals. Here, we describe a new humanized FUS-ALS mouse with a frameshift mutation, which fulfils both criteria: the FUS Delta14 mouse...
November 1, 2017: Brain: a Journal of Neurology
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