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Multiple sclerosis

Mathieu Marella, Laurence Jadin, Gilbert A Keller, Barry J Sugarman, Gregory I Frost, H Michael Shepard
Objective: Modification of hyaluronan (HA) accumulation has been shown to play a key role in regulating inflammatory processes linked to the progression of multiple sclerosis (MS). The aim of this study was to characterize the enzymatic activity involved in HA degradation observed within focal demyelinating lesions in the experimental autoimmune encephalomyelitis (EAE) animal model. Methods: EAE was induced in 3-month-old female C57BL/6J mice by immunization with myelin oligodendrocyte glycoprotein 33-35 (MOG33-35) peptide...
July 7, 2018: Glycobiology
Erik Landfeldt, Anna Castelo-Branco, Axel Svedbom, Emil Löfroth, Andrius Kavaliunas, Jan Hillert
BACKGROUND: Several studies have investigated the impact of multiple sclerosis (MS) on the risk of divorce. However, current evidence is inconclusive and limited by e.g. small sample populations, short follow-up, and/or lack of a control group. The objective of this retrospective, observational study was to estimate the long-term impact of MS on the risk of divorce. METHODS: Swedish patients diagnosed with MS between 1975 and 2012 were identified in a nationwide disease-specific register (the Swedish Multiple Sclerosis Registry) and matched with general population controls based on age, sex, region of residency, and marital status...
July 3, 2018: Multiple Sclerosis and related Disorders
Alia Saberi, Shahin Akhondzadeh, Samaneh Kazemi
Multiple sclerosis (MS) causes demyelination of white matter of central nervous system and neuro-degeneration due to inflammation. Different types of MS, as well as disease progression, come with different pathology and pathophysiology. The objective of this study was to evaluate the possible association between different micro-organisms and the relapse or progression of MS. Studies indexed in Medline/PMC, Scopus and Web of Science published without time and language limitation until March 2017 were identified through the search terms "infection" or "infectious" and "multiple sclerosis"...
July 13, 2018: Acta Neurologica Belgica
Alexandru Tatomir, Cosmin A Tegla, Alvaro Martin, Dallas Boodhoo, Vinh Nguyen, Adam J Sugarman, Armugam Mekala, Freidrich Anselmo, Anamaria Talpos-Caia, Cornelia Cudrici, Tudor C Badea, Violeta Rus, Horea Rus
Extracellular matrix (ECM) deposition in active demyelinating multiple sclerosis (MS) lesions may impede axonal regeneration and can modify immune reactions. Response gene to complement (RGC)-32 plays an important role in the mediation of TGF-β downstream effects, but its role in gliosis has not been investigated. To gain more insight into the role played by RGC-32 in gliosis, we investigated its involvement in TGF-β-induced ECM expression and the upregulation of the reactive astrocyte markers α-smooth muscle actin (α-SMA) and nestin...
July 13, 2018: Immunologic Research
Chenyi Wang, Mark R Kotter
Multiple sclerosis (MS) is a chronic autoimmune, inflammatory disease in the central nervous system (CNS) characterized by loss of oligodendrocytes, myelin axons, and neurons. Remyelination is an endogenous repair mechanism, which recovers the loss of myelin and is able to preserve functional axons. The hope is that the development of new treatments aiming at promoting remyelination will halt and potentially partially reverse the progressive neurological decline in MS. The development of such drugs requires adequate models...
2018: Methods in Molecular Biology
Mercedes Giralt, Amalia Molinero, Juan Hidalgo
Experimental autoimmune encephalomyelitis (EAE) is one of the most popular animal models of multiple sclerosis (MS). There are a number of EAE models, being actively induced EAE in strains such as C57Bl/6 mice very robust and reproducible. We herewith present details of the materials and methods for active EAE. Mice are immunized with an emulsion of myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55 ) + complete Freund's adjuvant (supplemented with Mycobacterium tuberculosis), and treated with Bordetella pertussis toxin, to induce EAE...
2018: Methods in Molecular Biology
Karen Lariosa-Willingham, Dmitri Leonoudakis
The formation of new myelin in persistent multiple sclerosis (MS) lesions is compromised, leading to a reduction in neuron function and subject to degeneration and death. Current MS therapies can control autoimmune-mediated demyelination, but none directly promote the regeneration of myelin in the central nervous system (CNS). To identify new drugs that stimulate remyelination, we established a high-throughput cell-based assay to identify compounds that promote myelination. Methods were developed for initiating myelination in vitro using a preparation of primary embryonic rat cortical cells...
2018: Methods in Molecular Biology
Maria Victoria Sánchez-Gómez, Mari Paz Serrano, Elena Alberdi, Fernando Pérez-Cerdá, Carlos Matute
Oligodendrocytes are the myelin-forming cells in the central nervous system (CNS) and their loss or dysfunction is a hallmark of CNS demyelinating diseases, such as multiple sclerosis (MS), hypoxic-ischemic demyelination, or spinal cord injury. In the rodent CNS, oligodendrocyte progenitor cells (OPCs) arise in multiple ventral and dorsal locations of the forebrain during late embryogenesis and early postnatal periods. OPCs migrate out from these germinal zones and disperse throughout the CNS, to populate the developing white and gray matter...
2018: Methods in Molecular Biology
Josianne C Ten Berge, Marco Wj Schreurs, Joost van Rosmalen, Aniki Rothova
A high prevalence of serum antiretinal antibodies (ARAs) in patients with uveitis has been previously described, though their clinical role remains elusive. Assessment of intraocular ARAs may provide further insight into the pathogenesis of diverse uveitis entities. In this study we investigate the prevalence of multiple specific anti-ocular antibodies (AOcAs), including ARAs, in intraocular fluid of patients with uveitis. Autoantibody profiling with 188 different ocular antigens was performed by a multiplex immunoassay with intraocular fluid samples of 76 patients with uveitis...
July 10, 2018: Experimental Eye Research
Nikita A Mitkin, Alisa M Muratova, Kirill V Korneev, Vsevolod V Pavshintsev, Konstantin A Rumyantsev, Murad S Vagida, Aksinya N Uvarova, Marina A Afanasyeva, Anton M Schwartz, Dmitry V Kuprash
CD58 is expressed on the surface of antigen-presenting cells, including B-cells, and provides co-stimulation to regulatory T-cells (Treg) through CD2 receptor binding. Tregs appear to be essential suppressors of tissue-specific autoimmune responses. Thereby, CD58 plays protective role in multiple sclerosis (MS) and CD58 was identified among several loci associated with MS susceptibility. Minor (C) variant of the single-nucleotide polymorphism (SNP) rs1335532 is associated with lower MS risk according to genome-wide association studies (GWAS) and its presence correlates with higher CD58 mRNA levels in MS patients...
July 10, 2018: Biochimica et Biophysica Acta
Wei Chen, Rafik M Ghobrial, Xian C Li, Malgorzata Kloc
Macrophage functions in the immune response depend on their ability to infiltrate tissues and organs. The penetration between and within the tissues requires degradation of extracellular matrix (ECM), a function performed by the specialized, endopeptidase- and actin filament- rich organelles located at the ventral surface of macrophage, called the podosomes. Podosome formation requires local inhibition of small GTPase RhoA activity, and depends on Rac 1/Rho guanine nucleotide exchange factor 7, β-PIX and its binding partner the p21-activated kinase (PAK-1)...
July 7, 2018: Immunobiology
I Sanz Pérez, F Martínez Valle, A Guillén Del Castillo, A Roque Pérez, H Cuéllar Calàbria, M N Pizzi, A Fernández Codina, E Callejas Moragas, O Orozco Gálvez, V Fonollosa Pla, C P Simeón Aznar
BACKGROUND AND OBJECTIVES: Recently published population-based cohort studies have shown a high prevalence of cardiovascular disease in Systemic Sclerosis (SSc) patients. The aim of this study is to compare three different methods to measure cardiovascular risk in patients with scleroderma. METHODS: Forty-three SSc patients were included. A prospective study was performed for evaluation of cardiovascular risk and subclinical atheromatosis using 3 non-invasive methods: cardiovascular risk tables, carotid Doppler ultrasonography and quantification of coronary calcium by computerized tomography (CT)...
July 10, 2018: Autoimmunity Reviews
Darcy A Krueger, Jamie K Capal, Paolo Curatolo, Orrin Devinsky, Kevin Ess, Michal Tzadok, Mary K Koenig, Vinodh Narayanan, Federico Ramos, Sergiusz Jozwiak, Petrus de Vries, Anna C Jansen, Michael Wong, David Mowat, John Lawson, Stephanie Bruns, David Neal Franz
OBJECTIVE: To evaluate the safety of mTOR inhibitors (sirolimus or everolimus) in infants and very young children with tuberous sclerosis complex (TSC) under two years of age. METHODS: Study design was retrospective to capture medical record data from 52 international TSC Centres who initiated treatment with sirolimus or everolimus in TSC children before the age of two years. Data collection included demographic and clinical information including reason(s) for initiating treatment with mTOR inhibitors, treatment duration, dosing, and corresponding serum trough levels, response to treatment, and adverse events (AE)...
July 4, 2018: European Journal of Paediatric Neurology: EJPN
Gurpreet K Reen, Eli Silber, Dawn W Langdon
BACKGROUND: Patients' understanding of treatment risks and benefits is a prerequisite for shared decision making. Yet, patients with multiple sclerosis (MS) do not accurately understand treatment information provided in regular clinical consultations. OBJECTIVES: To identify the best methods of communicating clinical trial data to improve the understanding of treatments among patients with MS and to also examine the relationship between patients' understanding with decisional conflict, individual traits, and MS symptoms...
July 2018: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
Ellen M Mowry, Anna K Hedström, Milena A Gianfrancesco, Xiaorong Shao, Catherine A Schaefer, Ling Shen, Kalliope H Bellesis, Farren B S Briggs, Tomas Olsson, Lars Alfredsson, Lisa F Barcellos
BACKGROUND: Multiple sclerosis (MS) incidence has increased recently, particularly in women, suggesting a possible role of one or more environmental exposures in MS risk. The study objective was to determine if animal, dietary, recreational, or occupational exposures are associated with MS risk. METHODS: Least absolute shrinkage and selection operator (LASSO) regression was used to identify a subset of exposures with potential relevance to disease in a large population-based (Kaiser Permanente Northern California [KPNC]) case-control study...
June 23, 2018: Multiple Sclerosis and related Disorders
Peter Vestergaard Rasmussen, Melinda Magyari, Julie Yoon Moberg, Mette Bøgelund, Ulla Fie Appel Jensen, Klaus Gregaard Madsen
BACKGROUND: The purpose of the survey was to assess the knowledge of family planning issues associated with disease modifying therapies (DMTs) among patients diagnosed with multiple sclerosis (MS). METHODS: 590 Danish MS patients responded to an online questionnaire about family planning in MS, collecting demographics, disease characteristics, disease modifying treatment, knowledge of potential teratogenic effects in DMTs, number of children, occurrence of unplanned pregnancies and outcome, and sources of information...
June 15, 2018: Multiple Sclerosis and related Disorders
Caterina Sarnicola, Asim V Farooq, Kathryn Colby
Fuchs endothelial corneal dystrophy (FECD) is the most common indication for corneal transplantation in the United States, accounting 36% of the almost 47,000 transplants performed in 2016. Although the surgical management of FECD has undergone a revolution over the past 20 years, its pathogenesis remains elusive, with multiple putative disease pathways and an ever increasing number of candidate genes thought to play a role. This review will summarize the recent advancements in our understanding of the biology of FECD, including potential parallels with neurodegenerative disease like amyotrophic lateral sclerosis and will highlight prospects for future treatment advances...
July 12, 2018: Eye & Contact Lens
Edgar Carnero Contentti, Mariana De Virgiliis, Javier Pablo Hryb, Alejandra Gomez, Sergio Morales, Julia Celso, Felisa Leguizamón, Edson Chiganer, José Luis Di Pace, Carmen Lessa, Mónica Perassolo
BACKGROUND: Aquaporin-4 antibodies (AQP4-Ab) are associated with neuromyelitis optica spectrum disorder (NMOSD) and typically this disorder has a poor visual prognosis as a result of optic neuritis (ON). Our aim was to report the clinical features at onset and final visual outcomes at 6 months of patients with ON who were positive for AQP4-Ab vs. those who were negative for AQP4-Ab. METHODS: Retrospective cohort study. AQP4-Ab were tested by indirect immunofluorescence in 57 patients with a first episode of ON...
July 12, 2018: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
Tarun Singhal, Kelsey OʼConnor, Shipra Dubey, Anthony P Belanger, Shelley Hurwitz, Renxin Chu, Shahamat Tauhid, Marie F Kijewski, Marcelo F DiCarli, Howard L Weiner, Rohit Bakshi
BACKGROUND AND PURPOSE: F-PBR06 and C-PBR28 are second-generation PET radioligands targeting the 18-kd translocator protein to assess microglial activation. We directly compared F-PBR06 and C-PBR28 for detecting brain translocator protein binding in multiple sclerosis (MS). METHODS: Six patients with MS (4 women; mean age ± SD, 32.1 ± 4.9 [range, 23.5-37.4 years]; Expanded Disability Status Scale score 2.3 ± 1.2 [range, 1.0-4.0]) underwent brain PET with both ligands, along with 3-T MRI...
July 12, 2018: Clinical Nuclear Medicine
Mustafa Sertbas, Kutlu O Ulgen
Neurology research and clinical practice are transforming toward postgenomics integrative biology. One such example is the study of human brain metabolism that is highly sophisticated due to reactions occurring in and between the astrocytes and neurons. Because of the inherent difficulty of performing experimental studies in human brain, metabolic network modeling has grown in importance to decipher the contribution of brain metabolite kinetics to human health and disease. Multiomics system science-driven metabolic models, using genome-scale and transcriptomics Big Data, offer the promise of new insights on metabolic networks in human brain...
July 2018: Omics: a Journal of Integrative Biology
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