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Multiple sclerosis and iron

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https://www.readbyqxmd.com/read/29021778/the-combined-quantification-and-interpretation-of-multiple-quantitative-magnetic-resonance-imaging-metrics-enlightens-longitudinal-changes-compatible-with-brain-repair-in-relapsing-remitting-multiple-sclerosis-patients
#1
Guillaume Bonnier, Benedicte Maréchal, Mário João Fartaria, Pavel Falkowskiy, José P Marques, Samanta Simioni, Myriam Schluep, Renaud Du Pasquier, Jean-Philippe Thiran, Gunnar Krueger, Cristina Granziera
OBJECTIVE: Quantitative and semi-quantitative MRI (qMRI) metrics provide complementary specificity and differential sensitivity to pathological brain changes compatible with brain inflammation, degeneration, and repair. Moreover, advanced magnetic resonance imaging (MRI) metrics with overlapping elements amplify the true tissue-related information and limit measurement noise. In this work, we combined multiple advanced MRI parameters to assess focal and diffuse brain changes over 2 years in a group of early-stage relapsing-remitting MS patients...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28980128/changes-in-routine-laboratory-tests-and-survival-in-amyotrophic-lateral-sclerosis
#2
Jessica Mandrioli, Edoardo Rosi, Nicola Fini, Antonio Fasano, Silvia Raggi, Anna Laura Fantuzzi, Giorgio Bedogni
The aim of this study is to evaluate the association between changes in routinely prescribed laboratory tests and tracheostomy-free survival in amyotrophic lateral sclerosis (ALS). Two hundred seventy-five ALS patients were retrospectively studied. BMI, forced vital capacity, hemoglobin, hematocrit, lymphocytes, cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, proteins, albumin, creatine-phosphokinase, iron, ferritin, transferrin, glucose, urea, uric acid, and creatinine were measured every 6 months from baseline to 24 months, death or study end, together with the probability of death or tracheostomy...
October 4, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28966637/metabolic-pathways-as-possible-therapeutic-targets-for-progressive-multiple-sclerosis
#3
REVIEW
Rebecca M Heidker, Mitchell R Emerson, Steven M LeVine
Unlike relapsing remitting multiple sclerosis, there are very few therapeutic options for patients with progressive forms of multiple sclerosis. While immune mechanisms are key participants in the pathogenesis of relapsing remitting multiple sclerosis, the mechanisms underlying the development of progressive multiple sclerosis are less well understood. Putative mechanisms behind progressive multiple sclerosis have been put forth: insufficient energy production via mitochondrial dysfunction, activated microglia, iron accumulation, oxidative stress, activated astrocytes, Wallerian degeneration, apoptosis, etc...
August 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28915963/hepcidin-and-metallothioneins-as-molecular-base-for-sex-dependent-differences-in-clinical-course-of-experimental-autoimmune-encephalomyelitis-in-chronic-iron-overload
#4
Božena Ćurko-Cofek, Tanja Grubić Kezele, Vesna Barac-Latas
Multiple sclerosis is a chronic demyelinating disease of the central nervous system characterised by inflammatory and degenerative changes. It is considered that disease arises from the influence of environmental factors on genetically susceptible individuals. Recent researches, using magnetic resonance imaging, connected iron deposits in different brain regions with demyelinating process in multiple sclerosis patients. Although iron is an essential trace element important for many biological functions it could be harmful because iron excess can induce the production of reactive oxygen species, development of oxidative stress and lipid peroxidation which leads to demyelination...
September 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28914166/repeated-iron-soot-exposure-and-nose-to-brain-transport-of-inhaled-ultrafine-particles
#5
Laurie E Hopkins, Emilia A Laing, Janice L Peake, Dale Uyeminami, Savannah M Mack, Xueting Li, Suzette Smiley-Jewell, Kent E Pinkerton
Particulate exposure has been implicated in the development of a number of neurological maladies such as multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, and idiopathic Parkinson's disease. Only a few studies have focused on the olfactory pathway as a portal through which combustion-generated particles may enter the brain. The primary objective of this study was to define the deposition, uptake, and transport of inhaled ultrafine iron-soot particles in the nasal cavities of mice to determine whether combustion-generated nanoparticles reach the olfactory bulb via the olfactory epithelium and nerve fascicles...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28863941/potential-role-of-ferric-hemoglobin-in-ms-pathogenesis-effects-of-oxidative-stress-and-extracellular-methemoglobin-or-its-degradation-products-on-myelin-components
#6
Vladimir V Bamm, Mary E L Henein, Shannon L J Sproul, Danielle K Lanthier, George Harauz
There is a well-documented relationship between cerebral vasculature and multiple sclerosis (MS) lesions: abnormal accumulations of iron have been found in the walls of the dilated veins in cerebral MS plaques. The source of this iron is unknown, but could be related to the recognized phenomenon of capillary and venous hemorrhages leading to blood extravasation. In turn, hemorrhaging leading to hemolysis results in extracellular release of hemoglobin, a reactive molecule that could induce local oxidative stress, inflammation, and tissue damage...
August 31, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28857721/unexpected-additive-effects-of-minocycline-and-hydroxychloroquine-in-models-of-multiple-sclerosis-prospective-combination-treatment-for-progressive-disease
#7
Simon Faissner, Yasamin Mahjoub, Manoj Mishra, Steffen Haupeltshofer, Jennifer Nancy Hahn, Ralf Gold, Marcus Koch, Luanne M Metz, Tamir Ben-Hur, V Wee Yong
BACKGROUND: Most multiple sclerosis (MS) patients succumb to a progressive phenotype. Continued lymphocyte activity in the brain, microglia-mediated injury, iron deposition, and oxidative stress are characteristics of progressive MS. OBJECTIVE: As minocycline and hydroxychloroquine have been shown to inhibit microglia, we evaluated their effects on other outcomes relevant for progression. METHODS: Medications were evaluated in culture and in mice with acute and chronic experimental autoimmune encephalomyelitis (EAE)...
August 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28808201/thalamic-paramagnetic-iron-by-t2-relaxometry-correlates-with-severity-of-multiple-sclerosis
#8
Eva Baranovicova, Ema Kantorova, Dagmar Kalenska, Lucia Lichardusova, Michal Bittsan-Sky, Dusan Dobrota
Iron can contribute to the pathogenesis and progression of multiple sclerosis (MS) due to its accumulation in the human brain. We focus on the thalamus as an information transmitter between various subcortical and cortical areas. Thalamic iron seems to follow different rules than iron in other deep gray matter structures and its relation to the clinical outcomes of MS is still indistinct. In our study, we investigated a connection between thalamic iron and patients' disability and course of the disease. The presence of paramagnetic substances in the tissues was tracked by T2* quantification...
July 13, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28803512/heterogeneous-pathological-processes-account-for-thalamic-degeneration-in-multiple-sclerosis-insights-from-7%C3%A2-t-imaging
#9
Céline Louapre, Sindhuja T Govindarajan, Costanza Giannì, Nancy Madigan, Jacob A Sloane, Constantina A Treaba, Elena Herranz, Revere P Kinkel, Caterina Mainero
BACKGROUND: Thalamic degeneration impacts multiple sclerosis (MS) prognosis. OBJECTIVE: To investigate heterogeneous thalamic pathology, its correlation with white matter (WM), cortical lesions and thickness, and as function of distance from cerebrospinal fluid (CSF). METHODS: In 41 MS subjects and 17 controls, using 3 and 7 T imaging, we tested for (1) differences in thalamic volume and quantitative T2* (q-T2*) (2) globally and (3) within concentric bands originating from the CSF/thalamus interface; (4) the relation between thalamic, cortical, and WM metrics; and (5) the contribution of magnetic resonance imaging (MRI) metrics to clinical scores...
August 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28744286/a-b-cell-driven-autoimmune-pathway-leading-to-pathological-hallmarks-of-progressive-multiple-sclerosis-in-the-marmoset-experimental-autoimmune-encephalomyelitis-model
#10
REVIEW
Bert A 't Hart, Jordon Dunham, Bart W Faber, Jon D Laman, Jack van Horssen, Jan Bauer, Yolanda S Kap
The absence of pathological hallmarks of progressive multiple sclerosis (MS) in commonly used rodent models of experimental autoimmune encephalomyelitis (EAE) hinders the development of adequate treatments for progressive disease. Work reviewed here shows that such hallmarks are present in the EAE model in marmoset monkeys (Callithrix jacchus). The minimal requirement for induction of progressive MS pathology is immunization with a synthetic peptide representing residues 34-56 from human myelin oligodendrocyte glycoprotein (MOG) formulated with a mineral oil [incomplete Freund's adjuvant (IFA)]...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28705068/quantifying-the-susceptibility-variation-of-normal-appearing-white-matter-in-multiple-sclerosis-by-quantitative-susceptibility-mapping
#11
Weiwei Chen, Yan Zhang, Ketao Mu, Chu Pan, Susan A Gauthier, Wenzhen Zhu, Yi Wang
OBJECTIVE: The purpose of this study is to evaluate the magnetic susceptibility of normal-appearing white matter (NAWM) in patients with multiple sclerosis (MS) using quantitative susceptibility mapping. MATERIALS AND METHODS: Ninety-four patients with relapse-remitting MS (RRMS) (37 with gadolinium-enhancing lesions and 57 with only gadolinium-nonenhancing lesions) and 55 healthy control subjects were included in this retrospective study. The susceptibility values of NAWM relative to CSF in patients with MS were compared with those of white matter (WM) in healthy control subjects and were correlated with the patient status of gadolinium-enhancing lesions, disease duration, and expanded disability status scale scores...
October 2017: AJR. American Journal of Roentgenology
https://www.readbyqxmd.com/read/28675556/prospective-clinical-trials-to-investigate-clinical-and-molecular-biomarkers
#12
REVIEW
Stéphane Auvin, Lauren Walker, William Gallentine, Sergiusz Jozwiak, Mario Tombini, Graeme J Sills
Among clinical studies, randomized studies as well as well-designed observational studies are providing the highest quality data. In addition, these studies represent a good opportunity to examine biomarkers of ictogenesis and epileptogenesis. To date, no validated molecular or cellular biomarker exists for any aspect of epilepsy. We provide an overview of the inflammatory biomarkers under investigation in prospective clinical studies in epilepsy: proinflammatory cytokines in prolonged febrile seizure; High Mobility Group Box 1 (HMGB1) as a prognosis biomarker in epilepsy and the interaction between inflammation and metabolism, in particular, iron metabolism, in epilepsy...
July 2017: Epilepsia
https://www.readbyqxmd.com/read/28620346/primary-progressive-multiple-sclerosis-putting-together-the-puzzle
#13
REVIEW
Ahmed Abdelhak, Martin S Weber, Hayrettin Tumani
The focus of multiple sclerosis research has recently turned to the relatively rare and clearly more challenging condition of primary progressive multiple sclerosis (PPMS). Many risk factors such as genetic susceptibility, age, and Epstein-Barr virus (EBV) infection may interdepend on various levels, causing a complex pathophysiological cascade. Variable pathological mechanisms drive disease progression, including inflammation-associated axonal loss, continuous activation of central nervous system resident cells, such as astrocytes and microglia as well as mitochondrial dysfunction and iron accumulation...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28618115/iron-sulfur-glutaredoxin-2-protects-oligodendrocytes-against-damage-induced-by-nitric-oxide-release-from-activated-microglia
#14
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...
September 2017: Glia
https://www.readbyqxmd.com/read/28618066/assessment-of-ferritin-content-in-multiple-sclerosis-brains-using-temperature-induced-r-2-changes
#15
Christoph Birkl, Daniele Carassiti, Fariha Hussain, Christian Langkammer, Christian Enzinger, Franz Fazekas, Klaus Schmierer, Stefan Ropele
PURPOSE: Current MRI techniques cannot reliably assess iron content in white matter due to the confounding diamagnetic effect of myelin. The purpose of this study was to validate with histology a novel iron mapping technique that uses the temperature dependency of the paramagnetic susceptibility in multiple sclerosis (MS) brains, where white matter has been reported to show significant variations in iron content. METHODS: We investigated post mortem brain tissue from three MS patients and one control subject...
June 15, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28608728/dietary-factors-and-pediatric-multiple-sclerosis-a-case-control-study
#16
Julia Pakpoor, Brandon Seminatore, Jennifer S Graves, Teri Schreiner, Amy T Waldman, Timothy E Lotze, Anita Belman, Benjamin M Greenberg, Bianca Weinstock-Guttman, Gregory Aaen, Jan-Mendelt Tillema, Jamie C McDonald, Janace Hart, Jayne M Ness, Yolanda Harris, Jennifer Rubin, Meghan Candee, Lauren Krupp, Mark Gorman, Leslie Benson, Moses Rodriguez, Tanuja Chitnis, Soe Mar, Ilana Kahn, John Rose, Suzan L Carmichael, Shelly Roalstad, Michael Waltz, T Charles Casper, Emmanuelle Waubant
BACKGROUND: The role of diet in multiple sclerosis (MS) is largely uncharacterized, particularly as it pertains to pediatric-onset disease. OBJECTIVE: To determine the association between dietary factors and MS in children. METHODS: Pediatric MS patients and controls were recruited from 16 US centers (MS or clinically isolated syndrome onset before age 18, <4 years from symptom onset and at least 2 silent lesions on magnetic resonance imaging)...
June 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28546762/cardiovascular-magnetic-resonance-imaging-clinical-implications-in-the-evaluation-of-connective-tissue-diseases
#17
REVIEW
Sophie Mavrogeni, George Markousis-Mavrogenis, Loukia Koutsogeorgopoulou, Genovefa Kolovou
Cardiovascular magnetic resonance imaging is a recently developed noninvasive, nonradiating, operator-independent technique that has been successfully used for the evaluation of congenital heart disease, valvular and pericardial diseases, iron overload, cardiomyopathies, great and coronary vessel diseases, cardiac inflammation, stress-rest myocardial perfusion, and fibrosis. Rheumatoid arthritis and other spondyloarthropathies, systemic lupus erythematosus, inflammatory myopathies, mixed connective tissue diseases (CTDs), systemic sclerosis, vasculitis, and sarcoidosis are among CTDs with serious cardiovascular involvement; this is due to multiple causative factors such as myopericarditis, micro/macrovascular disease, coronary artery disease, myocardial fibrosis, pulmonary hypertension, and finally heart failure...
2017: Journal of Inflammation Research
https://www.readbyqxmd.com/read/28509815/serum-iron-concentration-is-associated-with-subcortical-deep-gray-matter-iron-levels-in-multiple-sclerosis-patients
#18
Niels Bergsland, Simone Agostini, Maria M Laganà, Roberta Mancuso, Laura Mendozzi, Eleonora Tavazzi, Pietro Cecconi, Mario Clerici, Francesca Baglio
Iron deposition has been noted widely in the subcortical deep gray matter (SDGM) of multiple sclerosis (MS) patients. Recent evidence suggests that serum iron may cross the blood-brain barrier and might be associated with SDGM iron deposition. The aim of the current study was to assess whether an iron-sensitive MRI measure is related to serum iron concentrations. This was a retrospective, cross-sectional study of 22 MS patients and 24 healthy controls (HCs), group matched for age and sex. Participants were imaged on a 1...
August 2, 2017: Neuroreport
https://www.readbyqxmd.com/read/28505283/oxidative-injury-and-iron-redistribution-are-pathological-hallmarks-of-marmoset-experimental-autoimmune-encephalomyelitis
#19
Jordon Dunham, Jan Bauer, Graham R Campbell, Don J Mahad, Nikki van Driel, Susanne M A van der Pol, Bert A 't Hart, Hans Lassmann, Jon D Laman, Jack van Horssen, Yolanda S Kap
Oxidative damage and iron redistribution are associated with the pathogenesis and progression of multiple sclerosis (MS), but these aspects are not entirely replicated in rodent experimental autoimmune encephalomyelitis (EAE) models. Here, we report that oxidative burst and injury as well as redistribution of iron are hallmarks of the MS-like pathology in the EAE model in the common marmoset. Active lesions in the marmoset EAE brain display increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p22phox, p47phox, and gp91phox) and inducible nitric oxide synthase immunoreactivity within lesions with active inflammation and demyelination, coinciding with enhanced expression of mitochondrial heat-shock protein 70 and superoxide dismutase 1 and 2...
June 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28470768/susceptibility-sensitive-mri-of-multiple-sclerosis-lesions-and-the-impact-of-normal-appearing-white-matter-changes
#20
Vanessa Wiggermann, Simon Hametner, Enedino Hernández-Torres, Christian Kames, Verena Endmayr, Gregor Kasprian, Romana Höftberger, David K B Li, Anthony Traboulsee, Alexander Rauscher
Susceptibility-sensitive magnetic resonance imaging (MRI) has gained importance in multiple sclerosis (MS) research because of its versatility, high resolution and excellent sensitivity to changes in tissue structure and composition. In particular, mapping of the resonance frequency of the MR signal and quantitative susceptibility mapping (QSM) have been explored for the description of MS lesions. Many current studies utilizing these techniques attribute increases in the MR frequency or QSM to elevated tissue iron content, in addition to myelin loss...
August 2017: NMR in Biomedicine
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