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Multiple sclerosis and iron

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https://www.readbyqxmd.com/read/29205982/spasticity-or-periodic-limb-movements
#1
Jonathan Levy, Sarah Hartley, Elsa Mauruc-Soubirac, Antoine Leotard, Frederic Lofaso, Maria-Antonia Quera-Salva, Djamel Bensmail
BACKGROUND: Spasticity and spasms are distressing features of the upper motor neuron syndrome (UMNS) following spinal cord injuries (SCI) or multiple sclerosis (MS), and have common therapeutic implications. Despite an increase of antispastic drugs and strategies, sometimes up to the surgical implant of intrathecal baclofen pump, some patients still complain of disabling spasms, which poses diagnostic and therapeutic challenges. Although clinically similar, flexor spasms due to pyramidal tract disruption must be clearly differentiated from periodic limb movements (PLM), often accompanying restless leg syndrome (RLS) and occurring during sleep...
December 4, 2017: European Journal of Physical and Rehabilitation Medicine
https://www.readbyqxmd.com/read/29201641/iron-related-gene-variants-and-brain-iron-in-multiple-sclerosis-and-healthy-individuals
#2
Jesper Hagemeier, Murali Ramanathan, Ferdinand Schweser, Michael G Dwyer, Fuchun Lin, Niels Bergsland, Bianca Weinstock-Guttman, Robert Zivadinov
Brain iron homeostasis is known to be disturbed in multiple sclerosis (MS), yet little is known about the association of common gene variants linked to iron regulation and pathological tissue changes in the brain. In this study, we investigated the association of genetic determinants linked to iron regulation with deep gray matter (GM) magnetic susceptibility in both healthy controls (HC) and MS patients. Four hundred (400) patients with MS and 150 age- and sex-matched HCs were enrolled and obtained 3 T MRI examination...
2018: NeuroImage: Clinical
https://www.readbyqxmd.com/read/29185388/%C3%AE-lipoic-acid-functional-fatty-acid-as-a-novel-therapeutic-alternative-for-central-nervous-system-diseases-a-review
#3
Fatemeh Seifar, Mohammad Khalili, Habib Khaledyan, Shirin Amiri Moghadam, Azimeh Izadi, Amirreza Azimi, Seied Kazem Shakouri
OBJECTIVES: α-lipoic acid (ALA) is a natural antioxidant which acts as a cofactor of bioenergetic mitochondrial enzymes. Along with its mitochondrial action, ALA and its reduced form have many biological functions resulting in a wide variety of actions such as anti-inflammation and antioxidant protection, scavenging reactive oxygen species, regenerating other antioxidant agents, such as vitamins C and E, and cytosolic glutathione, chelating the transitional metal ions (e.g. iron and copper), and modulating the signal transduction of nuclear factor...
November 29, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/29136024/severe-oxidative-stress-in-an-acute-inflammatory-demyelinating-model-in-the-rhesus-monkey
#4
Jordon Dunham, Reinofke van de Vis, Jan Bauer, Jacqueline Wubben, Nikki van Driel, Jon D Laman, Bert A 't Hart, Yolanda S Kap
Oxidative stress is increasingly implicated as a co-factor of tissue injury in inflammatory/demyelinating disorders of the central nervous system (CNS), such as multiple sclerosis (MS). While rodent experimental autoimmune encephalomyelitis (EAE) models diverge from human demyelinating disorders with respect to limited oxidative injury, we observed that in a non-human primate (NHP) model for MS, namely EAE in the common marmoset, key pathological features of the disease were recapitulated, including oxidative tissue injury...
2017: PloS One
https://www.readbyqxmd.com/read/29097315/mapping-of-thalamic-magnetic-susceptibility-in-multiple-sclerosis-indicates-decreasing-iron-with-disease-duration-a-proposed-mechanistic-relationship-between-inflammation-and-oligodendrocyte-vitality
#5
Ferdinand Schweser, Ana Luiza Raffaini Duarte Martins, Jesper Hagemeier, Fuchun Lin, Jannis Hanspach, Bianca Weinstock-Guttman, Simon Hametner, Niels P Bergsland, Michael G Dwyer, Robert Zivadinov
Recent advances in susceptibility MRI have dramatically improved the visualization of deep gray matter brain regions and the quantification of their magnetic properties in vivo, providing a novel tool to study the poorly understood iron homeostasis in the human brain. In this study, we used an advanced combination of the recent quantitative susceptibility mapping technique with dedicated analysis methods to study intra-thalamic tissue alterations in patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS)...
October 30, 2017: NeuroImage
https://www.readbyqxmd.com/read/29064775/uspio-positive-ms-lesions-are-associated-with-greater-tissue-damage-than-gadolinium-positive-only-lesions-during-3-year-follow-up
#6
Anne Kerbrat, Benoit Combès, Olivier Commowick, Adil Maarouf, Elise Bannier, Jean Christophe Ferré, Ayman Tourbah, Jean-Philippe Ranjeva, Christian Barillot, Gilles Edan
BACKGROUND: Identifying in vivo the processes that determine lesion severity in multiple sclerosis (MS) remains a challenge. OBJECTIVES: To describe the dynamics of ultrasmall superparamagnetic iron oxide (USPIO) enhancement in MS lesions and the relationship between USPIO enhancement and microstructural changes over 3 years. METHODS: Lesion development was assessed at baseline, Months 3, 6, and 9, using magnetic resonance imaging (MRI) with gadolinium and USPIO...
October 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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