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Multiple sclerosis and iron

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https://www.readbyqxmd.com/read/29464444/cuprizone-administration-alters-the-iron-metabolism-in-the-mouse-model-of-multiple-sclerosis
#1
E Varga, E Pandur, H Abrahám, A Horváth, P Ács, S Komoly, A Miseta, K Sipos
Cuprizone (CZ) is a widely used copper chelating agent to develop non-autoimmune animal model of multiple sclerosis, characterized by demyelination of the corpus callosum (CC) and other brain regions. The exact mechanisms of CZ action are still arguable, but it seems that the only affected cells are the mature oligodendrocytes, possibly via metabolic disturbances caused by copper deficiency. During the pathogenesis of multiple sclerosis, high amount of deposited iron can be found throughout the demyelinated areas of the brain in the form of extracellular iron deposits and intracellularly accumulated iron in microglia...
February 20, 2018: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/29457657/semaphorin4a-and-h-ferritin-utilize-tim-1-on-human-oligodendrocytes-a-novel-neuro-immune-axis
#2
Brian Chiou, Elisabeth Lucassen, Michael Sather, Asha Kallianpur, James Connor
Deficiency of trophic factors relating to the survival of oligodendrocytes, combined with direct interactions with the immune system, are favored paradigms that are increasingly implicated in demyelinating diseases of the central nervous system. We and others have previously shown that Sema4A and H-ferritin interact through the T-cell immunoglobulin and mucin domain (Tim-2) receptor in mice. H-ferritin has been identified as the iron delivery protein for oligodendrocytes, whereas Sema4A causes a direct cytotoxic effect...
February 19, 2018: Glia
https://www.readbyqxmd.com/read/29439122/iron-insensitive-quantitative-assessment-of-subcortical-gray-matter-demyelination-in-multiple-sclerosis-using-the-macromolecular-proton-fraction
#3
V L Yarnykh, E P Krutenkova, G Aitmagambetova, P Repovic, A Mayadev, P Qian, L K Jung Henson, B Gangadharan, J D Bowen
BACKGROUND AND PURPOSE: Fast macromolecular proton fraction mapping is a recent quantitative MR imaging method for myelin assessment. The objectives of this study were to evaluate the macromolecular proton fraction as a measure of demyelination in subcortical GM structures in multiple sclerosis and assess a potential relationship between demyelination and excess iron deposition using the macromolecular proton fraction and T2* mapping. MATERIALS AND METHODS: Macromolecular proton fraction and T2* maps were obtained from 12 healthy controls, 18 patients with relapsing-remitting MS, and 12 patients with secondary-progressive MS using 3T MR imaging...
February 8, 2018: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/29396631/fractional-anisotropy-of-white-matter-disability-and-blood-iron-parameters-in-multiple-sclerosis
#4
Estelle Herbert, Penelope Engel-Hills, Coenraad Hattingh, Jean-Paul Fouche, Martin Kidd, Christine Lochner, Maritha J Kotze, Susan J van Rensburg
Multiple sclerosis (MS) is a disorder related to myelin damage, which can be investigated by neuroimaging techniques such as fractional anisotropy (FA), a measure of microstructural white matter properties. The objectives of this study were to investigate (1) the relationship between FA and disability using an extremes of outcome approach, and (2) whether blood iron parameters were associated with FA and/or disability. Patients diagnosed with MS (n = 107; 14 males and 93 females) had iron parameter tests and disability determinations using the Expanded Disability Status Scale (EDSS)...
February 2, 2018: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29371258/quantitative-susceptibility-mapping-of-the-thalamus-relationships-with-thalamic-volume-total-gray-matter-volume-and-t2-lesion-burden
#5
G C Chiang, J Hu, E Morris, Y Wang, S A Gauthier
BACKGROUND AND PURPOSE: Both thalamic iron deposition and atrophy have been reported in patients with multiple sclerosis compared with healthy controls, but how they are related is unclear. The purpose of this study was to understand the pathophysiologic basis for this iron deposition. MATERIALS AND METHODS: Ninety-five patients with relapsing-remitting multiple sclerosis underwent 3T MR imaging with a standardized protocol that included quantitative susceptibility mapping to measure iron concentration and a 3D T1 echo-spoiled gradient-echo sequence to obtain thalamic volumes...
January 25, 2018: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/29318974/-understanding-the-role-of-hypoxia-inducible-factor-during-neurodegeneration-for-new-therapeutics-opportunities
#6
Amalia Merelli, Julio Cesar Garcia Rodriguez, Jaume Folch, Marcelo R Regueiro, Antoni Camins, Lazarowski Alberto
Neurodegeneration (NDG) is linked with the progressive loss of neural function with intellectual and/or motor impairment. Several diseases affecting older individuals, including Alzheimer's disease, Amyotrophic Lateral Sclerosis, Huntington's disease, Parkinson's disease, stroke, Multiple Sclerosis and many others, are the most relevant disorders associated with NDG. Since other pathologies such as refractory epilepsy, brain infections, or hereditary diseases such as "neurodegeneration with brain iron accumulation", also lead to chronic brain inflammation with loss of neural cells, NDG can be said to affect all ages...
January 10, 2018: Current Neuropharmacology
https://www.readbyqxmd.com/read/29299614/cortical-and-subcortical-morphometric-and-iron-changes-in-relapsing-remitting-multiple-sclerosis-and-their-association-with-white-matter-t2%C3%A2-lesion-load-a%C3%A2-3-tesla-magnetic-resonance-imaging-study
#7
Ali Al-Radaideh, Imad Athamneh, Hadeel Alabadi, Majed Hbahbih
INTRODUCTION: This study was carried out to investigate the global and regional morphometric and iron changes in grey matter (GM) of multiple sclerosis (MS) patients and link them to the white matter (WM) lesions in a multimodal magnetic resonance imaging approach. MATERIAL AND METHODS: The study involved 30 relapsing-remitting MS (RRMS) patients along with 30 age-matched healthy controls (HC) who were scanned on a 3T Siemens Trio system. The scanning protocol included a 3D, high resolution T1, T2, and T2*-weighted sequences...
January 3, 2018: Clinical Neuroradiology
https://www.readbyqxmd.com/read/29259169/systematic-screening-of-generic-drugs-for-progressive-multiple-sclerosis-identifies-clomipramine-as-a-promising-therapeutic
#8
Simon Faissner, Manoj Mishra, Deepak K Kaushik, Jianxiong Wang, Yan Fan, Claudia Silva, Gail Rauw, Luanne Metz, Marcus Koch, V Wee Yong
The treatment of progressive multiple sclerosis (MS) is unsatisfactory. One reason is that the drivers of disease, which include iron-mediated neurotoxicity, lymphocyte activity, and oxidative stress, are not simultaneously targeted. Here we present a systematic screen to identify generic, orally available medications that target features of progressive MS. Of 249 medications that cross the blood-brain barrier, 35 prevent iron-mediated neurotoxicity in culture. Of these, several antipsychotics and antidepressants strongly reduce T-cell proliferation and oxidative stress...
December 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29205982/spasticity-or-periodic-limb-movements
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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...
December 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28966637/metabolic-pathways-as-possible-therapeutic-targets-for-progressive-multiple-sclerosis
#17
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
#18
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
#19
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
#20
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
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