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Multiple sclerosis and iron

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https://www.readbyqxmd.com/read/28430292/failure-of-the-vascular-hypothesis-of-multiple-sclerosis-in-a-rat-model-of-chronic-cerebrospinal-venous-insufficiency
#1
Maha M A Zakaria, Shahira Y Mikhael, Azza K Abu Hussein, Rania A Salah El-Din, Hany W Abd El-Malak, Iman H Hewedi, Hany S Nadim
<i>Chronic cerebrospinal venous insufficiency (CCSVI) is a series of stenotic malformations in the cerebrospinal venous outflow routes, which is postulated to cause multiple sclerosis (MS). The hypotheses assumed that CCSVI leads to iron deposition which triggers inflammation and demyelination in MS. Invasive endovascular treatment of CCSVI was initiated based on the previous theory. The present study was designed to validate this hypothesis using a rat model of CCSVI. Bilateral jugular vein ligation (JVL) was performed on female albino rats (n = 15), and sham-operated rats (n = 15) were used as a control group...
2017: Folia Neuropathologica
https://www.readbyqxmd.com/read/28408633/heterogeneity-of-cortical-lesion-susceptibility-mapping-in-multiple-sclerosis
#2
M Castellaro, R Magliozzi, A Palombit, M Pitteri, E Silvestri, V Camera, S Montemezzi, F B Pizzini, A Bertoldo, R Reynolds, S Monaco, M Calabrese
BACKGROUND AND PURPOSE: Quantitative susceptibility mapping has been used to characterize iron and myelin content in the deep gray matter of patients with multiple sclerosis. Our aim was to characterize the susceptibility mapping of cortical lesions in patients with MS and compare it with neuropathologic observations. MATERIALS AND METHODS: The pattern of microglial activation was studied in postmortem brain tissues from 16 patients with secondary-progressive MS and 5 age-matched controls...
April 13, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28391790/iron-mapping-in-multiple-sclerosis
#3
REVIEW
Stefan Ropele, Christian Enzinger, Franz Fazekas
Increased iron deposition in cerebral deep gray matter has been considered a global marker for neurodegeneration in multiple sclerosis (MS); it scales with disease duration and severity. Iron accumulation in white matter and MS lesions might be more directly related to disease activity and has been discussed as a contributor to the inflammatory and neurodegenerative cascade. New insights into iron and MS are expected from MR imaging. We discuss findings from MR iron mapping proposed. Because of the confounding magnetic properties of myelin, iron mapping in white matter remains an unresolved issue...
May 2017: Neuroimaging Clinics of North America
https://www.readbyqxmd.com/read/28351895/magnetic-poly-2-hydroxyethyl-methacrylate-microspheres-for-affinity-purification-of-antibodies-for-early-diagnosis-of-multiple-sclerosis-patients
#4
Daniel Horak, Helena Hlidkova, Yurii Kit, Rostyslav Stoika, Volodymyr Antonyuk, Severyn Myronovsky
The aim of this work is to develop new magnetic polymer microspheres with functional groups available for easy protein and antibody binding. Monodisperse macroporous poly(2-hydroxyethyl methacrylate) (PHEMA-COOH) microspheres ca. 4 µm in diameter and containing ~ 1 mmol COOH/g were synthesized by multistep swelling polymerization of 2-hydroxyethyl methacrylate (HEMA), ethylene dimethacrylate (EDMA), and [(methoxycarbonyl)methoxy]ethyl methacrylate (MCMEMA), which was followed by MCMEMA hydrolysis. The microspheres were rendered magnetic by precipitation of iron oxide inside the pores, which made them easily separable in a magnetic field...
March 28, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28332093/pathogenic-implications-of-distinct-patterns-of-iron-and-zinc-in-chronic-ms-lesions
#5
Bogdan F Popescu, Josa M Frischer, Samuel M Webb, Mylyne Tham, Reginald C Adiele, Christopher A Robinson, Patrick D Fitz-Gibbon, Stephen D Weigand, Imke Metz, Susan Nehzati, Graham N George, Ingrid J Pickering, Wolfgang Brück, Simon Hametner, Hans Lassmann, Joseph E Parisi, Guo Yong, Claudia F Lucchinetti
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) in which oligodendrocytes, the CNS cells that stain most robustly for iron and myelin are the targets of injury. Metals are essential for normal CNS functioning, and metal imbalances have been linked to demyelination and neurodegeneration. Using a multidisciplinary approach involving synchrotron techniques, iron histochemistry and immunohistochemistry, we compared the distribution and quantification of iron and zinc in MS lesions to the surrounding normal appearing and periplaque white matter, and assessed the involvement of these metals in MS lesion pathogenesis...
March 22, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28301067/progressive-iron-accumulation-across-multiple-sclerosis-phenotypes-revealed-by-sparse-classification-of-deep-gray-matter
#6
Ahmed M Elkady, Dana Cobzas, Hongfu Sun, Gregg Blevins, Alan H Wilman
PURPOSE: To create an automated framework for localized analysis of deep gray matter (DGM) iron accumulation and demyelination using sparse classification by combining quantitative susceptibility (QS) and transverse relaxation rate (R2*) maps, for evaluation of DGM in multiple sclerosis (MS) phenotypes relative to healthy controls. MATERIALS AND METHODS: R2*/QS maps were computed using a 4.7T 10-echo gradient echo acquisition from 16 clinically isolated syndrome (CIS), 41 relapsing-remitting (RR), 40 secondary-progressive (SP), 13 primary-progressive (PP) MS patients, and 75 controls...
March 16, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28283108/higher-prevalence-of-restless-legs-syndrome-willis-ekbom-disease-in-multiple-sclerosis-patients-is-related-to-spinal-cord-lesions
#7
M Minár, D Petrleničová, P Valkovič
BACKGROUND: Multiple sclerosis (MS) is connected with higher prevalence of secondary restless legs syndrome/Willis-Ekbom disease (RLS/WED). Aim of this study was to determine risk factor for developing symptoms of RLS in MS patients. METHODS: In cross-sectional study we examined 200 random MS patients. After obtaining informed consents, patients undervent a structured interview based on RLS and MS symptoms and characteristics, demographic, and health-related data...
February 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28281140/human-predisposition-to-cognitive-impairment-and-its-relation-with-environmental-exposure-to-potentially-toxic-elements
#8
Marina M S Cabral Pinto, A Paula Marinho-Reis, Agostinho Almeida, Carlos M Ordens, Maria M V G Silva, Sandra Freitas, Mário R Simões, Paula I Moreira, Pedro A Dinis, M Luísa Diniz, Eduardo A Ferreira da Silva, M Teresa Condesso de Melo
New lines of evidence suggest that less than 10% of neurodegenerative diseases have a strict genetic aetiology and other factors may be prevalent. Environmental exposures to potentially toxic elements appear to be a risk factor for Parkinson's, Alzheimer's and sclerosis diseases. This study proposes a multidisciplinary approach combining neurosciences, psychology and environmental sciences while integrating socio-economic, neuropsychological, environmental and health data. We present the preliminary results of a neuropsychological assessment carried out in elderly residents of the industrial city of Estarreja...
March 9, 2017: Environmental Geochemistry and Health
https://www.readbyqxmd.com/read/28152396/insulin-resistance-atherogenicity-and-iron-metabolism-in-multiple-sclerosis-with-and-without-depression-associations-with-inflammatory-and-oxidative-stress-biomarkers-and-uric-acid
#9
Sayonara Rangel Oliveira, Ana Paula Kallaur, Josiane Lopes, Andrea Name Colado Simão, Edna Maria Vissoci Reiche, Elaine Regina Delicato de Almeida, Helena Kaminami Morimoto, Wildea Lice de Carvalho Jennings de Pereira, Daniela Frizon Alfieri, Tamires Flauzino, Caio de Meleck Proença, Anna Maria Gomes, Damacio Ramón Kaimen-Maciel, Michael Maes
Depression is accompanied by metabolic disorders in iron metabolism, lipoproteins, and insulin resistance. We measured plasma levels of ferritin, iron, lipids, insulin, and glucose and computed the homeostasis model assessment (HOMA2IR) and atherogenic index of plasma (AIP) in MS patients with and without depression and healthy controls. Explanatory variables were serum uric acid, interleukin (IL)-6, lipid hydroperoxides (CL-LOOH), albumin, and C-reactive protein (CRP). Depression was assessed using the Hospital Anxiety and Depression Scale (HADS), neurological disability using the Expanded Disability Status Scale (EDSS), and disease progression using ∆EDSS over five years earlier...
April 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28147220/intersections-of-pathways-involving-biotin-and-iron-relative-to-therapeutic-mechanisms-for-progressive-multiple-sclerosis
#10
Rebecca M Heidker, Mitchell R Emerson, Steven M LeVine
While there are a variety of therapies for relapsing remitting multiple sclerosis (MS), there is a lack of treatments for progressive MS. An early study indicated that high dose biotin therapy has beneficial effects in approximately 12-15% of patients with progressive MS. The mechanisms behind the putative improvements seen with biotin therapy are not well understood, but have been postulated to include: 1) improving mitochondrial function which is impaired in MS, 2) increasing synthesis of lipids and cholesterol to facilitate remyelination, and 3) affecting gene expression...
December 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28038965/inversion-recovery-ultrashort-echo-time-magnetic-resonance-imaging-a-method-for-simultaneous-direct-detection-of-myelin-and-high-signal-demonstration-of-iron-deposition-in-the-brain-a-feasibility-study
#11
Vipul R Sheth, Shujuan Fan, Qun He, Yajun Ma, Jacopo Annese, Robert Switzer, Jody Corey-Bloom, Graeme M Bydder, Jiang Du
Multiple sclerosis (MS) causes demyelinating lesions in the white matter and increased iron deposition in the subcortical gray matter. Myelin protons have an extremely short T2* (<1ms) and are not directly detected with conventional clinical magnetic resonance (MR) imaging sequences. Iron deposition also reduces T2*, leading to reduced signal on clinical sequences. In this study we tested the hypothesis that the inversion recovery ultrashort echo time (IR-UTE) pulse sequence can directly and simultaneously image myelin and iron deposition using a clinical 3T scanner...
December 28, 2016: Magnetic Resonance Imaging
https://www.readbyqxmd.com/read/28007423/rgms-structural-insights-molecular-regulation-and-downstream-signaling
#12
REVIEW
Christian Siebold, Toshihide Yamashita, Philippe P Monnier, Bernhard K Mueller, R Jeroen Pasterkamp
Although originally discovered as neuronal growth cone-collapsing factors, repulsive guidance molecules (RGMs) are now known as key players in many fundamental processes, such as cell migration, differentiation, iron homeostasis, and apoptosis, during the development and homeostasis of many tissues and organs, including the nervous, skeletal, and immune systems. Furthermore, three RGMs (RGMa, RGMb/DRAGON, and RGMc/hemojuvelin) have been linked to the pathogenesis of various disorders ranging from multiple sclerosis (MS) to cancer and juvenile hemochromatosis (JHH)...
May 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/27996064/free-serum-haemoglobin-is-associated-with-brain-atrophy-in-secondary-progressive-multiple-sclerosis
#13
Alex Lewin, Shea Hamilton, Aviva Witkover, Paul Langford, Richard Nicholas, Jeremy Chataway, Charles R M Bangham
Background A major cause of disability in secondary progressive multiple sclerosis (SPMS) is progressive brain atrophy, whose pathogenesis is not fully understood. The objective of this study was to identify protein biomarkers of brain atrophy in SPMS. Methods We used surface-enhanced laser desorption-ionization time-of-flight mass spectrometry to carry out an unbiased search for serum proteins whose concentration correlated with the rate of brain atrophy, measured by serial MRI scans over a 2-year period in a well-characterized cohort of 140 patients with SPMS...
November 15, 2016: Wellcome Open Research
https://www.readbyqxmd.com/read/27906525/the-clinical-utility-of-qsm-disease-diagnosis-medical-management-and-surgical-planning
#14
REVIEW
Sarah Eskreis-Winkler, Yan Zhang, Jingwei Zhang, Zhe Liu, Alexey Dimov, Ajay Gupta, Yi Wang
Quantitative susceptibility mapping (QSM) is an MR technique that depicts and quantifies magnetic susceptibility sources. Mapping iron, the dominant susceptibility source in the brain, has many important clinical applications. Herein, we review QSM applications in the diagnosis, medical management, and surgical treatment of disease. To assist in early disease diagnosis, QSM can identify elevated iron levels in the motor cortex of amyotrophic lateral sclerosis patients, in the substantia nigra of Parkinson's disease (PD) patients, in the globus pallidus, putamen, and caudate of Huntington's disease patients, and in the basal ganglia of Wilson's disease patients...
December 1, 2016: NMR in Biomedicine
https://www.readbyqxmd.com/read/27851995/key-clinical-benefits-of-neuroimaging-at-7t
#15
Siegfried Trattnig, Elisabeth Springer, Wolfgang Bogner, Gilbert Hangel, Bernhard Strasser, Barbara Dymerska, Pedro Lima Cardoso, Simon Daniel Robinson
The growing interest in ultra-high field MRI, with more than 35.000 MR examinations already performed at 7T, is related to improved clinical results with regard to morphological as well as functional and metabolic capabilities. Since the signal-to-noise ratio increases with the field strength of the MR scanner, the most evident application at 7T is to gain higher spatial resolution in the brain compared to 3T. Of specific clinical interest for neuro applications is the cerebral cortex at 7T, for the detection of changes in cortical structure, like the visualization of cortical microinfarcts and cortical plaques in Multiple Sclerosis...
November 13, 2016: NeuroImage
https://www.readbyqxmd.com/read/27829982/new-insights-into-the-role-of-oxidative-stress-mechanisms-in-the-pathophysiology-and-treatment-of-multiple-sclerosis
#16
REVIEW
Bożena Adamczyk, Monika Adamczyk-Sowa
Multiple sclerosis (MS) is a multifactorial disease of the central nervous system (CNS) characterized by an inflammatory process and demyelination. The etiology of the disease is still not fully understood. Therefore, finding new etiological factors is of such crucial importance. It is suspected that the development of MS may be affected by oxidative stress (OS). In the acute phase OS initiates inflammatory processes and in the chronic phase it sustains neurodegeneration. Redox processes in MS are associated with mitochondrial dysfunction, dysregulation of axonal bioenergetics, iron accumulation in the brain, impaired oxidant/antioxidant balance, and OS memory...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27808258/significant-glial-alterations-in-response-to-iron-loading-in-a-novel-organotypic-hippocampal-slice-culture-model
#17
Sinead Healy, Jill McMahon, Peter Owens, Una FitzGerald
Aberrant iron deposition in the brain is associated with neurodegenerative disorders including Multiple Sclerosis, Alzheimer's disease and Parkinson's disease. To study the collective response to iron loading, we have used hippocampal organotypic slices as a platform to develop a novel ex vivo model of iron accumulation. We demonstrated differential uptake and toxicity of iron after 12 h exposure to 10 μM ferrous ammonium sulphate, ferric citrate or ferrocene. Having established the supremacy of ferrocene in this model, the cultures were then loaded with 0...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27799546/in-vivo-nanoparticle-imaging-of-innate-immune-cells-can-serve-as-a-marker-of-disease-severity-in-a-model-of-multiple-sclerosis
#18
Klara Kirschbaum, Jana K Sonner, Matthias W Zeller, Katrin Deumelandt, Julia Bode, Rakesh Sharma, Thomas Krüwel, Manuel Fischer, Angelika Hoffmann, Milene Costa da Silva, Martina U Muckenthaler, Wolfgang Wick, Björn Tews, John W Chen, Sabine Heiland, Martin Bendszus, Michael Platten, Michael O Breckwoldt
Innate immune cells play a key role in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Current clinical imaging is restricted to visualizing secondary effects of inflammation, such as gliosis and blood-brain barrier disruption. Advanced molecular imaging, such as iron oxide nanoparticle imaging, can allow direct imaging of cellular and molecular activity, but the exact cell types that phagocytose nanoparticles in vivo and how phagocytic activity relates to disease severity is not well understood...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27796537/slow-expansion-of-multiple-sclerosis-iron-rim-lesions-pathology-and-7%C3%A2-t-magnetic-resonance-imaging
#19
Assunta Dal-Bianco, Günther Grabner, Claudia Kronnerwetter, Michael Weber, Romana Höftberger, Thomas Berger, Eduard Auff, Fritz Leutmezer, Siegfried Trattnig, Hans Lassmann, Francesca Bagnato, Simon Hametner
In multiple sclerosis (MS), iron accumulates inside activated microglia/macrophages at edges of some chronic demyelinated lesions, forming rims. In susceptibility-based magnetic resonance imaging at 7 T, iron-laden microglia/macrophages induce a rim of decreased signal at lesion edges and have been associated with slowly expanding lesions. We aimed to determine (1) what lesion types and stages are associated with iron accumulation at their edges, (2) what cells at the lesion edges accumulate iron and what is their activation status, (3) how reliably can iron accumulation at the lesion edge be detected by 7 T magnetic resonance imaging (MRI), and (4) if lesions with rims enlarge over time in vivo, when compared to lesions without rims...
January 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/27746629/the-brain-proteome-of-the-ubiquitin-ligase-peli1-knock-out-mouse-during-experimental-autoimmune-encephalomyelitis
#20
Ragnhild Reehorst Lereim, Eystein Oveland, Yichuan Xiao, Øivind Torkildsen, Stig Wergeland, Kjell-Morten Myhr, Shao-Cong Sun, Frode S Berven
The ubiquitin ligase Peli1 has previously been suggested as a potential treatment target in multiple sclerosis. In the multiple sclerosis disease model, experimental autoimmune encephalomyelitis, Peli1 knock-out led to less activated microglia and less inflammation in the central nervous system. Despite being important in microglia, Peli1 expression has also been detected in glial and neuronal cells. In the present study the overall brain proteomes of Peli1 knock-out mice and wild-type mice were compared prior to experimental autoimmune encephalomyelitis induction, at onset of the disease and at disease peak...
September 2016: Journal of Proteomics & Bioinformatics
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