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Multiple sclerosis and iron

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
Rachel Waller, M Nicola Woodroofe, Stephen B Wharton, Paul G Ince, Simona Francese, Paul R Heath, Alex Cudzich-Madry, Ruth H Thomas, Natalie Rounding, Basil Sharrack, Julie E Simpson
Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS). White matter lesions in MS are surrounded by areas of non-demyelinated normal appearing white matter (NAWM) with complex pathology, including blood brain barrier dysfunction, axonal damage and glial activation. Astrocytes, the most abundant cell type within the CNS, may respond and/or contribute to lesion pathogenesis. We aimed to characterise the transcriptomic profile of astrocytes in NAWM to determine whether specific glial changes exist in the NAWM which contribute to lesion development or prevent disease progression...
October 15, 2016: Journal of Neuroimmunology
Božena Ćurko-Cofek, Tanja Grubić Kezele, Jelena Marinić, Marin Tota, Nada Starčević Čizmarević, Čedomila Milin, Smiljana Ristić, Biserka Radošević-Stašić, Vesna Barac-Latas
To analyze iron- and gender-dependent mechanisms possibly involved in pathogenesis of multiple sclerosis (MS) in this study we evaluated the effects of iron overload (IO) on iron status and lipid peroxidation processes (LPO) in tissues of female and male DA rats during chronic relapsing experimental autoimmune encephalomyelitis, a well-established MS animal model. Rats were treated by iron sucrose (75mg/kg bw/day) or with saline solution during two weeks before the sensitization with bovine brain homogenate in complete Freund's adjuvant...
August 26, 2016: Neurotoxicology
Moones Heidari, Sam H Gerami, Brianna Bassett, Ross M Graham, Anita C G Chua, Ritambhara Aryal, Michael J House, Joanna F Collingwood, Conceição Bettencourt, Henry Houlden, Mina Ryten, John K Olynyk, Debbie Trinder, Daniel M Johnstone, Elizabeth A Milward
We previously demonstrated elevated brain iron levels in myelinated structures and associated cells in a hemochromatosis Hfe (-/-) xTfr2 (mut) mouse model. This was accompanied by altered expression of a group of myelin-related genes, including a suite of genes causatively linked to the rare disease family 'neurodegeneration with brain iron accumulation' (NBIA). Expanded data mining and ontological analyses have now identified additional myelin-related transcriptome changes in response to brain iron loading...
2016: Rare Diseases
Thomas Gattringer, Michael Khalil, Christian Langkammer, Margit Jehna, Alexander Pichler, Daniela Pinter, Markus Kneihsl, Katja Petrovic, Stefan Ropele, Franz Fazekas, Christian Enzinger
Besides specific iron accumulation in some neurodegenerative disorders, increased iron deposition in cerebral deep gray matter (DGM) is found in multiple sclerosis. As this is considered largely a white matter (WM) disease, we speculated that patients with more severe ischemic WM hyperintensities (WMH) might also have an increased iron concentration in DGM structures and tested this assumption by using magnetic resonance imaging-based quantitative R2* relaxometry. WMH severity was measured in 61 patients with acute transient neurological symptoms (mean age: 71...
September 2016: Neurobiology of Aging
C Veauthier, F Paul
BACKGROUND: Fatigue is one of the most frequent symptoms of multiple sclerosis (MS) and one of the main reasons for underemployment and early retirement. The mechanisms of MS-related fatigue are unknown but comorbid disorders play a major role. Anemia, diabetes, side effects of medication and depression should be ruled out. Moreover, excessive daytime sleepiness (EDS) should be differentiated from fatigue. No approved medicinal therapy of MS fatigue is currently available. OBJECTIVE: Presentation of current treatment strategies with a particular focus on secondary fatigue due to sleep disorders...
July 21, 2016: Der Nervenarzt
Massimo Filippi, Paolo Preziosa, Maria A Rocca
Due to its sensitivity to the different multiple sclerosis (MS)-related abnormalities, magnetic resonance imaging (MRI) has become an established tool to diagnose MS and to monitor its evolution. MRI has been included in the diagnostic workup of patients with clinically isolated syndromes suggestive of MS, and ad hoc criteria have been proposed and are regularly updated. In patients with definite MS, the ability of conventional MRI techniques to explain patients' clinical status and progression of disability is still suboptimal...
2016: Handbook of Clinical Neurology
Monika Adamczyk-Sowa, Paweł Sowa, Sebastian Mucha, Jacek Zostawa, Bogdan Mazur, Maciej Owczarek, Krystyna Pierzchała
BACKGROUND The cause of multiple sclerosis (MS) is currently unknown, but it is thought that oxidative damage and iron metabolism mechanisms are involved. The aim of this study was to examine ceruloplasmin concentration in MS patients based on various immunomodifying therapies and to test the effect of antioxidative melatonin on ceruloplasmin levels. MATERIAL AND METHODS This prospective study included 102 MS patients and 15 healthy controls. Patients were divided into groups according to different immunomodifying therapies: interferons beta 1a, interferons beta 1b, glatiramer acetate, mitoxantrone, and immunomodifying pre-treatment (A, B, G, Mx, and P groups, respectively), and the relapse R group...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
M A Greenough, A Ramírez Munoz, A I Bush, C M Opazo
Copper is an essential metal ion that provides catalytic function to numerous enzymes and also regulates neurotransmission and intracellular signaling. Conversely, a deficiency or excess of copper can cause chronic disease in humans. Menkes and Wilson disease are two rare heritable disorders of copper transport that are characterized by copper deficiency and copper overload, respectively. Changes to copper status are also a common feature of several neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS)...
September 1, 2016: Metallomics: Integrated Biometal Science
W Bian, E Tranvinh, T Tourdias, M Han, T Liu, Y Wang, B Rutt, M M Zeineh
BACKGROUND AND PURPOSE: Magnetic susceptibility measured with quantitative susceptibility mapping has been proposed as a biomarker for demyelination and inflammation in patients with MS, but investigations have mostly been on white matter lesions. A detailed characterization of cortical lesions has not been performed. The purpose of this study was to evaluate magnetic susceptibility in both cortical and WM lesions in MS by using quantitative susceptibility mapping. MATERIALS AND METHODS: Fourteen patients with MS were scanned on a 7T MR imaging scanner with T1-, T2-, and T2*-weighted sequences...
June 9, 2016: AJNR. American Journal of Neuroradiology
Martina Absinta, Pascal Sati, Matthew Schindler, Emily C Leibovitch, Joan Ohayon, Tianxia Wu, Alessandro Meani, Massimo Filippi, Steven Jacobson, Irene C M Cortese, Daniel S Reich
BACKGROUND: In some active multiple sclerosis (MS) lesions, a strong immune reaction at the lesion edge may contain growth and thereby isolate the lesion from the surrounding parenchyma. Our previous studies suggest that this process involves opening of the blood-brain barrier in capillaries at the lesion edge, seen on MRI as centripetal contrast enhancement and a colocalized phase rim. We hypothesized that using these features to characterize early lesion evolution will allow in vivo tracking of tissue degeneration and/or repair, thus improving the evaluation of potential therapies for chronic active lesions...
July 1, 2016: Journal of Clinical Investigation
Y Zhang, S A Gauthier, A Gupta, W Chen, J Comunale, G C-Y Chiang, D Zhou, G Askin, W Zhu, D Pitt, Y Wang
BACKGROUND AND PURPOSE: Quantitative susceptibility mapping and R2* are sensitive to myelin and iron changes in multiple sclerosis lesions. This study was designed to characterize lesion changes on quantitative susceptibility mapping and R2* at various gadolinium-enhancement stages. MATERIALS AND METHODS: This study included 64 patients with MS with different enhancing patterns in white matter lesions: nodular, shell-like, nonenhancing < 1 year old, and nonenhancing 1-3 years old...
September 2016: AJNR. American Journal of Neuroradiology
Jiasi Li, Lei Zhang, Yongxin Chu, Michael Namaka, Benqiang Deng, Jiming Kong, Xiaoying Bi
White matter is primarily composed of myelin and myelinated axons. Structural and functional completeness of myelin is critical for the reliable and efficient transmission of information. White matter injury has been associated with the development of many demyelinating diseases. Despite a variety of scientific advances aimed at promoting re-myelination, their benefit has proven at best to be marginal. Research suggests that the failure of the re-myelination process may be the result of an unfavorable microenvironment...
2016: Frontiers in Cellular Neuroscience
Niels Bergsland, Eleonora Tavazzi, Maria Marcella Laganà, Francesca Baglio, Pietro Cecconi, Stefano Viotti, Robert Zivadinov, Giuseppe Baselli, Marco Rovaris
BACKGROUND AND PURPOSE: With respect to healthy controls (HCs), increased iron concentrations in the deep gray matter (GM) and decreased white matter (WM) integrity are common findings in multiple sclerosis (MS) patients. The association between these features of the disease remains poorly understood. We investigated the relationship between deep iron deposition in the deep GM and WM injury in associated fiber tracts in MS patients. METHODS: Sixty-six MS patients (mean age 50...
May 30, 2016: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
Meric A Altinoz, Emin M Ozcan, Bahri Ince, Sinan Guloksuz
Basic science investigations and clinical observations in recent years indicate that hemoglobins (Hbs) may have important roles in the pathogenesis of multiple sclerosis (MS). These findings can be summarized as follows: 1- Erythrocyte fragility is higher in MS patients, the released free Hb damages blood-brain barrier, myelin basic protein and also triggers iron overload and inflammation. 2- Free Hb may further activate the inflammatory responses through Toll-like receptor 4 (TLR4), present on microglia and other innate immunocytes...
October 2016: Metabolic Brain Disease
Antonio Giorgio, Nicola De Stefano
Conventional magnetic resonance imaging (MRI) of the central nervous system is crucial for an early and reliable diagnosis and monitoring of patients with multiple sclerosis (MS). Focal white matter (WM) lesions, as detected by MRI, are the pathological hallmark of the disease and show some relation to clinical disability, especially in the long run. Gray matter (GM) involvement is evident from disease onset and includes focal (i.e., cortical lesions) and diffuse pathology (i.e., atrophy). Both accumulate over time and show close relation to physical disability and cognitive impairment...
April 2016: Seminars in Neurology
Tatiana Claro da Silva, Christian Hiller, Zhibo Gai, Gerd A Kullak-Ublick
Vitamin D3 regulates genes critical for human health and its deficiency is associated with an increased risk for osteoporosis, cancer, diabetes, multiple sclerosis, hypertension, inflammatory and immunological diseases. To study the impact of vitamin D3 on genes relevant for the transport and metabolism of nutrients and drugs, we employed next-generation sequencing (NGS) and analyzed global gene expression of the human-derived Caco-2 cell line treated with 500nM vitamin D3. Genes involved in neuropeptide signaling, inflammation, cell adhesion and morphogenesis were differentially expressed...
October 2016: Journal of Steroid Biochemistry and Molecular Biology
Marloes Hagens, Bart van Berckel, Frederik Barkhof
PURPOSE OF REVIEW: Gadolinium-enhancement depicts blood-brain barrier disruption associated with new inflammatory MRI lesions in multiple sclerosis (MS) and is widely used for diagnosis and therapeutic monitoring. However, earlier and more specific markers of inflammation are urgently needed. RECENT FINDINGS: Susceptibility-weighted images demonstrate the importance of the central vein in the formation of MS lesions. Perfusion weighted imaging techniques can show focal and diffuse low-grade inflammatory changes not visible on conventional MRI...
June 2016: Current Opinion in Neurology
Petr Dusek, Susanne A Schneider, Jan Aaseth
Disturbance of cerebral iron regulation is almost universal in neurodegenerative disorders. There is a growing body of evidence that increased iron deposits may contribute to degenerative changes. Thus, the effect of iron chelation therapy has been investigated in many neurological disorders including rare genetic syndromes with neurodegeneration with brain iron accumulation as well as common sporadic disorders such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis. This review summarizes recent advances in understanding the role of iron in the etiology of neurodegeneration...
December 2016: Journal of Trace Elements in Medicine and Biology
S Chawla, I Kister, J Wuerfel, J-C Brisset, S Liu, T Sinnecker, P Dusek, E M Haacke, F Paul, Y Ge
BACKGROUND AND PURPOSE: Characterization of iron deposition associated with demyelinating lesions of multiple sclerosis and neuromyelitis optica has not been well studied. Our aim was to investigate the potential of ultra-high-field MR imaging to distinguish MS from neuromyelitis optica and to characterize tissue injury associated with iron pathology within lesions. MATERIALS AND METHODS: Twenty-one patients with MS and 21 patients with neuromyelitis optica underwent 7T high-resolution 2D-gradient-echo-T2* and 3D-susceptibility-weighted imaging...
July 2016: AJNR. American Journal of Neuroradiology
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