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Demyelination diseases

Dylan A Galloway, Stephanie N Blandford, Tangyne Berry, John B Williams, Mark Stefanelli, Michelle Ploughman, Craig S Moore
In the injured central nervous system, myeloid cells, including macrophages and microglia, are key contributors to both myelin injury and repair. This immense plasticity emphasizes the need to further understand the precise molecular mechanisms that contribute to the dynamic regulation of myeloid cell polarization and function. Herein, we demonstrate that miR-223 is upregulated in multiple sclerosis (MS) patient monocytes and the alternatively-activated and tissue-regenerating M2-polarized human macrophages and microglia...
December 11, 2018: Glia
Shivaprasad H Venkatesha, Steven Dudics, Yang Song, Anup Mahurkar, Kamal D Moudgil
Multiple sclerosis (MS) is a debilitating autoimmune disease affecting over 2.3 million people worldwide, and it is characterized by inflammation and demyelination of nerve cells. The currently available biomarkers for the diagnosis and management of MS have inherent limitations, therefore, additional new biomarkers are needed. We studied the microRNA (miRNA) profile of splenocytes of mice having experimental autoimmune encephalomyelitis (EAE), a model of human MS. A miRNA-microarray analysis revealed increased expression of nine miRNAs (let-7e, miR-23b, miR-31, miR-99b, miR-125a, miR-146b, miR-155, miR-193b, and miR-221) following EAE development...
December 11, 2018: International Journal of Molecular Sciences
Yuhe Mao, Min Zhang, Shaojun Liu, Yunyu Xu, Jun Xue, Chuanming Hao, Lingyun Lai
RATIONALE: Inflammatory demyelinating neuropathies such as Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and focal segmental glomerulosclerosis (FSGS) are autoimmune disorders that may have a common pathogenesis. Here, we describe 2 unique cases of FSGS, 1 with GBS and the other with CIPD. We believe that reviewing these multisystemic diseases will help in better understanding of FSGS pathogenesis. PATIENT CONCERNS: The 1st patient, a 66-year-old woman, complained of tingling and numbness in the limbs and within 2 days, she developed progressive muscle weakness...
December 2018: Medicine (Baltimore)
Giovanni Tangherlini, Dmitrii V Kalinin, Dirk Schepmann, Tao Che, Nadine Mykicki, Sonja Ständer, Karin Loser, Bernhard Wünsch
Neuroinflammatory disorders, such as multiple sclerosis (MS) or experimental autoimmune encephalomyelitis (EAE), an established mouse model mimicking part of the human pathology, are characterized by inflammatory infiltrates containing T helper 1 (TH1) and TH17 cells, which cause demyelination and neurodegeneration. Disease onset and perpetuation are mediated by peripherally generated autoreactiveT cells infiltrating into the central nervous system, where they are re-stimulated by antigen-presenting cells. Here, we show that newly designed peripherally active, potent and selective kappa-opioid receptor (KOR) agonists comprising the ethylenediamine KOR pharmacophore in a perhydroquinoxaline scaffold exhibit potent anti-inflammatory capacities in primary antigen presenting cells as well as T cells...
December 13, 2018: Journal of Medicinal Chemistry
Patrizia LoPresti
Central nervous system (CNS) degeneration occurs during multiple sclerosis (MS) following several years of reversible autoimmune demyelination. Progressive CNS degeneration appears later during the course of relapsing-remitting MS (RRMS), although it starts insidiously at disease onset. We propose that there is an early subclinical phase also for primary-progressive (PP) MS. Consensus exists that many different cell types are involved during disease onset. Furthermore, the response to the initial damage, which is specific for each individual, would result in distinct pathological pathways that add complexity to the disease and the mechanisms underlying progressive CNS degeneration...
2018: Frontiers in Neurology
Yi Guan, Dejan Jakimovski, Murali Ramanathan, Bianca Weinstock-Guttman, Robert Zivadinov
Multiple sclerosis (MS) is a disease of the central nervous system characterized by inflammation, demyelination, and neuronal damage. Environmental and genetic factors are associated with the risk of developing MS, but the exact cause still remains unidentified. Epstein-Barr virus (EBV), vitamin D, and smoking are among the most well-established environmental risk factors in MS. Infectious mononucleosis, which is caused by delayed primary EBV infection, increases the risk of developing MS. EBV may also contribute to MS pathogenesis indirectly by activating silent human endogenous retrovirus-W...
March 2019: Neural Regeneration Research
Hamid Zahednasab, Masoumeh Firouzi, Sussan Kaboudanian-Ardestani, Zahra Mojallal-Tabatabaei, Sajad Karampour, Hossein Keyvani
Multiple sclerosis (MS) is a disease of the central nervous system (CNS) in which both neuroinflammation and neurodegeneration play critical roles in the pathogenesis of the disease. A growing body of evidence indicates that some antibiotics have anti-inflammatory and neuroprotective properties. Rifampicin, commonly used for the treatment of mycobacteria, has been shown to exert neuroprotective activities in neurodegenerative diseases. In this study, we examined the efficacy of rifampicin on demyelination, gliosis, apoptosis, inflammation, behavioral dysfunction, and biochemical alterations in the cuprizone model of demyelination...
January 2019: Cytokine
Shuangwen Yu, Mei Liu, Kaili Hu
Multiple sclerosis is an autoimmune neurodegenerative disease, which usually caused by inflammation, demyelination, and axonal injury. The currently available medications for multiple sclerosis do not directly promote myelin sheath repair. Therefore, many researches have attempted to achieve better therapeutic effects through promoting remyelination. Natural products not only alleviate clinical symptoms, but also have the unique advantages of protecting and repairing effects on nervous system. We here present a systematic review on published papers about treating multiple sclerosis by natural products, aiming to provide comprehensive information on natural products in the treatment of multiple sclerosis...
December 8, 2018: International Immunopharmacology
Sogol Meknatkhah, Pouya Sharif Dashti, Monireh-Sadat Mousavi, Amirbahador Zeynali, Shahin Ahmadian, Saeed Karima, Ali Akbar Saboury, Gholam Hossein Riazi
Multiple sclerosis (MS) is known as the most common demyelinating disease worldwide in which previous studies have shown that stress is a risk factor for the disease's onset and progression. Nevertheless, further studies are needed to investigate the consequences of stress in MS pathology. In this study, after 5 days of exposure to psychological and physical stress as a repetitive distress modality, rats were treated with cuprizone. The demyelination degree was compared in animal groups using Luxol fast blue staining, immunohistochemical staining for myelin basic protein and transmission electron microscopy...
December 10, 2018: Neuropathology: Official Journal of the Japanese Society of Neuropathology
Gabriela Seabra, Valéria de Almeida, Daniel Martins-de-Souza
Techniques such as the maturation and differentiation of cell lines and progenitor cells are important for the improvement and development of representative and relevant in vitro models. In this context, the following chapter proposes a maturation model of the MO3.13 cell line, aiming to contribute to a more robust and credible in vitro model of human oligodendrocytes. This may prove to be an important tool in the study of diseases related to dysfunctions in oligodendrocytes and demyelination, including schizophrenia and multiple sclerosis...
2019: Methods in Molecular Biology
Laura Emilia Toader, Gabriela Camelia Roşu, Bogdan Cătălin, Ionica Pirici, Ion Cristian Gîlceavă, Valeria Carmen Albu, Anca Maria Istrate-Ofiţeru, Dafin Fior Mureşanu, Daniel Pirici
Multiple sclerosis (MS) is a complex chronic neurodegenerative disease that involves an abnormal autoimmune response directed against the brain, nerves and spinal cord; it is considered the most frequent cause of neurological disability, because MS-associated inflammatory lesions can affect a wide range of systems to a varying degree and may cause a plethora of neurological comorbidities and symptoms. The symptoms are quite variable from patient to patient and depend on the spatial distribution of the central nervous system (CNS) lesions, but usually involve sensory disturbances, cognitive deficits, unilateral vision loss, bladder dysfunction, ataxia, fatigue, double vision, weakness of the limbs and intestinal disorders...
2018: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
Netanel Karbian, Yael Eshed-Eisenbach, Adi Tabib, Hila Hoizman, B Paul Morgan, Ora Schueler-Furman, Elior Peles, Dror Mevorach
Objective: To characterize all 4 mutations described for CD59 congenital deficiency. Methods: The 4 mutations, p.Cys64Tyr, p.Asp24Val, p.Asp24Valfs*, and p.Ala16Alafs*, were described in 13 individuals with CD59 malfunction. All 13 presented with recurrent Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy, recurrent strokes, and chronic hemolysis. Here, we track the molecular consequences of the 4 mutations and their effects on CD59 expression, localization, glycosylation, degradation, secretion, and function...
December 2018: Neurology. Genetics
Hui Ye, Jeffrey Ng
Axonal stimulation with electric currents is an effective method for controlling neural activity. An electric field parallel to the axon is widely accepted as the predominant component in the activation of an axon. However, recent studies indicate that the transverse component to the axolemma is also effective in depolarizing the axon. To quantitatively investigate the amount of axolemma polarization induced by a transverse electric field, we computed the transmembrane potential ( Vm ) for a conductive body that represents an unmyelinated axon (or the bare axon between the myelin sheath in a myelinated axon)...
2018: PeerJ
Iñaki Osorio-Querejeta, Ainhoa Alberro, Maider Muñoz-Culla, Imre Mäger, David Otaegui
Multiple Sclerosis is a demyelinating disease of the central nervous system for which no remyelination therapy is available and alternative strategies are being tested. Extracellular vesicles (EVs) have emerged as players in physiological and pathological processes and are being proposed as therapeutic targets and mediators. More concretely, EVs have shown to be involved in myelination related processes such as axon-oligodendrocyte communication or oligodendrocyte precursor cell migration. In addition, EVs have been shown to carry genetic material and small compounds, and to be able to cross the Blood Brain Barrier...
2018: Frontiers in Molecular Neuroscience
Sourajit M Mustafi, Jaroslaw Harezlak, Chandana Kodiweera, Jennifer S Randolph, James C Ford, Heather A Wishart, Yu-Chien Wu
Multiple sclerosis is a neurodegenerative and inflammatory disease, a hallmark of which is demyelinating lesions in the white matter. We hypothesized that alterations in white matter microstructures can be non-invasively characterized by advanced diffusion magnetic resonance imaging. Seven diffusion metrics were extracted from hybrid diffusion imaging acquisitions via classic diffusion tensor imaging, neurite orientation dispersion and density imaging, and q-space imaging. We investigated the sensitivity of the diffusion metrics in 36 sets of regions of interest in the brain white matter of six female patients (age 52...
January 2019: Neural Regeneration Research
Maciej Juryńczyk, Anu Jacob, Kazuo Fujihara, Jacqueline Palace
The field of central nervous system (CNS) inflammatory diseases has recently broadened to include a new condition associated with pathogenic serum antibodies against myelin oligodendrocyte glycoprotein (MOG). This is distinct from multiple sclerosis (MS) and aquaporin-4 (AQP4) antibody neuromyelitis optica spectrum disorders (NMOSD). MOG antibody-associated disease phenotypes are varied and range from classical neuromyelitis optica to acute demyelinating encephalomyelitis and cortical encephalitis. The diagnosis depends on using a reliable, specific and sensitive assay of the antibody...
December 8, 2018: Practical Neurology
Enrique Gabandé-Rodríguez, Azucena Pérez-Cañamás, Beatriz Soto-Huelin, Daniel N Mitroi, Sara Sánchez-Redondo, Elena Martínez-Sáez, César Venero, Héctor Peinado, María Dolores Ledesma
Neuropathic lysosomal storage disorders (LSDs) present with activated pro-inflammatory microglia. However, anti-inflammatory treatment failed to improve disease pathology. We characterise the mechanisms underlying microglia activation in Niemann-Pick disease type A (NPA). We establish that an NPA patient and the acid sphingomyelinase knockout (ASMko) mouse model show amoeboid microglia in neurodegeneration-prone areas. In vivo microglia ablation worsens disease progression in ASMko mice. We demonstrate the coexistence of different microglia phenotypes in ASMko brains that produce cytokines or counteract neuronal death by clearing myelin debris...
December 7, 2018: EMBO Journal
Ji Zhou, Xiaopeng Lu, Yao Zhang, Taoyun Ji, Yiwen Jin, Min Xu, Xinhua Bao, Yuehua Zhang, Hui Xiong, Xingzhi Chang, Yuwu Jiang, Ye Wu
BACKGROUND: Some studies have reported clinical features of relapsing MOG-IgG-associated CNS demyelination principally in Caucasians children. It is not clear whether Chinese children share the same phenotype. OBJECTIVE: To delineate the clinical characteristics in Chinese children with relapsing MOG-IgG-associated demyelination. METHODS: A follow-up study on 23 Children with relapsing MOG-IgG-associated demyelination from two Chinese tertiary hospitals was performed...
December 3, 2018: Multiple Sclerosis and related Disorders
Atay Vural, Serhat Okar, Aslı Kurne, Güliz Sayat-Gürel, Nazire Pınar Acar, Erdem Karabulut, Kader Karlı Oğuz, Sibel Kadayıfçılar, Rana Karabudak
BACKGROUND: The extent of neurodegeneration in the earliest stages of central nervous system (CNS) demyelination is not known. Optical coherence tomography (OCT) is a powerful tool to study neurodegeneration in demyelinating disorders. OBJECTIVES: To study neuroaxonal loss in the retina of individuals with radiologically isolated syndrome (RIS) and investigate whether OCT measurements are associated with brain volumetrics and clinical conversion to multiple sclerosis (MS)...
December 11, 2018: Multiple Sclerosis: Clinical and Laboratory Research
Alberto Terrin, Federico Mainardi, Ferdinando Maggioni
BACKGROUND: The recently released International Classification of Headache Disorders-3rd edition (1) includes migraine aura status (MAS) among the complications of migraine (A1.4.5). It is defined as the recurrence of at least three auras over a period of 3 days, in a patient suffering from migraine fulfilling criteria for 1.2 Migraine with aura (MA) or one of its subtypes. CASE SERIES: We describe three cases of MAS secondary to an organic brain lesion: a migrainous infarction, an acute ischemic stroke secondary to a vertebral artery dissection, and an inflammatory demyelinating disease of the central nervous system...
December 6, 2018: Neurological Sciences
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