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https://www.readbyqxmd.com/read/29223871/intensity-ratio-to-improve-black-hole-assessment-in-multiple-sclerosis
#1
Gautam Adusumilli, Kathryn Trinkaus, Peng Sun, Samantha Lancia, Jeffrey D Viox, Jie Wen, Robert T Naismith, Anne H Cross
BACKGROUND: Improved imaging methods are critical to assess neurodegeneration and remyelination in multiple sclerosis. Chronic hypointensities observed on T1-weighted brain MRI, "persistent black holes," reflect severe focal tissue damage. Present measures consist of determining persistent black holes numbers and volumes, but do not quantitate severity of individual lesions. OBJECTIVE: Develop a method to differentiate black and gray holes and estimate the severity of individual multiple sclerosis lesions using standard magnetic resonance imaging...
December 2, 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29222800/primary-motor-neuron-culture-to-promote-cellular-viability-and-myelination
#2
Jun-Kyo Francis Suh, Sujin Hyung
A culture system that can recapitulate myelination in vitro will not only help us to better understand the mechanism of myelination and demyelination but also identify possible therapeutic interventions for treating demyelinating diseases. Here, we introduce a simple and reproducible myelination culture system using mouse motor neurons (MNs) and Schwann cells (SCs). Dissociated motor neurons are plated on a feeder layer of SCs, which interact with and wrap around the axons of MNs as they differentiate in culture...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29222794/active-induction-of-experimental-autoimmune-encephalomyelitis-in-c57bl-6-mice
#3
Gabriella Contarini, Pietro Giusti, Stephen D Skaper
The protocol in this chapter presents a method to actively induce experimental autoimmune encephalomyelitis (EAE), one of the most widely used animal models to study efficacy of potential drugs for treatment of multiple sclerosis. Multiple sclerosis is an inflammatory, demyelinating disease of the central nervous system and the most common cause of chronic neurological impairment in young people. In this model EAE is induced in female C57BL/6 mice by immunization with an emulsion of myelin oligodendrocyte glycoprotein (fragment 35-55) in complete Freund's adjuvant, followed by administration of pertussis toxin in phosphate-buffered saline...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29222419/probenecid-arrests-the-progression-of-pronounced-clinical-symptoms-in-a-mouse-model-of-multiple-sclerosis
#4
Nadine Hainz, Sandra Wolf, Artjom Beck, Stefan Wagenpfeil, Thomas Tschernig, Carola Meier
While it has been established that Probenecid (PBN) prevents the onset of experimental autoimmune encephalomyelitis (EAE) in mice, it is not clear whether it has any effect on already manifest EAE. The aim of this study was therefore to analyze the therapeutic effect of PBN in pronounced EAE. Mice with manifest clinical symptoms of EAE were either treated with PBN or solvent for 20 days, or they were left untreated. The clinical symptoms were monitored daily. Inflammation, demyelination and oligodendrocyte numbers were determined in the spinal cord...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29221753/pura-the-gene-encoding-pur-alpha-member-of-an-ancient-nucleic-acid-binding-protein-family-with-mammalian-neurological-functions
#5
REVIEW
Dianne C Daniel, Edward M Johnson
The PURA gene encodes Pur-alpha, a 322 amino acid protein with repeated nucleic acid binding domains that are highly conserved from bacteria through humans. PUR genes with a single copy of this domain have been detected so far in spirochetes and bacteroides. Lower eukaryotes possess one copy of the PUR gene, whereas chordates possess 1-4 PUR family members. Human PUR genes encode Pur-alpha (Pura), Pur-beta (Purb) and two forms of Pur-gamma (Purg). Pur-alpha is a protein that binds specific DNA and RNA sequence elements...
December 5, 2017: Gene
https://www.readbyqxmd.com/read/29217688/sustained-mapk-erk-activation-in-adult-schwann-cells-impairs-nerve-repair
#6
Ilaria Cervellini, Jorge Galino, Ning Zhu, Shannen Allen, Carmen Birchmeier, David L Bennett
The MAPK/ERK pathway has a critical role in PNS development. It is required for Schwann cell (SC) differentiation and myelination; sustained embryonic MAPK/ERK activation in SCs enhances myelin growth overcoming signals that normally end myelination. Excess activation of this pathway can be maladaptive as in adulthood acute strong activation of MAPK/ERK has been shown to cause SC dedifferentiation and demyelination. We used a mouse model (including male and female animals) in which gain of function Mek1DD allele produces sustained MAPK/ERK activation in adult SCs and we determined the impact of such activation on nerve repair...
December 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29217681/the-protein-tyrosine-phosphatase-shp2-regulates-oligodendrocyte-differentiation-and-early-myelination-and-contributes-to-timely-remyelination
#7
Jared T Ahrendsen, Danielle E Harlow, Lisbet T Finseth, Jennifer N Bourne, Sean P Hickey, Elizabeth A Gould, Cecilia M Culp, Wendy B Macklin
Shp2 is a nonreceptor protein tyrosine phosphatase that has been shown to influence neurogenesis, oligodendrogenesis, and oligodendrocyte differentiation. Furthermore, Shp2 is a known regulator of the Akt/mTOR and ERK signaling pathways in multiple cellular contexts, including oligodendrocytes. Its role during later postnatal CNS development or in response to demyelination injury has not been examined. Based on the current studies, we hypothesize that Shp2 is a negative regulator of CNS myelination. Using transgenic mouse technology, we show that Shp2 is involved in oligodendrocyte differentiation and early myelination, but is not necessary for myelin maintenance...
December 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29217679/miz1-controls-schwann-cell-proliferation-via-h3k36me2-demethylase-kdm8-to-prevent-peripheral-nerve-demyelination
#8
David Fuhrmann, Marco Mernberger, Andrea Nist, Thorsten Stiewe, Hans-Peter Elsässer
Schwann cell differentiation and myelination depends on chromatin remodeling, histone acetylation and methylation, which all have impact on Schwann cell proliferation. We previously reported that the deletion of the POZ domain of the transcription factor Miz1 (encoded by Zbtb17) in mouse Schwann cells (Miz1ΔPOZ) causes a neuropathy at 90 days after birth (P90), with a subsequent spontaneous regeneration. Here we show that RNA sequencing from Miz1ΔPOZ and control animals at P30 revealed a set of upregulated genes with a strong correlation to cell cycle regulation...
December 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29217470/safe-and-effective-interferon-beta-gene-therapy-for-the-treatment-of-multiple-sclerosis-by-regulating-biological-activity-through-the-design-of-interferon-beta-galectin-9-fusion-proteins
#9
Atsushi Hamana, Yuki Takahashi, Akane Tanioka, Makiya Nishikawa, Yoshinobu Takakura
Multiple sclerosis (MS) is the most common demyelinating disease. Despite the historical use of interferon-beta (IFN-β) for the treatment of patients with MS, concerns exist regarding the side effects of IFN-β. In this study, we designed a series of novel IFN-β fusion proteins containing galectin-9 (gal-9), which exerts immunosuppressive effects through the binding to its receptor on activated Th1 cells. We hypothesized that these fusion proteins would improve the therapeutic effects and reduce the side effects of IFN-β...
December 5, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29216327/protamine-neutralizes-chondroitin-sulfate-proteoglycan-mediated-inhibition-of-oligodendrocyte-differentiation
#10
Kazuya Kuboyama, Naomi Tanga, Ryoko Suzuki, Akihiro Fujikawa, Masaharu Noda
Chondroitin sulfate proteoglycans (CSPGs), which are enriched in demyelinating plaques in neurodegenerative diseases, such as multiple sclerosis (MS), impair remyelination by inhibiting the migration and differentiation of oligodendrocyte precursor cells (OPCs) in the central nervous system (CNS). We herein show that protamine (PRM, also known as a heparin antagonist) effectively neutralizes the inhibitory activities of CSPGs, thereby enhancing OPC differentiation and (re)myelination in mice. Cell-based assays using mouse OPC-like OL1 cells revealed that the PRM treatment exerted masking effects on extracellular CSPGs and improved oligodendrocyte differentiation on inhibitory CSPG-coated substrates...
2017: PloS One
https://www.readbyqxmd.com/read/29216010/calcitonin-gene-related-peptide-cgrp-role-in-peripheral-nerve-regeneration
#11
REVIEW
Albert M Chung
Calcitonin gene-related peptide (CGRP) is a neuropeptide that has an important anti-inflammatory role in the immune system. Research has shown that CGRP is an integral part in peripheral nerve regeneration by (1) suppressing tumor necrosis factor-α, (2) forming an initial nerve bridge by increasing fibroblast motility and extracellular matrix synthesis, (3) vascularizing the spinal cord injury site, and (4) inducing Schwann cell (SC) proliferation. In this treatise, the following hypotheses will be explored: (1) CGRP is induced by c-Jun to regulate SC dedifferentiation, (2) CGRP promotes the chemotaxic migration of SCs along the nerve bridge, and (3) CGRP induces myelinophagy by activating various signaling pathways, such as p38 mitogen-activated protein kinase and Raf/extracellular signal-regulated kinase...
December 7, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29215724/pericytes-modulate-myelination-in-the-central-nervous-system
#12
Patrick O Azevedo, Isadora F G Sena, Julia P Andreotti, Juliana Carvalho-Tavares, José C Alves-Filho, Thiago M Cunha, Fernando Q Cunha, Akiva Mintz, Alexander Birbrair
Multiple sclerosis is a highly prevalent chronic demyelinating disease of the central nervous system. Remyelination is the major therapeutic goal for this disorder. The lack of detailed knowledge about the cellular and molecular mechanisms involved in myelination restricts the design of effective treatments. De La Fuente et al. (2017) by using state-of-the-art techniques, including pericyte-deficient mice in combination with induced demyelination, reveal that pericytes participate in central nervous system regeneration...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29215409/imaging-of-acquired-demyelinating-syndrome-with-18f-fdg-pet-ct
#13
Caroline Malo-Pion, Raymond Lambert, Jean-Claude Décarie, Sophie Turpin
Acquired demyelinating syndromes include acute disseminated encephalomyelitis, transverse myelitis and may progress to multiple sclerosis (MS). Acute disseminated encephalomyelitis is characterized by impairment of level of consciousness and multifocal neurological deficits and transverse myelitis by back pain, weakness and sphincter dysfunction. Only a few cases of acquired demyelinating syndrome have been imaged with F-FDG PET/CT. We present two such cases.
December 5, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/29212956/icam1-neutrophils-promote-chronic-inflammation-via-asprv1-in-b-cell-dependent-autoimmune-encephalomyelitis
#14
Ryder F Whittaker Hawkins, Alexandre Patenaude, Aline Dumas, Rajiv Jain, Yodit Tesfagiorgis, Steven Kerfoot, Takeshi Matsui, Matthias Gunzer, Patrice E Poubelle, Catherine Larochelle, Martin Pelletier, Luc Vallières
Neutrophils contribute to demyelinating autoimmune diseases, yet their phenotype and functions have been elusive to date. Here, we demonstrate that ICAM1 surface expression distinguishes extra- from intravascular neutrophils in the mouse CNS during experimental autoimmune encephalomyelitis (EAE). Transcriptomic analysis of these 2 subpopulations indicated that neutrophils, once extravasated, acquire macrophage-like properties, including the potential for immunostimulation and MHC class II-mediated antigen presentation...
December 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/29212715/bcas1-expression-defines-a-population-of-early-myelinating-oligodendrocytes-in-multiple-sclerosis-lesions
#15
Maryam K Fard, Franziska van der Meer, Paula Sánchez, Ludovico Cantuti-Castelvetri, Sunit Mandad, Sarah Jäkel, Eugenio F Fornasiero, Sebastian Schmitt, Marc Ehrlich, Laura Starost, Tanja Kuhlmann, Christina Sergiou, Verena Schultz, Claudia Wrzos, Wolfgang Brück, Henning Urlaub, Leda Dimou, Christine Stadelmann, Mikael Simons
Investigations into brain function and disease depend on the precise classification of neural cell types. Cells of the oligodendrocyte lineage differ greatly in their morphology, but accurate identification has thus far only been possible for oligodendrocyte progenitor cells and mature oligodendrocytes in humans. We find that breast carcinoma amplified sequence 1 (BCAS1) expression identifies an oligodendroglial subpopulation in the mouse and human brain. These cells are newly formed, myelinating oligodendrocytes that segregate from oligodendrocyte progenitor cells and mature oligodendrocytes and mark regions of active myelin formation in development and in the adult...
December 6, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29211921/infections-and-the-relationship-to-treatment-in-neuromuscular-autoimmunity
#16
Devin E Prior, Emily Nurre, Stephanie L Roller, David Kline, Ramit Panara, Amro M Stino, John A Davis, Miriam L Freimer, W David Arnold
INTRODUCTION: This study aimed to identify infections in patients with myasthenia gravis, dermatomyositis and chronic inflammatory demyelinating polyradiculoneuropathy and investigate the relationship between infection and immunomodulation. METHODS: A retrospective chart review examined 631 patients with myasthenia gravis (n=358), chronic inflammatory demyelinating polyradiculoneuropathy (n=124), and dermatomyositis (n=149) patients over a 10 year time period. RESULTS: Infection rates were similar at approximately 19% in all three diseases...
December 6, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/29209169/amyloid-%C3%AE-homeostasis-bridges-inflammation-synaptic-plasticity-deficits-and-cognitive-dysfunction-in-multiple-sclerosis
#17
Mario Stampanoni Bassi, Sara Garofalo, Girolama A Marfia, Luana Gilio, Ilaria Simonelli, Annamaria Finardi, Roberto Furlan, Giulia M Sancesario, Jonny Di Giandomenico, Marianna Storto, Francesco Mori, Diego Centonze, Ennio Iezzi
Cognitive deficits are frequently observed in multiple sclerosis (MS), mainly involving processing speed and episodic memory. Both demyelination and gray matter atrophy can contribute to cognitive deficits in MS. In recent years, neuroinflammation is emerging as a new factor influencing clinical course in MS. Inflammatory cytokines induce synaptic dysfunction in MS. Synaptic plasticity occurring within hippocampal structures is considered as one of the basic physiological mechanisms of learning and memory. In experimental models of MS, hippocampal plasticity is profoundly altered by proinflammatory cytokines...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29207762/guillain-barre-syndrome-with-falciparum-malaria-and-scrub-typhus-mixed-infection-an-unusual-combination
#18
Rahul Sai Gangula, Weena Stanley, Arunsheshu Vandanapu, M Mukhyaprana Prabhu
Guillain-Barre Syndrome is very rare in parasitic and rickettsial infection. Here we report a case of Plasmodium falciparum and scrub typhus mixed infection, presented with quadriparesis. Clinical, Serological, CSF analysis and Nerve Conduction Studies were consistent with Acute Inflammatory Demyelinating Polyneuropathy (variant of GBS). After administration of antimalarials and antibiotics for the mixed infection, patient gradually improved.
September 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/29204292/serum-neurofilament-light-chain-in-nmosd-and-related-disorders-comparison-according-to-aquaporin-4-and-myelin-oligodendrocyte-glycoprotein-antibodies-status
#19
Mariotto S, Farinazzo A, Monaco S, Gajofatto A, Zanusso G, Schanda K, Capra R, Mancinelli C, Bonora A, Bombardi R, Reindl M, Ferrari S
Background: Neurofilament light chain (NF-L) levels reflect axonal damage in different conditions, including demyelinating disorders. Objectives: We aimed to compare serum NF-L levels in patients with aquaporin-4 antibodies (AQP4-Ab), myelin oligodendrocyte antibodies (MOG-Ab) and seronegative cases with neuromyelitis optica spectrum disorders and related disorders. Methods: We analysed AQP4-Ab and MOG-Ab with cell-based assay and NF-L with ultrasensitive electrochemiluminescence immunoassay...
October 2017: Multiple Sclerosis Journal—Experimental, Translational and Clinical
https://www.readbyqxmd.com/read/29204202/occult-disseminated-tuberculosis-with-holocord-longitudinally-extensive-transverse-myelitis-a-rare-phenomenon-in-a-child
#20
Gülsüm Alkan, Melike Emiroğlu, Ayşe Kartal, Harun Peru, Mustafa Koplay
Longitudinally extensive transverse myelitis (LETM) is defined as an inflammatory lesion of the spinal cord that extends to three or more segments. LETM is a commonly characteristic feature of neuromyelitis optica (NMO) or various autoimmune diseases. Manifestation of Mycobacterium tuberculosis (MTB) infection with LETM are rare and usually in the cervicothoracic spinal cord. Our patient presented with holocord LETM, so NMO was considered initially diagnosis. After in further research, MTB was diagnosed and treated successfully...
July 2017: Journal of Pediatric Neurosciences
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