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Neuroprotection in multiple sclerosis

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https://www.readbyqxmd.com/read/29057962/tnfr1-inhibition-with-a-nanobody-protects-against-eae-development-in-mice
#1
Sophie Steeland, Sara Van Ryckeghem, Griet Van Imschoot, Riet De Rycke, Wendy Toussaint, Leen Vanhoutte, Christian Vanhove, Filip De Vos, Roosmarijn E Vandenbroucke, Claude Libert
TNF has as detrimental role in multiple sclerosis (MS), however, anti-TNF medication is not working. Selective TNF/TNFR1 inhibition whilst sparing TNFR2 signaling reduces the pro-inflammatory effects of TNF but preserves the important neuroprotective signals via TNFR2. We previously reported the generation of a Nanobody-based selective inhibitor of human TNFR1, TROS that will be tested in experimental autoimmune encephalomyelitis (EAE). We specifically antagonized TNF/TNFR1 signaling using TROS in a murine model of MS, namely MOG35-55-induced EAE...
October 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29055473/the-effect-of-alcohol-and-red-wine-consumption-on-clinical-and-mri-outcomes-in-multiple-sclerosis
#2
Camilo Diaz-Cruz, Alicia S Chua, Muhammad Taimur Malik, Tamara Kaplan, Bonnie I Glanz, Svetlana Egorova, Charles R G Guttmann, Rohit Bakshi, Howard L Weiner, Brian C Healy, Tanuja Chitnis
BACKGROUND: Alcohol and in particular red wine have both immunomodulatory and neuroprotective properties, and may exert an effect on the disease course of multiple sclerosis (MS). OBJECTIVE: To assess the association between alcohol and red wine consumption and MS course. METHODS: MS patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB) who completed a self-administered questionnaire about their past year drinking habits at a single time point were included in the study...
October 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29055468/evaluation-of-lithium-serum-level-in-multiple-sclerosis-patients-a-neuroprotective-element
#3
Atieh Karimi, Kobra Bahrampour, Mohammad Amin Momeni Moghaddam, Gholamreza Asadikaram, Ghasem Ebrahimi, Masoud Torkzadeh-Mahani, Mojdeh Esmaeili Tarzi, Mohammad Hadi Nematollahi
INTRODUCTION: It has been claimed that continuous and high production of nitric oxide (NO) and its metabolites may be involved in the pathogenesis of several neurological disorders such as multiple sclerosis. A number of studies have demonstrated that lithium regulates NO levels in disorders of the central nervous system. The aim of this study was to investigate whether NO as a marker of disease activity is correlated with lithium deficiency in relapsing remitting multiple sclerosis (RR-MS)...
October 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29053779/cell-based-therapeutic-strategies-for-multiple-sclerosis
#4
Neil J Scolding, Marcelo Pasquini, Stephen C Reingold, Jeffrey A Cohen
The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis...
July 21, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29041867/patient-selection-for-trials
#5
Jerry S Wolinsky
The last several decades have witnessed considerable progress in our understanding of the pathogenesis, refining diagnostic criteria, and identifying therapies of value for modifying the course of relapsing forms of multiple sclerosis. While the pace of progress has lagged for those with progressive phase disease, this now seems to be changing. This review considers those characteristics of patients with primary progressive multiple sclerosis that may contribute to phase 3 trial success and identifies some of the thorny issues that remain ahead...
October 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29041865/imaging-outcome-measures-for-progressive-multiple-sclerosis-trials
#6
Marcello Moccia, Nicola de Stefano, Frederik Barkhof
Imaging markers that are reliable, reproducible and sensitive to neurodegenerative changes in progressive multiple sclerosis (MS) can enhance the development of new medications with a neuroprotective mode-of-action. Accordingly, in recent years, a considerable number of imaging biomarkers have been included in phase 2 and 3 clinical trials in primary and secondary progressive MS. Brain lesion count and volume are markers of inflammation and demyelination and are important outcomes even in progressive MS trials...
October 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29041864/targets-of-therapy-in-progressive-ms
#7
Hans Lassmann
Highly effective anti-inflammatory therapies have so far been developed for patients with relapsing/remitting multiple sclerosis, which also show some benefits in the early progressive stage of the disease. However, treatment options for patients, who have entered the progressive phase, are still limited. Disease starts as an inflammatory process, which induces focal demyelinating lesions in the gray and white matter. This stage of the disease dominates in the relapsing phase, extends into the early stages of progressive disease, and can be targeted by current anti-inflammatory treatments...
October 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29041863/clinical-outcome-measures-for-progressive-ms-trials
#8
Daniel Ontaneda, Jeffrey A Cohen, Maria Pia Amato
Treatment options for progressive multiple sclerosis remain the main unmet need of the field. As the understanding of multiple sclerosis (MS) pathogenesis improves, new pathways and molecules will be tested for potential reparative, remyelinating, or neuroprotective effects. The clinical outcomes used will determine successful demonstration of beneficial treatment effects to regulatory agencies, clinicians, and persons with MS. This review focuses on clinical outcome measures including the Expanded Disability Status Scale, Multiple Sclerosis Functional Composite, and novel composite measures of disability...
October 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29029628/erythropoietin-reduces-experimental-autoimmune-encephalomyelitis-severity-via-neuroprotective-mechanisms
#9
M Moransard, M Bednar, K Frei, M Gassmann, O O Ogunshola
BACKGROUND: Treatment with erythropoietin (Epo) in experimental autoimmune encephalomyelitis (EAE), the rodent model of multiple sclerosis (MS), has consistently been shown to ameliorate disease progression and improve overall outcome. The effect has been attributed to modulation of the immune response and/or preservation of the central nervous system (CNS) tissue integrity. It remains unclear, however, if (a) Epo acts primarily in the CNS or the periphery and if (b) Epo's beneficial effect in EAE is mainly due to maintaining CNS tissue integrity or to modulation of the immune response...
October 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28955296/spinocerebellar-ataxia-type-2-clinicogenetic-aspects-mechanistic-insights-and-management-approaches
#10
REVIEW
Luis C Velázquez-Pérez, Roberto Rodríguez-Labrada, Juan Fernandez-Ruiz
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant cerebellar ataxia that occurs as a consequence of abnormal CAG expansions in the ATXN2 gene. Progressive clinical features result from the neurodegeneration of cerebellum and extra-cerebellar structures including the pons, the basal ganglia, and the cerebral cortex. Clinical, electrophysiological, and imaging approaches have been used to characterize the natural history of the disease, allowing its classification into four distinct stages, with special emphasis on the prodromal stage, which is characterized by a plethora of motor and non-motor features...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28939905/expression-and-differential-responsiveness-of-central-nervous-system-glial-cell-populations-to-the-acute-phase-protein-serum-amyloid-a
#11
Massimo Barbierato, Mila Borri, Laura Facci, Morena Zusso, Stephen D Skaper, Pietro Giusti
Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves hepatic production of acute-phase proteins, including serum amyloid A (SAA). Extrahepatically, SAA immunoreactivity is found in axonal myelin sheaths of cortex in Alzheimer's disease and multiple sclerosis (MS), although its cellular origin is unclear. We examined the responses of cultured rat cortical astrocytes, microglia and oligodendrocyte precursor cells (OPCs) to master pro-inflammatory cytokine tumour necrosis factor (TNF)-α and lipopolysaccaride (LPS)...
September 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28939293/dose-dependent-s-allyl-cysteine-ameliorates-multiple-sclerosis-disease-related-pathology-by-reducing-oxidative-stress-and-biomarkers-of-dysbiosis-in-experimental-autoimmune-encephalomyelitis
#12
B M Escribano, E Luque, M Aguilar-Luque, M Feijóo, J Caballero-Villarraso, L A Torres, V Ramirez, F I García-Maceira, E Agüera, A Santamaria, I Túnez
Garlic is a component of the Mediterranean diet. S-allyl cysteine (SAC), the most common organosulphur present in garlic, possesses neuroprotective properties. This investigation was performed to evaluate the dose-dependent protective action of SAC on oxidative damage, inflammation and gut microbiota alterations biomarkers. Experimental autoimmune encephalomyelitis (EAE) as a model of multiple sclerosis (MS) was induced by the myelin oligodendrocyte glycoprotein (MOG), whose effects were quantified by examining the changes in: clinical score, lipid peroxidation products, carbonylated proteins, glutathione system, tumor necrosis factor alpha (TNFα), and lipopolysaccharide membrane bacteria (LPS)...
September 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28931570/mitochondrial-dna-double-strand-breaks-in-oligodendrocytes-cause-demyelination-axonal-injury-and-cns-inflammation
#13
Pernille M Madsen, Milena Pinto, Shreyans Patel, Stephanie McCarthy, Han Gao, Mehran Taherian, Shaffiat Karmally, Claudia V Pereira, Galina Dvoriantchikova, Dmitry Ivanov, Kenji F Tanaka, Carlos T Moraes, Roberta Brambilla
Mitochondrial dysfunction has been implicated in the pathophysiology of neurodegenerative disorders, including multiple sclerosis (MS). To date, the investigation of mitochondrial dysfunction in MS has focused exclusively on neurons, with no studies exploring whether dysregulation of mitochondrial bioenergetics and/or genetics in oligodendrocytes might be associated with the etiopathogenesis of MS and other demyelinating syndromes. To address this question, we established a mouse model where mitochondrial DNA (mtDNA) double-strand breaks (DSB) were specifically induced in myelinating oligodendrocytes (PLP:mtPstI mice) by expressing a mitochondrial-targeted endonuclease, mtPstI, starting at 3 weeks of age...
September 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28923363/anti-inflammatory-effects-of-flavonoids-in-neurodegenerative-disorders
#14
Carmela Spagnuolo, Stefania Moccia, Gian Luigi Russo
Neuroinflammation is one of the main mechanisms involved in the progression of several neurodegenerative diseases, such as Parkinson, Alzheimer, multiple sclerosis, amyotrophic lateral sclerosis and others. The activation of microglia is the main feature of neuroinflammation, promoting the release of pro-inflammatory cytokines and resulting in the progressive neuronal cell death. Natural compounds, such as flavonoids, possess neuroprotective potential probably related to their ability to modulate the inflammatory responses involved in neurodegenerative diseases...
September 7, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28921587/dimethyl-fumarate-treatment-after-traumatic-brain-injury-prevents-depletion-of-antioxidative-brain-glutathione-and-confers-neuroprotection
#15
Tobias Krämer, Theresa Grob, Lutz Menzel, Tobias Hirnet, Eva Griemert, Konstantin Radyushkin, Serge C Thal, Axel Methner, Michael K E Schaefer
Dimethyl fumarate (DMF) is an immunomodulatory therapeutic for multiple sclerosis and psoriasis with neuroprotective potential. Its mechanism of action involves activation of the antioxidant pathway regulator Nuclear factor erythroid 2-related factor 2 (Nrf2) thereby increasing synthesis of the cellular antioxidant glutathione (GSH). The objective of this study was to investigate whether post-traumatic DMF treatment is beneficial after experimental traumatic brain injury (TBI). Adult C57Bl/6 mice were subjected to controlled cortical impact followed by oral administration of DMF (80 mg/kg body weight) or vehicle at 3 h, 24 h, 48 h and 72 h after the inflicted TBI...
September 16, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28917625/reduced-neuroprotective-potential-of-the-mesenchymal-stromal-cell-secretome-with-ex-vivo-expansion-age-and-progressive-multiple-sclerosis
#16
Pamela Sarkar, Juliana Redondo, Kevin Kemp, Mark Ginty, Alastair Wilkins, Neil J Scolding, Claire M Rice
BACKGROUND: Clinical trials using ex vivo expansion of autologous mesenchymal stromal cells (MSCs) are in progress for several neurological diseases including multiple sclerosis (MS). Given that environment alters MSC function, we examined whether in vitro expansion, increasing donor age and progressive MS affect the neuroprotective properties of the MSC secretome. METHODS: Comparative analyses of neuronal survival in the presence of MSC-conditioned medium (MSCcm) isolated from control subjects (C-MSCcm) and those with MS (MS-MSCcm) were performed following (1) trophic factor withdrawal and (2) nitric oxide-induced neurotoxicity...
September 13, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28913617/fingolimod-induces-neuronal-specific-gene-expression-with-potential-neuroprotective-outcomes-in-maturing-neuronal-progenitor-cells-exposed-to-hiv
#17
Rebeca Geffin, Ricardo Martinez, Alicia de Las Pozas, Biju Issac, Micheline McCarthy
Fingolimod (FTY720), a structural analogue of sphingosine, targets sphingosine-1-phosphate receptor signaling and is currently an immunomodulatory therapy for multiple sclerosis. Fingolimod accesses the central nervous system (CNS) where its active metabolite, fingolimod phosphate (FTY720-P), has pleotropic neuroprotective effects in an inflammatory microenvironment. To investigate potential neuronal-specific mechanisms of fingolimod neuroprotection, we cultured the human neuronal progenitor cell line, hNP1, in differentiation medium supplemented with HIV- or Mock-infected supernatants, with or without FTY720-P...
September 14, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28911655/therapeutic-effects-of-d-aspartate-in-a-mouse-model-of-multiple-sclerosis
#18
Sanaz Afraei, Antimo D'Aniello, Reza Sedaghat, Parvin Ekhtiari, Gholamreza Azizi, Nakisa Tabrizian, Laura Magliozzi, Zahra Aghazadeh, Abbas Mirshafiey
Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis. EAE is mainly mediated by adaptive and innate immune responses that leads to an inflammatory demyelization and axonal damage. The aim of the present research was to examine the therapeutic efficacy of D-aspartic acid (D-Asp) on a mouse EAE model. EAE induction was performed in female C57BL/6 mice by myelin 40 oligodendrocyte glycoprotein (35-55) in a complete Freund's adjuvant emulsion, and D-Asp was used to test its efficiency in the reduction of EAE...
July 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28904554/plants-derived-neuroprotective-agents-cutting-the-cycle-of-cell-death-through-multiple-mechanisms
#19
REVIEW
Taiwo Olayemi Elufioye, Tomayo Ireti Berida, Solomon Habtemariam
Neuroprotection is the preservation of the structure and function of neurons from insults arising from cellular injuries induced by a variety of agents or neurodegenerative diseases (NDs). The various NDs including Alzheimer's, Parkinson's, and Huntington's diseases as well as amyotropic lateral sclerosis affect millions of people around the world with the main risk factor being advancing age. Each of these diseases affects specific neurons and/or regions in the brain and involves characteristic pathological and molecular features...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28894435/neuroactive-steroids-receptor-interactions-and-responses
#20
REVIEW
Kald Beshir Tuem, Tesfay Mehari Atey
Neuroactive steroids (NASs) are naturally occurring steroids, which are synthesized centrally as de novo from cholesterol and are classified as pregnane, androstane, and sulfated neurosteroids (NSs). NASs modulate many processes via interacting with gamma-aminobutyric acid (GABA), N-methyl-d-aspartate, serotonin, voltage-gated calcium channels, voltage-dependent anion channels, α-adrenoreceptors, X-receptors of the liver, transient receptor potential channels, microtubule-associated protein 2, neurotrophin nerve growth factor, and σ1 receptors...
2017: Frontiers in Neurology
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