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Neuroprotection in multiple sclerosis

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https://www.readbyqxmd.com/read/28423529/pif-promotes-brain-re-myelination-locally-while-regulating-systemic-inflammation-clinically-relevant-multiple-sclerosis-m-smegmatis-model
#1
Giuseppe Migliara, Martin Mueller, Alessia Piermattei, Chaya Brodie, Michael J Paidas, Eytan R Barnea, Francesco Ria
Neurologic disease diagnosis and treatment is challenging. Multiple Sclerosis (MS) is a demyelinating autoimmune disease with few clinical forms and uncertain etiology. Current studies suggest that it is likely caused by infection(s) triggering a systemic immune response resulting in antigen/non-antigen-related autoimmune response in central nervous system (CNS). New therapeutic approaches are needed. Secreted by viable embryos, PreImplantation Factor (PIF) possesses a local and systemic immunity regulatory role...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422748/therapeutic-inhibition-of-soluble-brain-tnf-promotes-remyelination-by-increasing-myelin-phagocytosis-by-microglia
#2
Maria Karamita, Christopher Barnum, Wiebke Möbius, Malú G Tansey, David E Szymkowski, Hans Lassmann, Lesley Probert
Multiple sclerosis (MS) is an inflammatory CNS demyelinating disease in which remyelination largely fails. Transmembrane TNF (tmTNF) and TNF receptor 2 are important for remyelination in experimental MS models, but it is unknown whether soluble TNF (solTNF), a major proinflammatory factor, is involved in regeneration processes. Here, we investigated the specific contribution of solTNF to demyelination and remyelination in the cuprizone model. Treatment with XPro1595, a selective inhibitor of solTNF that crosses the intact blood-brain barrier (BBB), in cuprizone-fed mice did not prevent toxin-induced oligodendrocyte loss and demyelination, but it permitted profound early remyelination due to improved phagocytosis of myelin debris by CNS macrophages and prevented disease-associated decline in motor performance...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28412918/neurological-aspects-of-medical-use-of-cannabidiol
#3
Carmen Mannucci, Michele Navarra, Fabrizio Calapai, Elvira Ventura Spagnolo, Francesco Paolo Busardò, Roberto Da Cas, Francesca Menniti Ippolito, Gioacchino Calapai
BACKGROUND: Cannabidiol (CBD) is among the major secondary metabolites of Cannabis devoid of the delta-9-tetra-hydrocannabinol psychoactive effects. It is a resorcinol-based compound with a broad spectrum of potential therapeutic properties, including neuroprotective effects in numerous pathological conditions. CBD neuroprotection is due to its antioxidant and antiinflammatory activi-ties and the modulation of a large number of brain biological targets (receptors, channels) involved in the development and maintenance of neurodegenerative diseases...
April 13, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28397112/cell-therapy-for-multiple-sclerosis
#4
REVIEW
Pamela Sarkar, Claire M Rice, Neil J Scolding
Cell therapy is considered a promising potential treatment for multiple sclerosis, perhaps particularly for the progressive form of the disease for which there are currently no useful treatments. Over the past two decades or more, much progress has been made in understanding the biology of MS and in the experimental development of cell therapy for this disease. Three quite distinct forms of cell therapy are currently being pursued. The first seeks to use stem cells to replace damaged myelin-forming oligodendrocytes within the CNS; the second aims, in effect, to replace the individual's misfunctioning immune system, making use of haematopoietic stem cells; and the third seeks to utilise endogenous stem cell populations by mobilisation with or without in vitro expansion, exploiting their various reparative and neuroprotective properties...
April 10, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28394203/dysregulation-of-energy-metabolism-in-multiple-sclerosis-measured-in-vivo-with-diffusion-weighted-spectroscopy
#5
Benedetta Bodini, Francesca Branzoli, Emilie Poirion, Daniel García-Lorenzo, Mélanie Didier, Elisabeth Maillart, Julie Socha, Geraldine Bera, Catherine Lubetzki, Itamar Ronen, Stephane Lehericy, Bruno Stankoff
OBJECTIVE: We employed diffusion-weighted magnetic resonance spectroscopy (DW-MRS), which allows to measure in vivo the diffusion properties of metabolites, to explore the functional neuro-axonal damage and the ongoing energetic dysregulation in multiple sclerosis (MS). METHODS: Twenty-five patients with MS and 18 healthy controls (HC) underwent conventional magnetic resonance imaging (MRI) and DW-MRS. The apparent diffusion coefficient (ADC) of total N-acetyl-aspartate (tNAA) and creatine-phosphocreatine (tCr) were measured in the parietal normal-appearing white matter (NAWM) and in the thalamic grey matter (TGM)...
April 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28387380/a-staged-screening-of-registered-drugs-highlights-remyelinating-drug-candidates-for-clinical-trials
#6
C Eleuteri, S Olla, C Veroni, R Umeton, R Mechelli, S Romano, M C Buscarinu, F Ferrari, G Calò, G Ristori, M Salvetti, C Agresti
There is no treatment for the myelin loss in multiple sclerosis, ultimately resulting in the axonal degeneration that leads to the progressive phase of the disease. We established a multi-tiered platform for the sequential screening of drugs that could be repurposed as remyelinating agents. We screened a library of 2,000 compounds (mainly Food and Drug Administration (FDA)-approved compounds and natural products) for cellular metabolic activity on mouse oligodendrocyte precursors (OPC), identifying 42 molecules with significant stimulating effects...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28381594/nimodipine-fosters-remyelination-in-a-mouse-model-of-multiple-sclerosis-and-induces-microglia-specific-apoptosis
#7
Andrea Schampel, Oleg Volovitch, Tobias Koeniger, Claus-Jürgen Scholz, Stefanie Jörg, Ralf A Linker, Erhard Wischmeyer, Marie Wunsch, Johannes W Hell, Süleyman Ergün, Stefanie Kuerten
Despite continuous interest in multiple sclerosis (MS) research, there is still a lack of neuroprotective strategies, because the main focus has remained on modulating the immune response. Here we performed in-depth analysis of neurodegeneration in experimental autoimmune encephalomyelitis (EAE) and in in vitro studies regarding the effect of the well-established L-type calcium channel antagonist nimodipine. Nimodipine treatment attenuated clinical EAE and spinal cord degeneration and promoted remyelination...
April 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28374232/monitoring-the-course-of-ms-with-optical-coherence-tomography
#8
REVIEW
Alexander U Brandt, Elena H Martinez-Lapiscina, Rachel Nolan, Shiv Saidha
Retinae of patients with multiple sclerosis (MS), as part of the central nervous system (CNS), display inflammatory and neurodegenerative changes. There is increasing evidence suggesting that retinal changes, and in particular neurodegeneration, mirror global CNS alterations in MS. Spectral domain optical coherence tomography (SD-OCT) is an inexpensive, rapid, non-invasive, and reproducible imaging technique that generates high-resolution images of tissues such as the retina. An advantage of SD-OCT over magnetic resonance imaging techniques in the assessment of neurodegeneration may be its sensitivity to capture changes at the individual patient level...
April 2017: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/28369944/increasing-acetyl-coa-metabolism-attenuates-injury-and-alters-spinal-cord-lipid-content-in-mice-subjected-to-experimental-autoimmune-encephalomyelitis
#9
Amber C Chevalier, Thad A Rosenberger
Acetate supplementation increases brain acetyl-CoA metabolism, alters histone and non-histone protein acetylation, increases brain energy reserves, and is anti-inflammatory and neuroprotective in rat models of neuroinflammation and neuroborreliosis. To determine the impact acetate supplementation has on a mouse model of multiple sclerosis, we quantified the effect treatment had on injury progression, spinal cord lipid content, phospholipase levels, and myelin structure in mice subjected to experimental autoimmune encephalomyelitis (EAE)...
March 31, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28363412/fty720-derivatives-do-not-induce-fty720-like-lymphopenia
#10
Ismael Segura-Ulate, Troy K Belcher, Guadalupe Vidal-Martinez, Javier Vargas-Medrano, Ruth G Perez
FTY720 is an immunosuppressive multiple sclerosis (MS) drug that stimulates the expression of neuroprotective brain-derived-neurotrophic-factor (BDNF). In vivo preclinical data suggest that FTY720 could be beneficial for treating Parkinson's patients, though its immunosuppressive effects might limit its efficacy. Two novel FTY720-derivatives, FTY720-C2 and FTY720-Mitoxy, also stimulate BDNF expression and enter brain like FTY720 but are not phosphorylated, suggesting they will not produce FTY720-like immunosuppression...
March 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28362719/imaging-markers-of-multiple-sclerosis-prognosis
#11
Céline Louapre, Benedetta Bodini, Catherine Lubetzki, Léorah Freeman, Bruno Stankoff
PURPOSE OF REVIEW: Studies of large longitudinal cohorts of patients with multiple sclerosis (MS) have emphasized the prognostic value of conventional MRI markers, at least during early stages. Advanced imaging metrics derived from quantitative MRI and PET provide relevant information about microstructural damage within and outside visible lesions that may be more sensitive to predict long-term disability. Here, we summarize the most recent findings regarding the prognostic value of imaging markers throughout MS stages...
March 30, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28350081/morroniside-protects-sk-n-sh-human-neuroblastoma-cells-against-h2o2-induced-damage
#12
Jing-Xing Zhang, Rui Wang, Jin Xi, Lin Shen, An-You Zhu, Qi Qi, Qi-Yi Wang, Lun-Jun Zhang, Feng-Chao Wang, He-Zuo Lü, Jian-Guo Hu
Oxidative stress-induced cell injury has been linked to the pathogenesis of neurodegenerative disorders such as spinal cord injury, Parkinson's disease, and multiple sclerosis. Morroniside is an antioxidant derived from the Chinese herb Shan-Zhu-Yu. The present study investigated the neuroprotective effect of morroniside against hydrogen peroxide (H2O2)-induced cell death in SK-N-SH human neuroblastoma cells. H2O2 increased cell apoptosis, as determined by flow cytometry and Hoechst 33342 staining. This effect was reversed by pretreatment with morroniside at concentrations of 1-100 µM...
February 8, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28343295/identification-of-sphingosine-1-phosphate-receptor-subtype-1-s1p1-as-a-pathogenic-factor-in-transient-focal-cerebral-ischemia
#13
Bhakta Prasad Gaire, Chi-Ho Lee, Arjun Sapkota, Sang Yeul Lee, Jerold Chun, Hee Jun Cho, Tae-Gyu Nam, Ji Woong Choi
Medically relevant roles of receptor-mediated sphingosine 1-phosphate (S1P) signaling have become a successful or promising target for multiple sclerosis or cerebral ischemia. Animal-based proof-of-concept validation for the latter is particularly through the neuroprotective efficacy of FTY720, a non-selective S1P receptor modulator, presumably via activation of S1P1. In spite of a clear link between S1P signaling and cerebral ischemia, it remains unknown whether the role of S1P1 is pathogenic or neuroprotective...
March 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28338498/challenge-of-progressive-multiple-sclerosis-therapy
#14
Alan J Thompson
PURPOSE OF REVIEW: Understanding the mechanisms underlying progression in multiple sclerosis (MS) and identifying appropriate therapeutic targets is a key challenge facing the MS community. This challenge has been championed internationally by organizations such as the Progressive MS Alliance, which has raised the profile of progressive MS and identified the key obstacles to treatment. This review will outline the considerable progress against these challenges. RECENT FINDINGS: New insights into mechanisms underlying progression have opened up potential therapeutic opportunities...
March 23, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28320113/alzheimer-s-disease-elevated-pigment-epithelium-derived-factor-in-the-cerebrospinal-fluid-is-mostly-of-systemic-origin
#15
Veronika Lang, Marietta Zille, Carmen Infante-Duarte, Sven Jarius, Holger Jahn, Friedemann Paul, Klemens Ruprecht, Ana Luisa Pina
Pigment-epithelium derived factor (PEDF) is a neurotrophic factor with neuroprotective, anti-tumorigenic, and anti-angiogenic effects. Elevated levels of PEDF have previously been proposed as a cerebrospinal fluid (CSF) biomarker for Alzheimer's disease. However, the origin of PEDF in CSF, i.e. whether it is derived from the brain or from the systemic circulation, and the specificity of this finding hitherto remained unclear. Here, we analyzed levels of PEDF in paired CSF and serum samples by ELISA in patients with Alzheimer's disease (AD, n=12), frontotemporal dementia (FTD, n=6), vascular dementia (n=4), bacterial meningitis (n=8), multiple sclerosis (n=32), pseudotumor cerebri (n=36), and diverse non-inflammatory neurological diseases (n=19)...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28315275/sigma-1-receptor-in-motoneuron-disease
#16
Renzo Mancuso, Xavier Navarro
Amyotrophic Lateral Sclerosis (ALS ) is a neurodegenerative disease affecting spinal cord and brain motoneurons , leading to paralysis and early death. Multiple etiopathogenic mechanisms appear to contribute in the development of ALS , including glutamate excitotoxicity, oxidative stress , protein misfolding, mitochondrial defects, impaired axonal transport, inflammation and glial cell alterations. The Sigma-1 receptor is highly expressed in motoneurons of the spinal cord, particularly enriched in the endoplasmic reticulum (ER) at postsynaptic cisternae of cholinergic C-terminals...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28303450/dr%C3%AE-1-mog-35-55-treatment-reduces-lesion-volumes-and-improves-neurological-deficits-after-traumatic-brain-injury
#17
Liu Yang, Zhijia Liu, Honglei Ren, Lei Zhang, Siman Gao, Li Ren, Zhi Chai, Roberto Meza-Romero, Gil Benedek, Arthur A Vandenbark, Halina Offner, Minshu Li
Traumatic brain injury (TBI) results in severe neurological impairments without effective treatments. Inflammation appears to be an important contributor to key pathogenic events such as secondary brain injury following TBI and therefore serves as a promising target for novel therapies. We have recently demonstrated the ability of a molecular construct comprised of the human leukocyte antigen (HLA)-DRα1 domain linked covalently to mouse (m)MOG-35-55 peptide (DRα1-MOG-35-55 construct) to reduce CNS inflammation and tissue injury in animal models of multiple sclerosis and ischemic stroke...
March 16, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28302135/myeloid-c-ebp%C3%AE-deficiency-reshapes-microglial-gene-expression-and-is-protective-in-experimental-autoimmune-encephalomyelitis
#18
Marta Pulido-Salgado, Jose M Vidal-Taboada, Gerardo Garcia Diaz-Barriga, Joan Serratosa, Tony Valente, Paola Castillo, Jonathan Matalonga, Marco Straccia, Josep M Canals, Annabel Valledor, Carme Solà, Josep Saura
BACKGROUND: CCAAT/enhancer binding protein β (C/EBPβ) is a transcription factor that regulates the expression of important pro-inflammatory genes in microglia. Mice deficient for C/EBPβ show protection against excitotoxic and ischemic CNS damage, but the involvement in this neuroprotective effect of the various C/EBPβ-expressing cell types is not solved. Since C/EBPβ-deficient microglia show attenuated neurotoxicity in culture, we hypothesized that specific C/EBPβ deficiency in microglia could be neuroprotective in vivo...
March 16, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28302008/mitochondria-targeted-antioxidants-as-a-prospective-therapeutic-strategy-for-multiple-sclerosis
#19
Elena K Fetisova, Boris V Chernyak, Galina A Korshunova, Maria S Muntyan, Vladimir P Skulachev
BACKGROUND: Multiple sclerosis (MS) is one of the most widespread chronic neurological diseases that manifests itself by progressive demyelination in the central nervous system. The study of MS pathogenesis begins with the onset of the relapsing-remitting phase of the disease, which becomes apparent due to microglia activation, neuroinflammation and demyelination/remyelination in the white matter. The following progressive phase is accompanied by severe neurological symptoms when demyelination and neurodegeneration are spread to both gray and white matter...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28301040/dimercaprol-is-an-acrolein-scavenger-that-mitigates-acrolein-mediated-pc-12-cells-toxicity-and-reduces-acrolein-in-rat-following-spinal-cord-injury
#20
Ran Tian, Riyi Shi
Acrolein is one of the most toxic byproducts of lipid peroxidation, and it has been shown to be associated with multiple pathological processes in trauma and diseases, including spinal cord injury, multiple sclerosis, and Alzheimer's disease. Therefore, suppressing acrolein using acrolein scavengers has been suggested as a novel strategy of neuroprotection. In an effort to identify effective acrolein scavengers, we have confirmed that dimercaprol, which possesses thiol functional groups, could bind and trap acrolein...
March 16, 2017: Journal of Neurochemistry
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