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Neuroprotection in multiple sclerosis

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https://www.readbyqxmd.com/read/27904492/hydroxycitric-acid-ameliorates-inflammation-and-oxidative-stress-in-mouse-models-of-multiple-sclerosis
#1
Mahdi Goudarzvand, Sanaz Afraei, Somaye Yaslianifard, Saleh Ghiasy, Ghazal Sadri, Mustafa Kalvandi, Tina Alinia, Ali Mohebbi, Reza Yazdani, Shahin Khadem Azarian, Abbas Mirshafiey, Gholamreza Azizi
Hydroxycitric acid (HCA) is derived primarily from the Garcinia plant and is widely used for its anti-inflammatory effects. Multiple sclerosis can cause an inflammatory demyelination and axonal damage. In this study, to validate the hypothesis that HCA exhibits therapeutic effects on multiple sclerosis, we established female C57BL/6 mouse models of multiple sclerosis, i.e., experimental autoimmune encephalomyelitis, using Complete Freund's Adjuvant (CFA) emulsion containing myelin oligodendrocyte glycoprotein (35-55)...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27889959/fumaric-acid-esters-attenuate-secondary-degeneration-following-spinal-cord-injury
#2
Marika Cordaro, Giovanna Casili, Irene Paterniti, Salvatore Cuzzocrea, Emanuela Esposito
Spinal cord injury (SCI) causes permanent changes in motor, sensory and autonomic functions. Unfortunately, there are not a stable cures and current treatments include surgical decompression, methylprednisolone and hemodynamic control that lead to modest function recovery. Fumaric acid esters (FAEs) were firstly used in the management of an immunological skin disorder, such as psoriasis. Because of their potent anti-inflammatory effects, they have been introduced in multiple sclerosis. Investigation shown not only anti-inflammatory, but also supposed neuroprotective mechanism of action...
November 27, 2016: Journal of Neurotrauma
https://www.readbyqxmd.com/read/27882351/activity-of-nav1-2-promotes-neurodegeneration-in-an-animal-model-of-multiple-sclerosis
#3
Benjamin Schattling, Walid Fazeli, Birgit Engeland, Yuanyuan Liu, Holger Lerche, Dirk Isbrandt, Manuel A Friese
Counteracting the progressive neurological disability caused by neuronal and axonal loss is the major unmet clinical need in multiple sclerosis therapy. However, the mechanisms underlying irreversible neuroaxonal degeneration in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE) are not well understood. A long-standing hypothesis holds that the distribution of voltage-gated sodium channels along demyelinated axons contributes to neurodegeneration by increasing neuroaxonal sodium influx and energy demand during CNS inflammation...
November 17, 2016: JCI Insight
https://www.readbyqxmd.com/read/27876534/transcranial-magnetic-stimulation-modifies-astrocytosis-cell-density-and-lipopolysaccharide-levels-in-experimental-autoimmune-encephalomyelitis
#4
Francisco J Medina-Fernández, Evelio Luque, Macarena Aguilar-Luque, Eduardo Agüera, Montserrat Feijóo, Fe I García-Maceira, Begoña M Escribano, Álvaro Pascual-Leone, René Drucker-Colín, Isaac Túnez
AIMS: Experimental autoimmune encephalomyelitis (EAE) is considered a valid experimental model for multiple sclerosis, a chronic neuroinflammatory condition of the central nervous system. Additionally, some evidence has shown that some microbial products such as the bacterial lipopolysaccharide could lead to the activation of reactive immune cells, triggering neuroinflammation. Several studies have found that transcranial magnetic stimulation (TMS) may exert a neuroprotective effect. Therefore, we aimed to assess the effect of TMS on the neuroinflammation occurring in EAE...
November 19, 2016: Life Sciences
https://www.readbyqxmd.com/read/27865736/ips-derived-neural-progenitor-cells-from-ppms-patients-reveal-defect-in-myelin-injury-response
#5
Alexandra M Nicaise, Erin Banda, Rosa M Guzzo, Kristen Russomanno, Wanda Castro-Borrero, Cory M Willis, Kasey M Johnson, Albert C Lo, Stephen J Crocker
Primary progressive multiple sclerosis (PPMS) is a chronic demyelinating disease of the central nervous system (CNS) currently lacking any effective treatment. Promoting endogenous brain repair offers a potential strategy to halt and possibly restore neurologic function in PPMS. To understand how the microenvironment within white matter lesions plays a role in repair we have focused on neural progenitor cells (NPCs) since these are found in lesions in PPMS and have been found to influence oligodendrocyte progenitor cell maturation (OPCs)...
November 16, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27829982/new-insights-into-the-role-of-oxidative-stress-mechanisms-in-the-pathophysiology-and-treatment-of-multiple-sclerosis
#6
REVIEW
Bożena Adamczyk, Monika Adamczyk-Sowa
Multiple sclerosis (MS) is a multifactorial disease of the central nervous system (CNS) characterized by an inflammatory process and demyelination. The etiology of the disease is still not fully understood. Therefore, finding new etiological factors is of such crucial importance. It is suspected that the development of MS may be affected by oxidative stress (OS). In the acute phase OS initiates inflammatory processes and in the chronic phase it sustains neurodegeneration. Redox processes in MS are associated with mitochondrial dysfunction, dysregulation of axonal bioenergetics, iron accumulation in the brain, impaired oxidant/antioxidant balance, and OS memory...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27823573/the-sphingosine-1-phosphate-signaling-pathway-in-epilepsy-a-possible-role-for-the-immunomodulator-drug-fingolimod-in-epilepsy-treatment
#7
Antonio Leo, Rita Citraro, Rosario Marra, Ernesto Palma, Eugenio Donato Di Paola, Andrew Constanti, Giovambattista De Sarro, Emilio Russo
It is currently known that erythrocytes are the major source of sphingosine 1-phosphate (S1P) in the body. S1P acts both extracellularly as a cellular mediator and intracellularly as an important second messenger molecule. Its effects are mediated by interaction with five specific types of G protein-coupled S1P receptor. Fingolimod, is a recognized modulator of S1P receptors, and is the first orally active disease-modifying therapy that has been approved for the treatment of multiple sclerosis. Magnetic resonance imaging data suggest that fingolimod may be effective in multiple sclerosis MS by preventing blood-brain barrier disruption and brain atrophy...
November 4, 2016: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/27813441/primary-progressive-multiple-sclerosis-current-therapeutic-strategies-and-future-perspectives
#8
Alberto Gajofatto, Marco Turatti, Maria Donata Benedetti
Multiple sclerosis (MS) is a chronic inflammatory condition of the central nervous system with heterogeneous features. Primary progressive (PP) MS is a rare disease subtype characterized by continuous disability worsening from onset. No disease-modifying therapy is currently approved for PP MS due to the negative or inconsistent results of clinical trials conducted on a wide range of interventions, which are reviewed in the present paper. Areas covered: The features and results of randomized trials of disease-modifying treatments for PP MS are discussed, including immunosuppressants, immunomodulators, monoclonal antibodies, and putative neuroprotective agents...
November 4, 2016: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27804858/heat-shock-proteins-old-and-novel-roles-in-neurodegenerative-diseases-in-the-central-nervous-system
#9
Sandra Amor, Marianna Bugiani, Johannes M van Noort
Heat shock proteins (HSPs) are families of molecular chaperones that play important homeostatic functions in the central nervous system (CNS) by preventing protein misfolding, promoting degradation of improperly folded proteins, and protecting against apoptosis and inflammatory damage especially during hyperthermia, hypoxia, or oxidative stress. Under stress conditions, HSPs are upregulated to protect cells from damage that accumulates during ageing as well as pathological conditions. An important, yet frequently overlooked function of some HSPs is their ability to function as extracellular messengers (also termed chaperokines) that modulate immune responses within the CNS...
October 31, 2016: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/27797962/melanocortin-1-receptor-activation-is-neuroprotective-in-mouse-models-of-neuroinflammatory-disease
#10
Nadine Mykicki, Alexander M Herrmann, Nicholas Schwab, René Deenen, Tim Sparwasser, Andreas Limmer, Lydia Wachsmuth, Luisa Klotz, Karl Köhrer, Cornelius Faber, Heinz Wiendl, Thomas A Luger, Sven G Meuth, Karin Loser
In inflammation-associated progressive neuroinflammatory disorders, such as multiple sclerosis (MS), inflammatory infiltrates containing T helper 1 (TH1) and TH17 cells cause demyelination and neuronal degeneration. Regulatory T cells (Treg) control the activation and infiltration of autoreactive T cells into the central nervous system (CNS). In MS and experimental autoimmune encephalomyelitis (EAE) in mice, Treg function is impaired. We show that a recently approved drug, Nle(4)-d-Phe(7)-α-melanocyte-stimulating hormone (NDP-MSH), induced functional Treg, resulting in amelioration of EAE progression in mice...
October 26, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27794524/progressive-multiple-sclerosis-from-pathogenic-mechanisms-to-treatment
#11
Jorge Correale, María I Gaitán, María C Ysrraelit, Marcela P Fiol
During the past decades, better understanding of relapsing-remitting multiple sclerosis disease mechanisms have led to the development of several disease-modifying therapies, reducing relapse rates and severity, through immune system modulation or suppression. In contrast, current therapeutic options for progressive multiple sclerosis remain comparatively disappointing and challenging. One possible explanation is a lack of understanding of pathogenic mechanisms driving progressive multiple sclerosis. Furthermore, diagnosis is usually retrospective, based on history of gradual neurological worsening with or without occasional relapses, minor remissions or plateaus...
October 29, 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27774592/rifampicin-attenuates-experimental-autoimmune-encephalomyelitis-by-inhibiting-pathogenic-th17-cells-responses
#12
Ke Ma, Xi Chen, Jia-Cheng Chen, Ying Wang, Xi-Meng Zhang, Fan Huang, Jun-Jiong Zheng, Xiong Chen, Wei Yu, Ke-Ling Cheng, Yan-Qing Feng, Huai-Yu Gu
Rifampicin, a broad-spectrum antibiotic, has neuroprotective, immunosuppressive, and anti-inflammatory properties. However, the effect of rifampicin on autoimmune disorders of the nervous system is not clear. In this study, we investigated whether rifampicin was beneficial to myelin oligodendrocyte glycoprotein peptide (MOG33-35 )-induced female C57BL/6 experimental autoimmune encephalomyelitis (EAE) mice, the well-established animal model of multiple sclerosis. Rifampicin treatment (daily from the first day after EAE immunization) remarkably attenuated clinical signs and loss of body weight, which are associated with suppression of inflammatory infiltration and demyelination in spinal cords of EAE mice...
October 23, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27771018/bedside-to-bench-to-bedside-research-estrogen-receptor-beta-ligand-as-a-candidate-neuroprotective-treatment-for-multiple-sclerosis
#13
Noriko Itoh, Roy Kim, Mavis Peng, Emma DiFilippo, Hadley Johnsonbaugh, Allan MacKenzie-Graham, Rhonda R Voskuhl
Protective effects of pregnancy during MS have led to clinical trials of estriol, the pregnancy estrogen, in MS. Since estriol binds to estrogen receptor (ER) beta, ER beta ligand could represent a "next generation estriol" treatment. Here, ER beta ligand treatment was protective in EAE in both sexes and across genetic backgrounds. Neuroprotection was shown in spinal cord, sparing myelin and axons, and in brain, sparing neurons and synapses. Longitudinal in vivo MRIs showed decreased brain atrophy in cerebral cortex gray matter and cerebellum during EAE...
October 3, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27737733/conditioned-medium-of-periodontal-ligament-mesenchymal-stem-cells-exert-anti-inflammatory-effects-in-lipopolysaccharide-activated-mouse-motoneurons
#14
Thangavelu Soundara Rajan, Sabrina Giacoppo, Oriana Trubiani, Francesca Diomede, Adriano Piattelli, Placido Bramanti, Emanuela Mazzon
Conditioned medium derived from mesenchymal stem cells (MSCs) shows immunomodulatory and neuroprotective effects in preclinical models. Given the difficulty to harvest MSCs from bone marrow and adipose tissues, research has been focused to find alternative resources for MSCs, such as oral-derived tissues. Recently, we have demonstrated the protective effects of MSCs obtained from healthy human periodontal ligament tissue (hPDLSCs) in murine experimental autoimmune encephalomyelitis model. In the present in vitro study, we have investigated the immunomodulatory and neuroprotective effects of conditioned medium obtained from hPDLSCs of Relapsing Remitting- Multiple sclerosis (RR-MS) patients on NSC34 mouse motoneurons stimulated with lipopolysaccharide (LPS)...
October 11, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27733178/fumarate-modulates-the-immune-inflammatory-response-and-rescues-nerve-cells-and-neurological-function-after-stroke-in-rats
#15
Ruihe Lin, Jingli Cai, Eric W Kostuk, Robert Rosenwasser, Lorraine Iacovitti
BACKGROUND: Dimethyl fumarate (DMF), working via its metabolite monomethylfumarate (MMF), acts as a potent antioxidant and immunomodulator in animal models of neurologic disease and in patients with multiple sclerosis. These properties and their translational potential led us to investigate whether DMF/MMF could also protect at-risk and/or dying neurons in models of ischemic stroke in vitro and in vivo. Although the antioxidant effects have been partially addressed, the benefits of DMF immunomodulation after ischemic stroke still need to be explored...
October 13, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27725120/methylene-blue-alleviates-experimental-autoimmune-encephalomyelitis-by-modulating-ampk-sirt1-signaling-pathway-and-th17-treg-immune-response
#16
Jueqiong Wang, Congying Zhao, Peng Kong, Guanyun Bian, Zhe Sun, Yafei Sun, Li Guo, Bin Li
Methylene blue (MB) is an effective neuroprotectant in many neurological disorders. AMP-activated protein kinase (AMPK)/silent mating-type information regulation 2 homolog 1 (SIRT1) plays a crucial role in maintaining inflammatory responses and shows a synergistic effect on cell homeostasis. We investigated the effect of MB on experimental autoimmune encephalomyelitis (EAE), a classical animal model of multiple sclerosis (MS). MB treatment reduced the clinical scores of EAE significantly and attenuated pathological injuries in spinal cords...
October 15, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27725112/gene-expression-profiling-of-the-astrocyte-transcriptome-in-multiple-sclerosis-normal-appearing-white-matter-reveals-a-neuroprotective-role
#17
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
https://www.readbyqxmd.com/read/27721584/the-three-sisters-of-fate-in-multiple-sclerosis-klotho-clotho-fibroblast-growth-factor-23-lachesis-and-vitamin-d-atropos
#18
Hamit Yasar Ellidag, Necat Yilmaz, Fatma Kurtulus, Ozgur Aydin, Esin Eren, Ayca Inci, Suleyman Dolu, Fatma Demet Arslan Ince, Özlem Giray, Aylin Yaman
BACKGROUND: The klotho (Klt)-fibroblast growth factor-23 (FGF-23)-vitamin D axis is the main component of calcium (Ca) and phosphorus (P) metabolisms; on the contrary, it is also secreted from the choroid plexus (CP). PURPOSE: This study is aimed at evaluating serum soluble Klt (sKlt), FGF-23, and 25-(OH)-vitamin D levels in multiple sclerosis (MS) patients. METHODS: Thirty-two relapsing-remitting MS patients (11 males and 21 females; mean age 38...
September 2016: Annals of Neurosciences
https://www.readbyqxmd.com/read/27634580/fingolimod-enhances-myelin-repair-of-hippocampus-in-pentylenetetrazol-induced-kindling-model
#19
Mohammad Gol, Davoud Ghorbanian, Samaneh Hassanzadeh, Mohammad Javan, Javad Mirnajafi-Zadeh, Maryam Ghasemi-Kasman
Recent evidence indicates that demyelination occurs in epilepsy patients and kindling animal models. Regarding the well-known literature on anti-inflammatory and myelin protective effects of fingolimod (FTY720) in multiple sclerosis patients and animal models, we hypostatized whether FTY720 administration could exert myelin protective effects in pentylenetetrazol (PTZ)-induced kindling model. To end this, animals received 0.3 or 1mg/kg dosage of FTY720, 1h before PTZ injections. In another approach, after achieving fully kindling stage, FTY720 was administrated i...
September 12, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27625006/vertebral-hemangiomas-in-the-thoracic-spine-of-multiple-sclerosis-patients-are-connected-with-fewer-demyelinating-lesions-at-the-same-level-possible-impact-on-pathophysiology-and-clinical-course
#20
Maria Anagnostouli, Serafeim Katsavos, Andreas Kyrozis, Maria Gontika, Konstantinos I Voumvourakis, Elisabeth Kapaki
OBJECTIVES: Mechanisms of angiogenesis regulate multiple sclerosis (MS) lesions' evolution, displaying both neuroprotective and harmful effects. Factors traditionally considered as purely angiogenic, like vascular endothelial growth factor (VEGF), exert complex heterogenous actions on both neural and vascular malformation-derived tissues. Aim of this retrospective study was to examine, for the first time, potential associations between the presence of common vascular malformations, like vertebral hemangiomas (VHs), and several clinico-radiological MS parameters...
August 2016: Neurological Research
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