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Neuroprotection in multiple sclerosis

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https://www.readbyqxmd.com/read/29228214/oestrogen-receptor-%C3%AE-ligand-acts-on-cd11c-cells-to-mediate-protection-in-experimental-autoimmune-encephalomyelitis
#1
Roy Y Kim, Darian Mangu, Alexandria S Hoffman, Rojan Kovash, Eunice Jung, Noriko Itoh, Rhonda Voskuhl
Oestrogen treatments are neuroprotective in a variety of neurodegenerative disease models. Selective oestrogen receptor modifiers are needed to optimize beneficial effects while minimizing adverse effects to achieve neuroprotection in chronic diseases. Oestrogen receptor beta (ERβ) ligands are potential candidates. In the multiple sclerosis model chronic experimental autoimmune encephalomyelitis, ERβ-ligand treatment is neuroprotective, but mechanisms underlying this neuroprotection remain unclear. Specifically, whether there are direct effects of ERβ-ligand on CD11c+ microglia, myeloid dendritic cells or macrophages in vivo during disease is unknown...
December 8, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29222803/synthesis-of-biocompatible-titanate-nanofibers-for-effective-delivery-of-neuroprotective-agents
#2
Asya Ozkizilcik, Roger Williams, Z Ryan Tian, Dafin F Muresanu, Aruna Sharma, Hari S Sharma
Nanoscience provides us with new opportunities to develop nanotechnologies for treating, in particular, central nervous system disorders such as Alzheimer disease and multiple sclerosis. From a methodological point of view, it is challenging to deliver drugs effectively across the blood-brain barrier and blood-cerebrospinal fluid barrier. Our 10-year data and reports from both in vivo and in vitro studies, however, have consistently proved that therapeutic drugs of different types can be generally loaded in/on the nanocarriers for targeted and programmable deliveries to the central nervous system with a high degree of efficacy...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29213032/-staging-of-neuroplasticity-alterations-during-epileptogenesis-temporal-lobe-epileply-as-an-example
#3
N V Gulyaeva
Using temporal lobe epilepsy as an example, staging of long term plasticity in the hippocampus is considered. Major stages demonstrating opposite alterations in neuroplasticity are active epileptogenesis and the period of established temporal lobe epilepsy. During the epileptogenesis, multiple events resulting in forming of epileptic neuronal nets occur: changes in glutamatergic and GABAergic neurons, increase of aberrant neurogenesis, axonal sprouting and dendrite remodeling, particularly, supported by an excessive enhancement of the BDNF system in specific hippocampal regions...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/29198015/the-anti-inflammatory-effects-of-4-5-bromo-3-chloro-2-hydroxybenzyl-amino-2-hydroxybenzoic-acid-in-lipopolysaccharide-activated-primary-microglial-cells
#4
Xiang Cao, Yuexinzi Jin, He Zhang, Linjie Yu, Xinyu Bao, Fei Li, Yun Xu
Over-activated microglial cells are known to be implicated in various neurological diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis. Our previous reports have shown that ZL006, a compound with a hydrophobic ring A and a hydrophilic ring B with a carboxyl group, exhibited stronger neuroprotective activity in vitro and in vivo. However, the directly anti-inflammatory effects of these compounds in the central nervous system (CNS) have not been elucidated. In the present study, as a part of our ongoing screening experiment to evaluate the anti-inflammatory effects of new compounds, a newly synthesized 4-((5-bromo-3-chloro-2-hydroxybenzyl) amino)-2-hydroxybenzoic acid (LX007) was used to examine whether it could reduce the inflammatory responses of activated microglia...
December 2, 2017: Inflammation
https://www.readbyqxmd.com/read/29197515/fingolimod-anti-inflammatory-and-neuroprotective-effects-modulation-of-rage-axis-in-multiple-sclerosis-patients
#5
Zohara Sternberg, Channa Kolb, Kailash Chadha, Adam Nir, Raphael Nir, Rayan George, Joseph Johnson, Jinhee Yu, David Hojnacki
BACKGROUND: We investigated Fingolimod treatment effects on the RAGE (receptor for advanced glycation endproducts) axis in multiple sclerosis (MS) patients. The primary outcome of the study was whether Fingolimod treatment increases serum levels of the soluble RAGE isoforms, sRAGE and esRAGE - both being considered putative endogenous inhibitors of RAGE signaling. Additional variables were serum levels of RAGE ligands, the high mobility group box (HMGB)1 and pentosidine. METHODS: Serum levels of the study variables were measured by ELISA, and compared between baseline (before Fingolimod treatment) and 6 and 12 months post-drug treatment in 17 relapsing MS patients...
November 29, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29172994/amiloride-does-not-protect-retinal-nerve-fibre-layer-thickness-in-optic-neuritis-in-a-phase-2-randomised-controlled-trial
#6
Justin B McKee, Charles L Cottriall, John Elston, Simon Epps, Nikos Evangelou, Stephen Gerry, Christopher Kennard, Yazhuo Kong, Abigail Koelewyn, Wilhelm Kueker, Maria Isabel Leite, Jacqueline Palace, Matthew Craner
BACKGROUND: Recent basic and clinical evidence suggests amiloride may be neuroprotective in multiple sclerosis (MS) through the blockade of the acid sensing ion channel (ASIC). OBJECTIVE: To examine the neuroprotective efficacy of amiloride in acute optic neuritis (ON). METHODS: A total of 48 patients were recruited to a phase 2, double blind, single site, randomised controlled trial. Scanning laser polarimetry (GDx) at 6 months was the primary outcome measure and optical coherence tomography (OCT) and visual and electrophysiological measures were secondary outcome measures...
November 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29157398/new-advances-in-disease-modifying-therapies-for-relapsing-and-progressive-forms-of-multiple-sclerosis
#7
REVIEW
Angela Vidal-Jordana
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system in which inflammation, demyelination, and axonal loss occurs from early stages of the disease. It mainly affects people between 20 and 40 years old, with a female predominance. Treatment options have been increasingly growing in the past years and newer drugs, some with novel mechanisms of action, are being developed for treating patients with MS. There is an increasing interest in developing new drugs that will promote neuroprotection and/or myelin repair through different mechanisms of action that may target the most degenerative component of the disease...
February 2018: Neurologic Clinics
https://www.readbyqxmd.com/read/29154076/multiple-intracerebroventricular-injections-of-human-umbilical-cord-mesenchymal-stem-cells-delay-motor-neurons-loss-but-not-disease-progression-of-sod1g93a-mice
#8
Francesca Sironi, Antonio Vallarola, Martina Bruna Violatto, Laura Talamini, Mattia Freschi, Roberta De Gioia, Chiara Capelli, Azzurra Agostini, Davide Moscatelli, Massimo Tortarolo, Paolo Bigini, Martino Introna, Caterina Bendotti
Stem cell therapy is considered a promising approach in the treatment of amyotrophic lateral sclerosis (ALS) and mesenchymal stem cells (MSCs) seem to be the most effective in ALS animal models. The umbilical cord (UC) is a source of highly proliferating fetal MSCs, more easily collectable than other MSCs. Recently we demonstrated that human (h) UC-MSCs, double labeled with fluorescent nanoparticles and Hoechst-33258 and transplanted intracerebroventricularly (ICV) into SOD1G93A transgenic mice, partially migrated into the spinal cord after a single injection...
November 10, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29150274/neuroprotective-potential-of-high-dose-biotin
#9
Mark F McCarty, James J DiNicolantonio
A recent controlled trial has established that high-dose biotin supplementation - 100 mg, three times daily - has a stabilizing effect on progression of multiple sclerosis (MS). Although this effect has been attributed to an optimization of biotin's essential cofactor role in the brain, a case can be made that direct stimulation of soluble guanylate cyclase (sGC) by pharmacological concentrations of biotin plays a key role in this regard. The utility of high-dose biotin in MS might reflect an anti-inflammatory effect of cGMP on the cerebral microvasculature, as well on oligodendrocyte differentiation and on Schwann cell production of neurotrophic factors thought to have potential for managing MS...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29138536/spotlight-on-siponimod-and-its-potential-in-the-treatment-of-secondary-progressive-multiple-sclerosis-the-evidence-to-date
#10
REVIEW
Alberto Gajofatto
Siponimod (BAF312) is a synthetic molecule belonging to the sphingosine-1-phosphate (S1P) modulator family, which has putative neuroprotective properties and well-characterized immunomodulating effects mediated by sequestration of B and T cells in secondary lymphoid organs. Compared to fingolimod (ie, precursor of the S1P modulators commercially available for the treatment of relapsing-remitting [RR] multiple sclerosis [MS]), siponimod exhibits selective affinity for types 1 and 5 S1P receptor, leading to a lower risk of adverse events that are mainly induced by S1P3 receptor activation, such as bradycardia and vasoconstriction...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29137141/steroid-and-xenobiotic-receptor-signalling-in-apoptosis-and-autophagy-of-the-nervous-system
#11
REVIEW
Agnieszka Wnuk, Małgorzata Kajta
Apoptosis and autophagy are involved in neural development and in the response of the nervous system to a variety of insults. Apoptosis is responsible for cell elimination, whereas autophagy can eliminate the cells or keep them alive, even in conditions lacking trophic factors. Therefore, both processes may function synergistically or antagonistically. Steroid and xenobiotic receptors are regulators of apoptosis and autophagy; however, their actions in various pathologies are complex. In general, the estrogen (ER), progesterone (PR), and mineralocorticoid (MR) receptors mediate anti-apoptotic signalling, whereas the androgen (AR) and glucocorticoid (GR) receptors participate in pro-apoptotic pathways...
November 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29128626/neuroprotective-and-neurotrophic-effects-of-lanthionine-ketimine-ester
#12
Natalia Marangoni, Kathy Kowal, Zane Deliu, Kenneth Hensley, Douglas L Feinstein
Lanthionine ketimine ethyl ester (LKE) is a synthetic derivative of the naturally occurring amino acid lanthionine ketimine. We previously showed that LKE reduced clinical signs in a mouse model of multiple sclerosis (MS) associated with reductions in axonal damage; however, whether LKE has direct beneficial actions on mammalian neuronal cells was not examined. In the current study, we tested the effects of LKE in SH-SY5Y human neuronal cells and in primary mouse cerebellar granule neurons. In both cell types, LKE dose-dependently reduced the cell death that occurred spontaneously followed a change in media...
November 8, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29123469/suppression-of-inflammatory-demyelinaton-and-axon-degeneration-through-inhibiting-kv3-channels
#13
Peter Jukkola, Yuanzheng Gu, Amy E Lovett-Racke, Chen Gu
The development of neuroprotective and repair strategies for treating progressive multiple sclerosis (MS) requires new insights into axonal injury. 4-aminopyridine (4-AP), a blocker of voltage-gated K(+) (Kv) channels, is used in symptomatic treatment of progressive MS, but the underlying mechanism remains unclear. Here we report that deleting Kv3.1-the channel with the highest 4-AP sensitivity-reduces clinical signs in experimental autoimmune encephalomyelitis (EAE), a mouse model for MS. In Kv3.1 knockout (KO) mice, EAE lesions in sensory and motor tracts of spinal cord were markedly reduced, and radial astroglia were activated with increased expression of brain derived neurotrophic factor (BDNF)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29114096/fingolimod-protects-against-ischemic-white-matter-damage-by-modulating-microglia-toward-m2-polarization-via-stat3-pathway
#14
Chuan Qin, Wen-Hui Fan, Qian Liu, Ke Shang, Madhuvika Murugan, Long-Jun Wu, Wei Wang, Dai-Shi Tian
BACKGROUND AND PURPOSE: White matter (WM) ischemic injury, a major neuropathological feature of cerebral small vessel diseases, is an important cause of vascular cognitive impairment in later life. The pathogenesis of demyelination after WM ischemic damage are often accompanied by microglial activation. Fingolimod (FTY720) was approved for the treatment of multiple sclerosis for its immunosuppression property. In this study, we evaluated the neuroprotective potential of FTY720 in a WM ischemia model...
November 7, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29101799/s-allyl-cysteine-improves-clinical-and-neuropathological-features-of-experimental-autoimmune-encephalomyelitis-in-c57bl-6-mice
#15
Hossein Zeinali, Tourandokht Baluchnejadmojarad, Soudabeh Fallah, Mohsen Sedighi, Nariman Moradi, Mehrdad Roghani
Multiple sclerosis (MS) is a deleterious autoimmune and demyelinating disorder of the central nervous system with debilitating sensory and motor complications. There is still no definite cure for it and the main focus for its treatment mostly pivots around subsiding its severity and recurrence. Experimental autoimmune encephalomyelitis (EAE) is an established animal model of MS. S-allyl cysteine (SAC) is the active and main constituent of aged garlic extract with anti-inflammatory and neuroprotective property...
November 1, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29097192/the-endocannabinoid-system-and-its-therapeutic-exploitation-in-multiple-sclerosis-clues-for-other-neuroinflammatory-diseases
#16
REVIEW
Valerio Chiurchiù, Mario van der Stelt, Diego Centonze, Mauro Maccarrone
Multiple sclerosis is the most common inflammatory demyelinating disease of the central nervous system, caused by an autoimmune response against myelin that eventually leads to progressive neurodegeneration and disability. Although the knowledge on its underlying neurobiological mechanisms has considerably improved, there is a still unmet need for new treatment options, especially for the progressive forms of the disease. Both preclinical and clinical data suggest that cannabinoids, derived from the Cannabis sativa plant, may be used to control symptoms such as spasticity and chronic pain, whereas only preclinical data indicate that these compounds and their endogenous counterparts, i...
October 31, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/29079885/therapeutic-potential-of-curcumin-for-multiple-sclerosis
#17
Munibah Qureshi, Ebtesam A Al-Suhaimi, Fazli Wahid, Omer Shehzad, Adeeb Shehzad
Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS), characterized by demyelination, neuronal injury, and breaching of the blood-brain barrier (BBB). Epidemiological studies have shown that immunological, genetic, and environmental factors contribute to the progression and development of MS. T helper 17 (Th17) cells are crucial immunological participant in the pathophysiology of MS. The aberrant production of IL-17 and IL-22 by Th17 cells crosses BBB promotes its disruption and interferes with transmission of nerve signals through activation of neuroinflammation in the CNS...
October 27, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/29057962/tnfr1-inhibition-with-a-nanobody-protects-against-eae-development-in-mice
#18
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
#19
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
#20
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
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