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Neuroprotection in multiple sclerosis

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https://www.readbyqxmd.com/read/28817212/fingolimod-against-endotoxin-induced-fetal-brain-injury-in-a-rat-model
#1
And Yavuz, Mekin Sezik, Ozlem Ozmen, Halil Asci
AIM: Fingolimod is a sphingosine-1-phosphate receptor modulator used for multiple sclerosis treatment and acts on cellular processes such as apoptosis, endothelial permeability, and inflammation. We hypothesized that fingolimod has a positive effect on alleviating preterm fetal brain injury. METHODS: Sixteen pregnant rats were divided into four groups of four rats each. On gestational day 17, i.p. endotoxin was injected to induce fetal brain injury, followed by i...
August 17, 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28805746/melanocortins-melanocortin-receptors-and-multiple-sclerosis
#2
REVIEW
Robert P Lisak, Joyce A Benjamins
The melanocortins and their receptors have been extensively investigated for their roles in the hypothalamo-pituitary-adrenal axis, but to a lesser extent in immune cells and in the nervous system outside the hypothalamic axis. This review discusses corticosteroid dependent and independent effects of melanocortins on the peripheral immune system, central nervous system (CNS) effects mediated through neuronal regulation of immune system function, and direct effects on endogenous cells in the CNS. We have focused on the expression and function of melanocortin receptors in oligodendroglia (OL), the myelin producing cells of the CNS, with the goal of identifying new therapeutic approaches to decrease CNS damage in multiple sclerosis as well as to promote repair...
August 14, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28795301/organotypic-cultures-from-the-adult-cns-a-novel-model-to-study-demyelination-and-remyelination-ex-vivo
#3
Glaiza A Tan, Kendra L Furber, Merlin P Thangaraj, LaRhonda Sobchishin, J Ronald Doucette, Adil J Nazarali
Experimental models of multiple sclerosis (MS) have significantly advanced our understanding of pathophysiology and therapeutic interventions. Although in vivo rodent models are considered to most closely represent the complex cellular and molecular disease states of the human central nervous system (CNS), these can be costly to maintain and require long timelines. Organotypic slice cultures maintain the cytotypic organization observed in the intact CNS, yet provide many of the experimental advantages of in vitro cell culture models...
August 9, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28783872/evaluation-of-potential-drug-drug-interaction-between-delayed-release-dimethyl-fumarate-and-a-commonly-used-oral-contraceptive-norgestimate-ethinyl-estradiol-in-healthy-women
#4
Bing Zhu, Ivan Nestorov, Guolin Zhao, Venkata Meka, Mark Leahy, Jeanelle Kam, Sarah I Sheikh
Delayed-release dimethyl fumarate (DMF) is an oral therapy for relapsing multiple sclerosis with anti-inflammatory and neuroprotective properties. This 2-period crossover study was conducted to evaluate the potential for drug-drug interaction between DMF (240 mg twice daily) and a combined oral contraceptive (OC; norgestimate 250 μg, ethinyl estradiol 35 μg). Forty-six healthy women were enrolled; 32 completed the study. After the lead-in period (OC alone), 41 eligible participants were randomized 1:1 to sequence 1 (OC and DMF coadministration in period 1; OC alone in period 2) or sequence 2 (regimens reversed)...
August 7, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28776122/mechanisms-involved-in-the-remyelinating-effect-of-sildenafil
#5
Daniela Díaz-Lucena, María Gutierrez-Mecinas, Beatriz Moreno, José Lupicinio Martínez-Sánchez, Paula Pifarré, Agustina García
Remyelination occurs in demyelinated lesions in multiple sclerosis (MS) and pharmacological treatments that enhance this process will critically impact the long term functional outcome in the disease. Sildenafil, a cyclic GMP (cGMP)-specific phosphodiesterase 5 inhibitor (PDE5-I), is an oral vasodilator drug extensively used in humans for treatment of erectile dysfunction and pulmonary arterial hypertension. PDE5 is expressed in central nervous system (CNS) neuronal and glial populations and in endothelial cells and numerous studies in rodent models of neurological disease have evidenced the neuroprotective potential of PDE5-Is...
August 3, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28770481/the-role-of-advanced-magnetic-resonance-imaging-techniques-in-multiple-sclerosis-clinical-trials
#6
REVIEW
Kedar R Mahajan, Daniel Ontaneda
Magnetic resonance imaging has been crucial in the development of anti-inflammatory disease-modifying treatments. The current landscape of multiple sclerosis clinical trials is currently expanding to include testing not only of anti-inflammatory agents, but also neuroprotective, remyelinating, neuromodulating, and restorative therapies. This is especially true of therapies targeting progressive forms of the disease where neurodegeneration is a prominent feature. Imaging techniques of the brain and spinal cord have rapidly evolved in the last decade to permit in vivo characterization of tissue microstructural changes, connectivity, metabolic changes, neuronal loss, glial activity, and demyelination...
August 2, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28759648/anemoside-a3-ameliorates-experimental-autoimmune-encephalomyelitis-by-modulating-t-helper-17-cell-response
#7
Fanny C F Ip, Yu Pong Ng, Terry C T Or, Peiran Sun, Guangmiao Fu, Jessica Y H Li, Wen-Cai Ye, Tom H Cheung, Nancy Y Ip
Anemoside A3 (AA3) is a natural triterpenoid glycoside isolated from the root of Pulsatilla chinensis (Bunge) Regel. We previously showed that AA3 exhibits cognitive-enhancing and neuroprotective properties. In the present study, we demonstrated that AA3 modulates inflammatory responses by regulating prostaglandin E receptor 4 signaling. Because prostaglandin E receptor 4 is involved in the pathophysiology of experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), we assessed the beneficial effect of AA3 in EAE mice...
2017: PloS One
https://www.readbyqxmd.com/read/28752800/can-resistance-training-impact-mri-outcomes-in-relapsing-remitting-multiple-sclerosis
#8
Tue Kjølhede, Susanne Siemonsen, Damian Wenzel, Jan-Patrick Stellmann, Steffen Ringgaard, Bodil Ginnerup Pedersen, Egon Stenager, Thor Petersen, Kristian Vissing, Christoph Heesen, Ulrik Dalgas
BACKGROUND: Multiple sclerosis (MS) is characterised by accelerated brain atrophy, which relates to disease progression. Previous research shows that progressive resistance training (PRT) can counteract brain atrophy in other populations. OBJECTIVE: To evaluate the effects of PRT by magnetic resonance imaging (MRI) and clinical measures of disease progression in people with MS. METHODS: This study was a 24-week randomised controlled cross-over trial, including a Training ( n = 18, 24 weeks of PRT followed by self-guided physical activity) and Waitlist group ( n = 17, 24 weeks of habitual lifestyle followed by PRT)...
July 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28738875/effects-of-fty720-on-brain-neurogenic-niches-in-vitro-and-after-kainic-acid-induced-injury
#9
Raffaela Cipriani, Juan Carlos Chara, Alfredo Rodríguez-Antigüedad, Carlos Matute
BACKGROUND: FTY720 (fingolimod, Gilenya™) is an oral, blood-brain barrier (BBB)-passing drug approved as immunomodulatory treatment for relapsing-remitting form of the multiple sclerosis (MS). In addition, FTY720 exerts several effects in the central nervous system (CNS), ranging from neuroprotection to reduction of neuroinflammation. However, the neurogenic and oligodendrogenic potential of FTY720 has been poorly investigated. In this study, we assessed the effect of FTY720 on the production of new neurons and oligodendrocytes from neural stem/precursor cells both in vitro and in vivo...
July 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28726788/neuroprotection-by-eif2%C3%AE-chop-inhibition-and-xbp-1-activation-in-eae-optic-neuritiss
#10
Haoliang Huang, Linqing Miao, Feisi Liang, Xiaodong Liu, Lin Xu, Xiuyin Teng, Qizhao Wang, William H Ridder, Kenneth S Shindler, Yang Sun, Yang Hu
No therapies exist to prevent neuronal deficits in multiple sclerosis (MS), because the molecular mechanism responsible for the progressive neurodegeneration is unknown. We previously showed that axon injury-induced neuronal endoplasmic reticulum (ER) stress plays an important role in retinal ganglion cell (RGC) death and optic nerve degeneration in traumatic and glaucomatous optic neuropathies. Optic neuritis, one of the most common clinical manifestations of MS, is readily modeled by experimental autoimmune encephalomyelitis (EAE) in mouse...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28702353/longitudinal-mr-spectroscopy-of-neurodegeneration-in-multiple-sclerosis-with-diffusion-of-the-intra-axonal-constituent-n-acetylaspartate
#11
Emily Turner Wood, Ece Ercan, Pascal Sati, Irene C M Cortese, Itamar Ronen, Daniel S Reich
Multiple sclerosis (MS) is a pathologically complex CNS disease: inflammation, demyelination, and neuroaxonal degeneration occur concurrently and may depend on one another. Current therapies are aimed at the immune-mediated, inflammatory destruction of myelin, whereas axonal degeneration is ongoing and not specifically targeted. Diffusion-weighted magnetic resonance spectroscopy can measure the diffusivity of metabolites in vivo, such as the axonal/neuronal constituent N-acetylaspartate, allowing compartment-specific assessment of disease-related changes...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28697282/exploring-the-potential-of-natural-and-synthetic-neuroprotective-steroids-against-neurodegenerative-disorders-a-literature-review
#12
REVIEW
Ranju Bansal, Ranjit Singh
Neurodegeneration is a complex process, which leads to progressive brain damage due to loss of neurons. Despite exhaustive research, the cause of neuronal loss in various degenerative disorders is not entirely understood. Neuroprotective steroids constitute an important line of attack, which could play a major role against the common mechanisms associated with various neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Natural endogenous steroids induce the neuroprotection by protecting the nerve cells from neuronal injury through multiple mechanisms, therefore the structural modifications of the endogenous steroids could be helpful in the generation of new therapeutically useful neuroprotective agents...
July 11, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28694434/laquinimod-treatment-in-the-r6-2-mouse-model
#13
Gisa Ellrichmann, Alina Blusch, Oluwaseun Fatoba, Janine Brunner, Liat Hayardeny, Michael Hayden, Dominik Sehr, Konstanze F Winklhofer, Carsten Saft, Ralf Gold
The transgenic mouse model R6/2 exhibits Huntington's disease (HD)-like deficits and basic pathophysiological similarities. We also used the pheochromocytoma-12 (PC12)-cell-line-model to investigate the effect of laquinimod on metabolic activity. Laquinimod is an orally administered immunomodulatory substance currently under development for the treatment of multiple sclerosis (MS) and HD. As an essential effect, increased levels of BDNF were observed. Therefore, we investigated the therapeutic efficacy of laquinimod in the R6/2 model, focusing on its neuroprotective capacity...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28680531/mitochondrial-uncoupler-prodrug-of-2-4-dinitrophenol-mp201-prevents-neuronal-damage-and-preserves-vision-in-experimental-optic-neuritis
#14
Reas S Khan, Kimberly Dine, John G Geisler, Kenneth S Shindler
The ability of novel mitochondrial uncoupler prodrug of 2,4-dinitrophenol (DNP), MP201, to prevent neuronal damage and preserve visual function in an experimental autoimmune encephalomyelitis (EAE) model of optic neuritis was evaluated. Optic nerve inflammation, demyelination, and axonal loss are prominent features of optic neuritis, an inflammatory optic neuropathy often associated with the central nervous system demyelinating disease multiple sclerosis. Currently, optic neuritis is frequently treated with high-dose corticosteroids, but treatment fails to prevent permanent neuronal damage and associated vision changes that occur as optic neuritis resolves, thus suggesting that additional therapies are required...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28677678/srsf1-dependent-nuclear-export-inhibition-of-c9orf72-repeat-transcripts-prevents-neurodegeneration-and-associated-motor-deficits
#15
Guillaume M Hautbergue, Lydia M Castelli, Laura Ferraiuolo, Alvaro Sanchez-Martinez, Johnathan Cooper-Knock, Adrian Higginbottom, Ya-Hui Lin, Claudia S Bauer, Jennifer E Dodd, Monika A Myszczynska, Sarah M Alam, Pierre Garneret, Jayanth S Chandran, Evangelia Karyka, Matthew J Stopford, Emma F Smith, Janine Kirby, Kathrin Meyer, Brian K Kaspar, Adrian M Isaacs, Sherif F El-Khamisy, Kurt J De Vos, Ke Ning, Mimoun Azzouz, Alexander J Whitworth, Pamela J Shaw
Hexanucleotide repeat expansions in the C9ORF72 gene are the commonest known genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Expression of repeat transcripts and dipeptide repeat proteins trigger multiple mechanisms of neurotoxicity. How repeat transcripts get exported from the nucleus is unknown. Here, we show that depletion of the nuclear export adaptor SRSF1 prevents neurodegeneration and locomotor deficits in a Drosophila model of C9ORF72-related disease. This intervention suppresses cell death of patient-derived motor neuron and astrocytic-mediated neurotoxicity in co-culture assays...
July 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28676349/immunoregulatory-effect-of-mast-cells-influenced-by-microbes-in-neurodegenerative-diseases
#16
Francesco Girolamo, Cristiana Coppola, Domenico Ribatti
When related to central nervous system (CNS) health and disease, brain mast cells (MCs) can be a source of either beneficial or deleterious signals acting on neural cells. We review the current state of knowledge about molecular interactions between MCs and glia in neurodegenerative diseases such as Multiple Sclerosis, Alzheimer's disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, Epilepsy. We also discuss the influence on MC actions evoked by the host microbiota, which has a profound effect on the host immune system, inducing important consequences in neurodegenerative disorders...
July 1, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28675779/neurosteroidogenesis-and-progesterone-anti-inflammatory-neuroprotective-effects
#17
REVIEW
Alejandro F De Nicola, Laura I Garay, Maria Meyer, Rachida Guennoun, Regine Sitruk-Ware, Michael Schumacher, Maria Claudia Gonzalez Deniselle
Progesterone shows anti-inflammatory and promyelinating effects in mice with autoimmune experimental encephalomyelitis (EAE), a commonly used model for multiple sclerosis (MS). Since neurosteroids have been implicated as protective factors for MS and EAE, we analyzed the expression of neurosteroidogenic enzymes in the compromised spinal cord of EAE mice. EAE was induced in female C57Bl6 mice and killed on day 16 after induction. Progesterone was given by pellet implantation 1 week before EAE induction. Untreated EAE mice showed decreased mRNAs for the steroidogenic acute regulatory protein (Star), voltage-dependent anion channel (VDAC), cholesterol side-chain cleavage (P450scc), 5α-reductase, 3α-hydroxysteroid dehydrogenase (3α-HSOR) and aromatase, whereas changes of 3β-hydroxysteroid dehydrogenase (3β-HSD) were not significant...
July 4, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28675259/review-of-the-novelties-from-the-32nd-ectrims-congress-2016-presented-at-the-9th-post-ectrims-meeting-ii
#18
REVIEW
O Fernandez, A Oterino, C Oreja-Guevara, J M Prieto, M M Mendibe-Bilbao, J A Garcia-Merino, Ll Ramio-Torrenta, R Ginestal, J E Meca-Lallana, L Romero-Pinel, D Munoz, P Oliva-Nacarino, M C Calles-Hernandez, G Izquierdo, M L Martinez-Gines, A Saiz, M Comabella, B Casanova-Estruch, Ll Brieva, R Arroyo, A Rodriguez-Antiguedad
For the ninth year in a row the Post-ECTRIMS Meeting has been held in Madrid (Spain) with the aim of presenting and discussing the hottest issues debated at the ECTRIMS Congress by renowned specialists in multiple sclerosis in our country. One outcome of this scientific activity, endorsed by the Spanish Neurology Society, is this review article, which is published in two parts. This second part reflects the current controversy over the management of multiple sclerosis, especially as regards the progressive forms and their differential diagnosis...
July 16, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28668079/effects-of-bu-shen-yi-sui-capsule-on-nogoa-ngr-and-its-signaling-pathways-rhoa-rock-in-mice-with-experimental-autoimmune-encephalomyelitis
#19
Ling Fang, Yongqiang Wang, Qi Zheng, Tao Yang, Peiyuan Zhao, Hui Zhao, Qiuxia Zhang, Yuanyuan Zhao, Fang Qi, Kangning Li, Zhenzhen Chen, Junling Li, Nan Zhang, Yongping Fan, Lei Wang
BACKGROUND: Axon growth inhibitory factors NogoA/Nogo receptor (NgR) and its signaling pathways RhoA/Rho kinase (ROCK) play a critical role in the repair of nerve damage in multiple sclerosis (MS). Bu Shen Yi Sui Capsule (BSYSC) is an effective Chinese formula utilized to treat MS in clinical setting and noted for its potent neuroprotective effects. In this study, we focus on the effects of BSYSC on promoting nerve repair and the underlying mechanisms in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS...
July 1, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28655617/the-effects-of-berberine-on-a-murine-model-of-multiple-sclerosis-and-the-sphk1-s1p-signaling-pathway
#20
Jiaming Luo, Rong Chen, Siyu Zeng, Juming Yu, Guohui Jiang, Li Wang, Xinyue Qin
Berberine (BBR) has shown neuroprotective properties. The present study aims to investigate the effects of BBR on experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), and SphK1/S1P signaling, which plays a key role in MS. EAE was induced in mice, followed by treatment with BBR at 50, 100, or 300 mg/kg/d. Neurophysiological function was evaluated daily; inflammation, cell infiltration, and the severity of demyelination were also examined. The SphK1, SphK2, and S1P levels in the animals and primary astrocyte culture were measured...
June 24, 2017: Biochemical and Biophysical Research Communications
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