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Neuroprotection in multiple sclerosis

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
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
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
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
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
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
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
Lamia Mouhid Al-Achbili, Ana J Moreno-Ortega, Jorge Matías-Guiu, María F Cano-Abad, Ana Ruiz-Nuño
Therapeutic options for amyotrophic lateral sclerosis (ALS) are scarce and controversial. Although the aetiology of neuronal vulnerability is unknown, growing evidence supports a complex network in which multiple toxicity pathways, rather than a single mechanism, are involved in the pathogenesis of ALS. However, most cellular models only explain single pathogenic mechanisms. The present study proposes the two main cytotoxic mechanisms: (1) veratridine (VTD), which induced Na(+) and Ca(2+) overload; and (2) the TARD DNA-binding protein 43 (TDP-43) in NSC-34 cell line as an in vitro model of ALS...
October 28, 2016: Neuroscience Letters
Mariana Rinaldi, Laura Thomas, Patricia Mathieu, Pablo Carabias, Maria F Troncoso, Juana M Pasquini, Gabriel A Rabinovich, Laura A Pasquini
Galectin-1 (Gal-1), a member of a highly conserved family of animal lectins, binds to the common disaccharide [Galβ(1-4)-GlcNAc] on both N- and O-glycans decorating cell surface glycoconjugates. Current evidence supports a role for Gal-1 in the pathophysiology of multiple sclerosis (MS), one of the most prevalent chronic inflammatory diseases. Previous studies showed that Gal-1 exerts neuroprotective effects by promoting microglial deactivation in a model of autoimmune neuroinflammation and induces axonal regeneration in spinal cord injury...
September 6, 2016: Neurobiology of Disease
Julius O Enoru, Barbara Yang, Sesha Krishnamachari, Ernesto Villanueva, William DeMaio, Adiba Watanyar, Ramesh Chinnasamy, Jeffrey B Arterburn, Ruth G Perez
Parkinson's disease (PD) is a neurodegenerative aging disorder in which postmortem PD brain exhibits neuroinflammation, as well as synucleinopathy-associated protein phosphatase 2A (PP2A) enzymatic activity loss. Based on our translational research, we began evaluating the PD-repurposing-potential of an anti-inflammatory, neuroprotective, and PP2A stimulatory oral drug that is FDA-approved for multiple sclerosis, FTY720 (fingolimod, Gilenya®). We also designed two new FTY720 analogues, FTY720-C2 and FTY720-Mitoxy, with modifications that affect drug potency and mitochondrial localization, respectively...
2016: PloS One
Harika Dasari, Bharath Wootla, Arthur E Warrington, Moses Rodriguez
We provide an overview of rehabilitation in neurological diseases. A large amount of literature available on neurorehabilitation is based from the rehabilitative work on stroke and spinal cord injuries. After a brief description of rehabilitation, the potential application of neurorehabilitation in neurodegenerative diseases specifically multiple sclerosis (MS) is summarized. Since MS causes a wide variety of symptoms, the rehabilitation in MS patients may benefit from an interdisciplinary approach that encloses physiotherapy, cognitive rehabilitation, psychological therapy, occupational therapy, and other methods to improve fatigue...
August 2016: International Journal of Physical Medicine & Rehabilitation
Christiane Reick, Gisa Ellrichmann, Teresa Tsai, De-Hyung Lee, Stefan Wiese, Ralf Gold, Carsten Saft, Ralf A Linker
Glatiramer acetate (GA) is a FDA-approved drug which is licensed for the treatment of relapsing-remitting multiple sclerosis and which may exert neuroprotective effects via brain-derived neurotrophic factor (BDNF). In this study, we investigate effects of GA on BDNF expression especially in astrocytes in vitro and in vivo in brains of R6/2 and YAC128 transgenic mouse models of Huntington's disease (HD) where a pathogenic role of astroglial cells has recently been shown. We show that GA increases the expression of functionally active BDNF in astrocyte culture and in astrocytes of GA treated HD mice...
November 2016: Experimental Neurology
Jing-Wen Yu, Yan-Hua Li, Guo-Bin Song, Jie-Zhong Yu, Chun-Yun Liu, Jian-Chun Liu, Hai-Fei Zhang, Wan-Fang Yang, Qing Wang, Ya-Ping Yan, Bao-Guo Xiao, Cun-Gen Ma
Bone marrow-derived mesenchymal stem cells (MSCs) are the ideal transplanted cells of cellular therapy for promoting neuroprotection and neurorestoration. However, the optimization of transplanted cells and the improvement of microenvironment around implanted cells are still two critical challenges for enhancing therapeutic effect. In the current study, we observed the therapeutic potential of MSCs combined with Fasudil in mouse model of experimental autoimmune encephalomyelitis (EAE) and explored possible mechanisms of action...
August 30, 2016: Journal of Molecular Neuroscience: MN
Antonietta Gentile, Alessandra Musella, Silvia Bullitta, Diego Fresegna, Francesca De Vito, Roberta Fantozzi, Eleonora Piras, Francesca Gargano, Giovanna Borsellino, Luca Battistini, Anna Schubart, Georgia Mandolesi, Diego Centonze
BACKGROUND: Data from multiple sclerosis (MS) and the MS rodent model, experimental autoimmune encephalomyelitis (EAE), highlighted an inflammation-dependent synaptopathy at the basis of the neurodegenerative damage causing irreversible disability in these disorders. This synaptopathy is characterized by an imbalance between glutamatergic and GABAergic transmission and has been proposed to be a potential therapeutic target. Siponimod (BAF312), a selective sphingosine 1-phosphate1,5 receptor modulator, is currently under investigation in a clinical trial in secondary progressive MS patients...
2016: Journal of Neuroinflammation
Jie Wen, Prasanth S Ariyannur, Rachel Ribeiro, Mikiei Tanaka, John R Moffett, Batool F Kirmani, Aryan M A Namboodiri, Yumin Zhang
Melatonin and N-acetylserotonin (NAS) are tryptophan metabolites that have potent anti-oxidant, anti-inflammatory and neuroprotective properties in several animal models of neurological injury and disease including multiple sclerosis (MS). The therapeutic effect of NAS has not been reported previously in experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of MS. Using a MOG-peptide induced EAE mouse model we examined the effects of melatonin and NAS on clinical score, inflammatory markers, free radical generation, and sparing of axons, oligodendrocytes and myelin...
August 25, 2016: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Sinoy Sugunan, Sreekala S Nampoothiri, Tanya Garg, Rajanikant G Krishnamurthy
KCa3.1 protein is part of a heterotetrameric voltage-independent potassium channel, the activity of which depends on the intracellular calcium binding to calmodulin. KCa3.1 is immensely significant in regulating immune responses and primarily expressed in cells of hematopoietic lineage. It is one of the attractive pharmacological targets that are known to inhibit neuroinflammation. KCa3.1 blockers mediate neuroprotection through multiple mechanisms, such as by targeting microglia-mediated neuronal killing. KCa3...
August 22, 2016: CNS & Neurological Disorders Drug Targets
Yaoming Wang, Zhen Zhao, Sanket V Rege, Min Wang, Gabriel Si, Yi Zhou, Su Wang, John H Griffin, Steven A Goldman, Berislav V Zlokovic
Activated protein C (APC) is a blood protease with anticoagulant activity and cell-signaling activities mediated by the activation of protease-activated receptor 1 (F2R, also known as PAR1) and F2RL1 (also known as PAR3) via noncanonical cleavage. Recombinant variants of APC, such as the 3K3A-APC (Lys191-193Ala) mutant in which three Lys residues (KKK191-193) were replaced with alanine, and/or its other mutants with reduced (>90%) anticoagulant activity, engineered to reduce APC-associated bleeding risk while retaining normal cell-signaling activity, have shown benefits in preclinical models of ischemic stroke, brain trauma, multiple sclerosis, amyotrophic lateral sclerosis, sepsis, ischemic and reperfusion injury of heart, kidney and liver, pulmonary, kidney and gastrointestinal inflammation, diabetes and lethal body radiation...
September 2016: Nature Medicine
Jing-Jing Wang, Tian-Le Xu
Protons are widespread in cells and serve a variety of important functions. In certain pathological conditions, acid-base balance was disrupted and therefore excessive protons were generated and accumulated, which is termed acidosis and proved toxic to the organism. In the nervous system, it has been reported that acidosis was a common phenomenon and contributed to neuronal injury in various kinds of neurological diseases, such as ischemic stroke, multiple sclerosis and Huntington's disease. Acid-sensing ion channels (ASICs) is the key receptor of protons and mediates acidosis-induced neuronal injury, but the underlying mechanism remains unclear...
August 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Michael D Lovelace, Bianca Varney, Gayathri Sundaram, Nunzio F Franco, Mei Li Ng, Saparna Pai, Chai K Lim, Gilles J Guillemin, Bruce J Brew
The kynurenine pathway (KP) is the major metabolic pathway of the essential amino acid tryptophan (TRP). Stimulation by inflammatory molecules, such as interferon-γ (IFN-γ), is the trigger for induction of the KP, driving a complex cascade of production of both neuroprotective and neurotoxic metabolites, and in turn, regulation of the immune response and responses of brain cells to the KP metabolites. Consequently, substantial evidence has accumulated over the past couple of decades that dysregulation of the KP and the production of neurotoxic metabolites are associated with many neuroinflammatory and neurodegenerative diseases, including Parkinson's disease, AIDS-related dementia, motor neurone disease, schizophrenia, Huntington's disease, and brain cancers...
2016: Frontiers in Immunology
Mualla Hamurcu, Gürdal Orhan, Murat Sinan Sarıcaoğlu, Semra Mungan, Zeynep Duru
We aimed to analyze the effects of progressive myelin loss and neurodegeneration seen in patients with multiple sclerosis (MS) on visual tract with electrophysiological and structural tests. Fifty-one patients diagnosed with MS in the Neurology Department were followed up in neuro-ophthalmology outpatient clinic irrespective of their visual symptoms, and were included in our study. The patients were classified as the ones with the history of optic neuritis (group II) and ones without the history (group I) of optic neuritis...
August 18, 2016: International Ophthalmology
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