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Multiple Sclerosis Brain injury

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https://www.readbyqxmd.com/read/28344072/osteopontin-metallothionen-i-ii-interactions-in-experimental-autoimmunune-encephalomyelitis
#1
Hrvoje Jakovac, Tanja Grubić Kezele, Sandra Šućurović, Biserka Mulac-Jeričević, Biserka Radošević-Stašić
Osteopontin (OPN), an extracellular matrix (ECM) glyco-phosphoprotein, plays an important role in autoimmune-mediated demyelinating diseases, including multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). As an integrin and CD44 binding protein it participates in bidirectional communication between the ECM and target cells and affects transduction pathways that maintain neuronal and immune cells homeostasis. Its biological activity is also heavily influenced by microenvironment, which stimulates the cleavage of OPN and changes its functions...
March 23, 2017: Neuroscience
https://www.readbyqxmd.com/read/28332093/pathogenic-implications-of-distinct-patterns-of-iron-and-zinc-in-chronic-ms-lesions
#2
Bogdan F Popescu, Josa M Frischer, Samuel M Webb, Mylyne Tham, Reginald C Adiele, Christopher A Robinson, Patrick D Fitz-Gibbon, Stephen D Weigand, Imke Metz, Susan Nehzati, Graham N George, Ingrid J Pickering, Wolfgang Brück, Simon Hametner, Hans Lassmann, Joseph E Parisi, Guo Yong, Claudia F Lucchinetti
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) in which oligodendrocytes, the CNS cells that stain most robustly for iron and myelin are the targets of injury. Metals are essential for normal CNS functioning, and metal imbalances have been linked to demyelination and neurodegeneration. Using a multidisciplinary approach involving synchrotron techniques, iron histochemistry and immunohistochemistry, we compared the distribution and quantification of iron and zinc in MS lesions to the surrounding normal appearing and periplaque white matter, and assessed the involvement of these metals in MS lesion pathogenesis...
March 22, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28317272/roles-of-ng2-glia-in-ischemic-stroke
#3
REVIEW
Fei-Er Song, Jia-Lv Huang, Si-Han Lin, Shuo Wang, Guo-Fen Ma, Xiao-Ping Tong
Recent studies have shown that a widely distributed class of glial cells, termed NG2-glia, engages in rapid signaling with surrounding neurons through direct synaptic contacts in the developing and mature central nervous system (CNS). This unique glial cell group has a typical function of proliferating and differentiating into oligodendrocytes during early development of the brain, which is crucial to axon myelin formation. Therefore, NG2-glia are also called oligodendrocyte precursor cells (OPCs). In vitro and in vivo studies reveal that NG2-glia expressing receptors and ion channels demonstrate functional significance for rapid signaling with neuronal synapses and modulation of neuronal activities in both physiological and pathological conditions...
March 19, 2017: CNS Neuroscience & Therapeutics
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
#4
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/28302163/matrix-metalloproteinase-activity-stimulates-n-cadherin-shedding-and-the-soluble-n-cadherin-ectodomain-promotes-classical-microglial-activation
#5
Katherine Conant, Stefano Daniele, P Lorenzo Bozzelli, Tsion Abdi, Amanda Edwards, Arek Szklarczyk, India Olchefske, David Ottenheimer, Kathleen Maguire-Zeiss
BACKGROUND: Matrix metalloproteinases (MMPs) are a family of enzymes that are typically released from intracellular stores to act on specific extracellular substrates. MMP expression and activity can be increased in a neuronal activity-dependent manner, and further increased in response to tissue injury. MMP substrates include cell adhesion molecules (CAMs) that are abundantly expressed in the brain and well positioned for membrane proximal cleavage. Importantly, CAM integrity is important to synaptic structure and axon-myelin interactions, and shed ectodomains may themselves influence cellular function...
March 17, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28274814/the-role-of-aquaporin-4-in-synaptic-plasticity-memory-and-disease
#6
REVIEW
Jacqueline A Hubbard, Jenny I Szu, Devin K Binder
Since the discovery of aquaporins, it has become clear that the various mammalian aquaporins play critical physiological roles in water and ion balance in multiple tissues. Aquaporin-4 (AQP4), the principal aquaporin expressed in the central nervous system (CNS, brain and spinal cord), has been shown to mediate CNS water homeostasis. In this review, we summarize new and exciting studies indicating that AQP4 also plays critical and unanticipated roles in synaptic plasticity and memory formation. Next, we consider the role of AQP4 in Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), neuromyelitis optica (NMO), epilepsy, traumatic brain injury (TBI), and stroke...
March 6, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28273763/the-influence-of-posterior-visual-pathway-damage-on-visual-information-processing-speed-in-multiple-sclerosis
#7
Iñigo Gabilondo, Oiane Rilo, Natalia Ojeda, Javier Pena, Ainara Gómez-Gastiasoro, Mar Mendibe Bilbao, Alfredo Rodríguez-Antigüedad, Alberto Cabrera, Ibai Diez, Naroa Ibarretxe-Bilbao
BACKGROUND: The injury of visual pathway and abnormalities of visual processing speed (VPS) are frequent in MS, but their association remains unexplored. OBJECTIVE: To evaluate the impact of posterior visual pathway structural and functional integrity on VPS of MS patients. METHODS: Cross-sectional study of 30 MS patients and 28 controls, evaluating the association of a VPS tests composite (Salthouse Perceptual Comparison test, Trail Making Test A and Symbol Digit Modalities Test) with 3T MRI visual cortex thickness, optic radiations (OR) diffusion tensor imaging indexes, and medial visual component (MVC) functional connectivity (FC) (MVC-MVC FC (iFC) and MVC-brain FC (eFC)) by linear regression, removing the effect of premorbid IQ, fatigue, and depression...
November 1, 2016: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28272763/when-are-metabolic-ratios-superior-to-absolute-quantification-a-statistical-analysis
#8
Sarah E Hoch, Ivan I Kirov, Assaf Tal
Metabolite levels measured using magnetic resonance spectroscopy (MRS) are often expressed as ratios rather than absolute concentrations. However, the inter-subject variability of the denominator metabolite can introduce uncertainty into a metabolite ratio. In a clinical setting, there are no guidelines on whether ratios or absolute quantification should be used for a more accurate classification of normal versus abnormal results based on their statistical properties. In a research setting, the choice of one over the other can have significant implications on sample size, which must be factored in at the study design stage...
March 8, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28262404/breakthroughs-in-the-spasticity-management-are-non-pharmacological-treatments-the-future
#9
REVIEW
Antonino Naro, Antonino Leo, Margherita Russo, Carmela Casella, Antonio Buda, Aurelio Crespantini, Bruno Porcari, Luigi Carioti, Luana Billeri, Alessia Bramanti, Placido Bramanti, Rocco Salvatore Calabrò
The present paper aims at providing an objective narrative review of the existing non-pharmacological treatments for spasticity. Whereas pharmacologic and conventional physiotherapy approaches result well effective in managing spasticity due to stroke, multiple sclerosis, traumatic brain injury, cerebral palsy and incomplete spinal cord injury, the real usefulness of the non-pharmacological ones is still debated. We performed a narrative literature review of the contribution of non-pharmacological treatments to spasticity management, focusing on the role of non-invasive neurostimulation protocols (NINM)...
March 3, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28252608/-clinical-guidelines-for-the-use-of-dimethyl-fumarate-in-relapsing-remitting-multiple-sclerosis
#10
V M Alifirova, A N Boiko, Ya V Vlasov, M V Davydovskaya, M N Zakharova, N A Malkova, E V Popova, S A Sivertseva, N N Spirin, N V Khachanova, Т Е Shmidt
Multiple sclerosis is a chronic demyelinating and neurodegenerative disease of the central nervous system, in which autoimmune inflammation and oxidative stress play essential pathogenetic roles. Activation and infiltration of immune cells in brain tissues, lipid peroxidation products, mitochondrial dysfunction, defective antioxidant protection, and many other pathological factors result in demyelination, axonal injury and death, and apoptosis of oligodendrocytes and neurons, all of which causes constant progression of the disease...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28251686/e6020-a-synthetic-tlr4-agonist-accelerates-myelin-debris-clearance-schwann-cell-infiltration-and-remyelination-in-the-rat-spinal-cord
#11
Jamie S Church, Lindsay M Milich, Jessica K Lerch, Phillip G Popovich, Dana M McTigue
Oligodendrocyte progenitor cells (OPCs) are present throughout the adult brain and spinal cord and can replace oligodendrocytes lost to injury, aging, or disease. Their differentiation, however, is inhibited by myelin debris, making clearance of this debris an important step for cellular repair following demyelination. In models of peripheral nerve injury, TLR4 activation by lipopolysaccharide (LPS) promotes macrophage phagocytosis of debris. Here we tested whether the novel synthetic TLR4 agonist E6020, a Lipid A mimetic, promotes myelin debris clearance and remyelination in spinal cord white matter following lysolecithin-induced demyelination...
March 2, 2017: Glia
https://www.readbyqxmd.com/read/28218343/immediate-affective-responses-of-gait-training-in-neurological-rehabilitation-a-randomized-crossover-trial
#12
Martin Niedermeier, Larissa Ledochowski, Andreas Mayr, Leopold Saltuari, Martin Kopp
OBJECTIVE: To examine the immediate effects of physical therapy and robotic-assisted gait training on affective responses of gait training in neurological rehabilitation. DESIGN: Randomized crossover trial with blinded observers. PATIENTS: Sixteen patients with neurological disorders (stroke, traumatic brain injury, spinal cord injury, multiple sclerosis). METHODS: All patients underwent 2 single treatment sessions: physical therapy and robotic-assisted gait training...
February 16, 2017: Journal of Rehabilitation Medicine
https://www.readbyqxmd.com/read/28213892/opportunities-for-repurposing-of-poly-adp-ribose-polymerase-parp-inhibitors-for-the-therapy-of-non-oncological-diseases
#13
REVIEW
Nathan A Berger, Valerie C Besson, A Hamid Boulares, Alexander Bürkle, Alberto Chiarugi, Robert S Clark, Nicola J Curtin, Salvatore Cuzzocrea, Ted M Dawson, Valina L Dawson, György Haskó, Lucas Liaudet, Flavio Moroni, Pál Pacher, Peter Radermacher, Andrew L Salzman, Solomon H Snyder, Francisco Garcia Soriano, Robert P Strosznajder, Balázs Sümegi, Raymond A Swanson, Csaba Szabo
The recent clinical availability of the PARP inhibitor Lynparza (olaparib) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, indications where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, provide first-line options for therapeutic repurposing...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28198092/the-burden-of-neurological-disease-in-the-united-states-a-summary-report-and-call-to-action
#14
EDITORIAL
Clifton L Gooch, Etienne Pracht, Amy R Borenstein
The United States carries a substantial fiscal burden resulting from the nearly 100 million Americans with neurological disease. The combined annual costs of Alzheimer's and other dementias, low back pain, stroke, traumatic brain injury, migraine, epilepsy, multiple sclerosis, spinal cord injury and Parkinson's disease totals nearly 800 billion dollars and is rapidly rising due to the aging of the U.S. POPULATION: We provide a summary overview of the substantial current and future economic impact of neurological disease, and provide an action plan for reducing this burden through neurological research and enhanced clinical management of neurological disorders in the United States...
February 15, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28160128/blockade-of-the-kinin-b1-receptor-affects-the-cytokine-chemokine-profile-in-rat-brain-subjected-to-autoimmune-encephalomyelitis
#15
Karolina Podsiadło, Grzegorz Sulkowski, Beata Dąbrowska-Bouta, Lidia Strużyńska
Kinins are bioactive peptides which provide multiple functions, including critical regulation of the inflammatory response. Released during tissue injury, kinins potentiate the inflammation which represents a hallmark of numerous neurological disorders, including those of autoimmune origin such as multiple sclerosis (MS). In the present work, we assess the expression of B1 receptor (B1R) in rat brain during the course of experimental autoimmune encephalomyelitis (EAE) which is an animal model of MS. We apply pharmacological inhibition to investigate the role of this receptor in the development of neurological deficits and in shaping the cytokine/chemokine profile during the course of the disease...
February 3, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28148632/serum-neurofilament-is-associated-with-progression-of-brain-atrophy-and-disability-in-early-ms
#16
Jens Kuhle, Bardia Nourbakhsh, Donna Grant, Steve Morant, Christian Barro, Özgür Yaldizli, Daniel Pelletier, Gavin Giovannoni, Emmanuelle Waubant, Sharmilee Gnanapavan
OBJECTIVE: To investigate a potential effect of riluzole on serum neurofilaments (Nf) compared to placebo and the relationship between longitudinal clinical and MRI outcomes and serum Nf levels. METHODS: Serum samples were obtained from participants enrolled in a randomized double-blind trial of neuroprotection with riluzole vs placebo as an add-on to weekly interferon-β (IFN-β)-1a IM initiated 3 months after randomization. Nf measurements were performed by ELISA and electrochemiluminescence immunoassay...
February 28, 2017: Neurology
https://www.readbyqxmd.com/read/28139754/intranasal-delivery-of-a-novel-amnion-cell-secretome-prevents-neuronal-damage-and-preserves-function-in-a-mouse-multiple-sclerosis-model
#17
Reas S Khan, Kimberly Dine, Bailey Bauman, Michael Lorentsen, Lisa Lin, Helayna Brown, Leah R Hanson, Aleta L Svitak, Howard Wessel, Larry Brown, Kenneth S Shindler
The ability of a novel intranasally delivered amnion cell derived biologic to suppress inflammation, prevent neuronal damage and preserve neurologic function in the experimental autoimmune encephalomyelitis animal model of multiple sclerosis was assessed. Currently, there are no existing optic nerve treatment methods for disease or trauma that result in permanent vision loss. Demyelinating optic nerve inflammation, termed optic neuritis, induces permanent visual dysfunction due to retinal ganglion cell damage in multiple sclerosis and experimental autoimmune encephalomyelitis...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28130201/ucp2-up-regulation-within-the-course-of-autoimmune-encephalomyelitis-correlates-with-t-lymphocyte-activation
#18
Alina Smorodchenko, Stephanie Schneider, Anne Rupprecht, Karoline Hilse, Soleman Sasgary, Ute Zeitz, Reinhold G Erben, Elena E Pohl
Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disorder of the central nervous system (CNS) associated with severe neurological disability. Reactive oxygen species (ROS) and mitochondrial dysfunction play a pivotal role in the pathogenesis of this disease. Several members of the mitochondrial uncoupling protein subfamily (UCP2-UCP5) were suggested to regulate ROS by diminishing the mitochondrial membrane potential and constitute therefore a promising pharmacological target for MS. To evaluate the role of different uncoupling proteins in neuroinflammation, we have investigated their expression patterns in murine brain and spinal cord (SC) during different stages of experimental autoimmune encephalomyelitis (EAE), an animal model for MS...
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28114887/the-effect-of-omega-3-fatty-acids-on-central-nervous-system-remyelination-in-fat-1-mice
#19
Elise Siegert, Friedemann Paul, Michael Rothe, Karsten H Weylandt
BACKGROUND: There is a large body of experimental evidence suggesting that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are capable of modulating immune function. Some studies have shown that these PUFAs might have a beneficial effect in patients suffering form multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system (CNS). This could be due to increased n-3 PUFA-derived anti-inflammatory lipid mediators. In the present study we tested the effect of an endogenously increased n-3 PUFA status on cuprizone-induced CNS demyelination and remyelination in fat-1 mice versus their wild-type (wt) littermates...
January 24, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28107804/clinically-relevant-levels-of-4-aminopyridine-strengthen-physiological-responses-in-intact-motor-circuits-in-rats-especially-after-pyramidal-tract-injury
#20
Anil Sindhurakar, Asht M Mishra, Disha Gupta, Jennifer F Iaci, Tom J Parry, Jason B Carmel
BACKGROUND: 4-Aminopyridine (4-AP) is a Food and Drug Administration-approved drug to improve motor function in people with multiple sclerosis. Preliminary results suggest the drug may act on intact neural circuits and not just on demyelinated ones. OBJECTIVE: To determine if 4-AP at clinically relevant levels alters the excitability of intact motor circuits. METHODS: In anesthetized rats, electrodes were placed over motor cortex and the dorsal cervical spinal cord for electrical stimulation, and electromyogram electrodes were inserted into biceps muscle to measure responses...
April 2017: Neurorehabilitation and Neural Repair
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