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Multiple Sclerosis Brain injury

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https://www.readbyqxmd.com/read/28541408/loss-of-homeostatic-microglia-and-patterns-of-their-activation-in-active-multiple-sclerosis
#1
Tobias Zrzavy, Simon Hametner, Isabella Wimmer, Oleg Butovsky, Howard L Weiner, Hans Lassmann
Microglia and macrophages accumulate at the sites of active demyelination and neurodegeneration in the multiple sclerosis brain and are thought to play a central role in the disease process. We used recently described markers to characterize the origin and functional states of microglia/macrophages in acute, relapsing and progressive multiple sclerosis. We found microglia activation in normal white matter of controls and that the degree of activation increased with age. This microglia activation was more pronounced in the normal-appearing white matter of patients in comparison to controls and increased with disease duration...
May 24, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28540600/microglial-interferon-signaling-and-white-matter
#2
Ashley McDonough, Richard V Lee, Jonathan R Weinstein
Microglia, the resident immune cells of the CNS, are primary regulators of the neuroimmune response to injury. Type I interferons (IFNs), including the IFNαs and IFNβ, are key cytokines in the innate immune system. Their activity is implicated in the regulation of microglial function both during development and in response to neuroinflammation, ischemia, and neurodegeneration. Data from numerous studies in multiple sclerosis (MS) and stroke suggest that type I IFNs can modulate the microglial phenotype, influence the overall neuroimmune milieu, regulate phagocytosis, and affect blood-brain barrier integrity...
May 25, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28534174/the-il-1%C3%AE-phenomena-in-neuroinflammatory-diseases
#3
REVIEW
Andrew S Mendiola, Astrid E Cardona
It is becoming increasingly clear that neuroinflammation has a causal role in the pathogenesis of central nervous system (CNS)-related diseases, and therefore therapeutic strategies targeting the regulation or availability of inflammatory mediators can be used to prevent or mitigate pathology. Interestingly, the proinflammatory cytokine, interleukin-1 beta (IL-1β), has been implicated in perpetuating immune responses and contributing to disease severity in a variety of CNS diseases ranging from multiple sclerosis, neurodegenerative diseases, traumatic brain injury, and diabetic retinopathy...
May 22, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28505283/oxidative-injury-and-iron-redistribution-are-pathological-hallmarks-of-marmoset-experimental-autoimmune-encephalomyelitis
#4
Jordon Dunham, Jan Bauer, Graham R Campbell, Don J Mahad, Nikki van Driel, Susanne M A van der Pol, Bert A 't Hart, Hans Lassmann, Jon D Laman, Jack van Horssen, Yolanda S Kap
Oxidative damage and iron redistribution are associated with the pathogenesis and progression of multiple sclerosis (MS), but these aspects are not entirely replicated in rodent experimental autoimmune encephalomyelitis (EAE) models. Here, we report that oxidative burst and injury as well as redistribution of iron are hallmarks of the MS-like pathology in the EAE model in the common marmoset. Active lesions in the marmoset EAE brain display increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p22phox, p47phox, and gp91phox) and inducible nitric oxide synthase immunoreactivity within lesions with active inflammation and demyelination, coinciding with enhanced expression of mitochondrial heat-shock protein 70 and superoxide dismutase 1 and 2...
June 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28499503/mast-cells-in-neuroinflammation-and-brain-disorders
#5
REVIEW
Erik Hendriksen, Doris van Bergeijk, Ronald S Oosting, Frank A Redegeld
It is well recognized that neuroinflammation is involved in the pathogenesis of various neurodegenerative diseases. Microglia and astrocytes are major pathogenic components within this process and known to respond to proinflammatory mediators released from immune cells such as mast cells. Mast cells reside in the brain and are an important source of inflammatory molecules. Mast cell interactions with glial cells and neurons result in the release of mediators such as cytokines, proteases and reactive oxygen species...
May 10, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28497982/neuroprotection-in-oxidative-stress-related-neurodegenerative-diseases-role-of-endocannabinoid-system-modulation
#6
Janos Paloczi, Zoltan V Varga, George Hasko, Pal Pacher
SIGNIFICANCE: Redox imbalance may lead to overproduction of reactive oxygen and nitrogen species (ROS/RNS) and subsequent oxidative tissue damage which is a critical event in the course of neurodegenerative diseases. It is still not fully elucidated, however, whether oxidative stress is the primary trigger or a consequence in process of neurodegeneration. Recent Advances: Increasing evidence suggests that oxidative stress is involved in the propagation of neuronal injury and consequent inflammatory response, which in concert promote development of pathological alterations characteristic of most common neurodegenerative diseases...
May 12, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28488804/three-dimensional-shape-and-surface-features-distinguish-multiple-sclerosis-lesions-from-nonspecific-white-matter-disease
#7
Braeden D Newton, Katy Wright, Mandy D Winkler, Francesca Bovis, Masaya Takahashi, Ivan E Dimitrov, Maria Pia Sormani, Marco C Pinho, Darin T Okuda
BACKGROUND AND PURPOSE: There remains a need to further refine the ability of clinicians to differentiate multiple sclerosis (MS) from other disease etiologies. Here, we illustrate the value of 3-dimensional (3D) geometric shape and surface lesion characteristics between disease states. METHODS: Standardized 3-Tesla 3D brain magnetic resonance imaging studies were performed on enrolled MS and nonspecific white matter (NSWM) patients. Focal supratentorial lesions were identified, reconstructed using maximum intensity projection, manually segmented, and 3D printed...
May 10, 2017: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/28470695/sublethal-oligodendrocyte-injury-a-reversible-condition-in-multiple-sclerosis
#8
Qiao-Ling Cui, Damla Khan, Malena Rone, Vijayaraghava Rao, Radia Marie Johnson, Yun Hsuan Lin, Philippe-Antoine Bilodeau, Jeffery A Hall, Moses Rodriguez, Timothy E Kennedy, Samuel K Ludwin, Jack P Antel
OBJECTIVE: Degeneration of oligodendroglial distal processes has been identified as an early event in MS lesion development. Our objective was to further define the development of the "dying-back" oligodendrocyte lesion in situ and to model the development and potential reversibility of such responses using dissociated cultures of adult human brain-derived oligodendrocytes. Methods In situ analyses were performed on glutaraldehyde-fixed thin sections of clinically acute and pathologically active cases of MS...
May 3, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28444635/the-leukocentric-theory-of-neurological-disorder-a-manifesto
#9
Robert Fern
Approximately half of the human brain is composed of white matter (WM), a specialized tissue housing the axonal projection of neurons and their necessary supporting glial cells. Axons course long distances from their parent soma, have a delicate structure, large surface area and in many cases are dependent upon a uniquely close morphological arrangement with myelinating oligodendrocyte partners; all factors that may predispose them to injury and disease. WM damage is central to a range of well-characterized disorders including multiple sclerosis and spinal cord injury and is also makes a significant contribution to disorders often considered to be largely focused in gray matter; for example, in stroke where ~49% of injury by volume is located in WM...
April 25, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28440186/the-double-roles-of-the-prostaglandin-e2-ep2-receptor-in-intracerebral-hemorrhage
#10
Xu Luo, Qiquan Zhu, Jie Zhang, Qin Huang, Zongyi Xie, Yuan Cheng
Intracerebral hemorrhage (ICH), a subtype of stroke, brings high morbidity and mortality to human beings. Multiple studies indicate that neuroinflammation, excitotoxicity, oxidative stress, cytotoxicity resulted from the degradation products of blood clot play vital roles in ICH-induced secondary brain injury, which contributes to deterioration of neurological outcome. Prostaglandin E2 (PGE2), a type of prostanoids commonly up-regulated in these progresses, is known to modulate numerous cellular and molecular processes and involve in various diseases, including ICH, cerebral ischemic, Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) etc...
April 24, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28396703/characteristics-and-incidence-of-traumatic-brain-injury-in-older-adults-using-home-care-in-ontario-from-2003-2013
#11
Connor McGuire, Vicki L Kristman, Lynn Martin, Michel Bédard
OBJECTIVES: Describe the characteristics and determine the annual cumulative incidence of traumatic brain injury (TBI) in older adults receiving home care in Ontario from 2003 to 2013. METHODS: A retrospective cohort study of longitudinal data from the Ontario Association of Community Care Access Centers (N = 554,313). TBI, demographic variables, depression, neurological conditions, and recent falls were measured from the Resident Assessment Instrument-Home Care...
March 2017: Canadian Geriatrics Journal: CGJ
https://www.readbyqxmd.com/read/28385180/the-role-of-exosomes-in-cns-inflammation-and-their-involvement-in-multiple-sclerosis
#12
REVIEW
Igor Selmaj, Marcin P Mycko, Cedric S Raine, Krzysztof W Selmaj
Multiple sclerosis (MS) is a putative autoimmune disease of the central nervous system (CNS) in which autoreactive immune cells recognizing myelin antigens lead to demyelination and axonal injury. Mechanisms relevant to the pathogenesis of MS have not been fully elucidated, particularly those underlying initiation of immune system dysfunction. For example, it is not known how reactivity against CNS components is generated within the peripheral immune system. In this review, we propose that a significant contribution to the immunoregulatory events may derive from a cell-to-cell communication system involving the production, secretion and transfer of extracellular vesicles known as exosomes...
May 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28376127/the-doc-screen-feasible-and-valid-screening-for-depression-obstructive-sleep-apnea-osa-and-cognitive-impairment-in-stroke-prevention-clinics
#13
Richard H Swartz, Megan L Cayley, Krista L Lanctôt, Brian J Murray, Ashley Cohen, Kevin E Thorpe, Michelle N Sicard, Karen Lien, Demetrios J Sahlas, Nathan Herrmann
BACKGROUND: Post-stroke Depression, Obstructive sleep apnea (OSA) and Cognitive impairment ("DOC") are associated with greater mortality, worse recovery and poorer quality of life. Best practice recommendations endorse routine screening for each condition; yet, all are under-assessed, diagnosed and treated. We seek to determine the feasibility and validity of an integrated tool ("DOC" screen) to identify stroke clinic patients at high-risk of depression, OSA, and cognitive impairment...
2017: PloS One
https://www.readbyqxmd.com/read/28371088/cerebral-gray-matter-atrophy-is-associated-with-the-csf-igg-index-in-african-american-with-multiple-sclerosis
#14
Navid Seraji-Bozorgzad, Omar Khan, Bruce A C Cree, Fen Bao, Christina Caon, Imad Zak, Sara Razmjou, Alexandros Tselis, Scott Millis, Evanthia Bernitsas
BACKGROUND AND PURPOSE: African American (AA) patients with multiple sclerosis (MS) have been reported to have a more aggressive disease course compared to their white counterparts. We explored the relation of gray matter (GM) volume, a marker of tissue injury, and cerebrospinal fluid (CSF) IgG index in both AA and white MS patients. METHODS: This was a cross-sectional study of 150 self-identified AA and 150 white patients with MS who underwent magnetic resonance imaging scan of brain and CSF sampling...
March 29, 2017: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/28369944/increasing-acetyl-coa-metabolism-attenuates-injury-and-alters-spinal-cord-lipid-content-in-mice-subjected-to-experimental-autoimmune-encephalomyelitis
#15
Amber C Chevalier, Thad A Rosenberger
Acetate supplementation increases brain acetyl-CoA metabolism, alters histone and non-histone protein acetylation, increases brain energy reserves, and is anti-inflammatory and neuroprotective in rat models of neuroinflammation and neuroborreliosis. To determine the impact acetate supplementation has on a mouse model of multiple sclerosis, we quantified the effect treatment had on injury progression, spinal cord lipid content, phospholipase levels, and myelin structure in mice subjected to experimental autoimmune encephalomyelitis (EAE)...
March 31, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28344072/osteopontin-metallothionein-i-ii-interactions-in-experimental-autoimmunune-encephalomyelitis
#16
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 cell homeostasis. Its biological activity is also heavily influenced by microenvironment, which stimulates the cleavage of OPN and changes its functions...
March 24, 2017: Neuroscience
https://www.readbyqxmd.com/read/28332093/pathogenic-implications-of-distinct-patterns-of-iron-and-zinc-in-chronic-ms-lesions
#17
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
#18
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
#19
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
#20
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
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