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https://www.readbyqxmd.com/read/28093709/molecular-genetic-and-epigenetic-basis-of-multiple-sclerosis
#1
Zohreh Hojati
Multiple Sclerosis (MS) is a chronic immune-mediated disease of spinal cord and brain. The initial event in MS occurs when activated CD4(+) T cells in periphery exacerbates immune responses by stimulating immune cells such as B cells, CD8(+) cells, mast cells, granulocytes and monocytes. These proinflammatory cells pass blood brain barrier by secreting proinflammatory cytokines including TNF-α and INF-γ which activate adhesion factors. APCs (antigen-presenting cells) reactivate CD4(+) T cells after infiltrating the CNS and CD4(+) T cells produce cytokines and chemokines...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28087836/neuropathological-consequences-of-gestational-exposure-to-concentrated-ambient-fine-and-ultrafine-particles-in-the-mouse
#2
Carolyn Klocke, Joshua L Allen, Marissa Sobolewski, Margot Mayer-Pröschel, Jason L Blum, Dana Lauterstein, Judith T Zelikoff, Deborah A Cory-Slechta
Increasing evidence indicates that the central nervous system (CNS) is a target of air pollution. We previously reported that postnatal exposure of mice to concentrated ambient ultrafine particles (UFP; ≤100nm) via the University of Rochester HUCAPS system during a critical developmental window of CNS development, equivalent to human 3(rd) trimester, produced male-predominant neuropathological and behavioral characteristics common to multiple neurodevelopmental disorders, including autism spectrum disorder (ASD), in humans...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28072884/structural-and-ultrastructural-alterations-in-human-olfactory-pathways-and-possible-associations-with-herpesvirus-6-infection
#3
Sandra Skuja, Anete Zieda, Kristine Ravina, Svetlana Chapenko, Silvija Roga, Ojars Teteris, Valerija Groma, Modra Murovska
Structural and ultrastructural alterations in human olfactory pathways and putative associations with human herpesvirus 6 (HHV-6) infection were studied. The olfactory bulb/tract samples from 20 subjects with an unspecified encephalopathy determined by pathomorphological examination of the brain autopsy, 17 healthy age-matched and 16 younger controls were used. HHV-6 DNA was detected in 60, 29, and 19% of cases in these groups, respectively. In the whole encephalopathy group, significantly more HHV-6 positive neurons and oligodendrocytes were found in the gray matter, whereas, significantly more HHV-6 positive astrocytes, oligodendrocytes, microglia/macrophages and endothelial cells were found in the white matter...
2017: PloS One
https://www.readbyqxmd.com/read/28069926/creatine-enhances-mitochondrial-mediated-oligodendrocyte-survival-following-demyelinating-injury
#4
Kelly A Chamberlain, Kristen S Chapey, Sonia E Nanescu, Jeffrey K Huang
: Chronic oligodendrocyte loss, which occurs in the demyelinating disorder multiple sclerosis (MS), contributes to axonal dysfunction and neurodegeneration. Current therapies are able to reduce MS severity, but do not prevent transition into the progressive phase of the disease, which is characterized by chronic neurodegeneration. Therefore, pharmacological compounds that promote oligodendrocyte survival could be beneficial for neuroprotection in MS. Here, we investigated the role of creatine, an organic acid involved in ATP buffering, in oligodendrocyte function...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27988845/an-updated-histological-classification-system-for-multiple-sclerosis-lesions
#5
Tanja Kuhlmann, Samuel Ludwin, Alexandre Prat, Jack Antel, Wolfgang Brück, Hans Lassmann
Multiple sclerosis is a complex and heterogeneous, most likely autoimmune, demyelinating disease of the central nervous system (CNS). Although a number of histological classification systems for CNS lesions have been used by different groups in recent years, no uniform classification exists. In this paper, we propose a simple and unifying classification of MS lesions incorporating many elements of earlier histological systems that aims to provide guidelines for neuropathologists and researchers studying MS lesions to allow for better comparison of different studies performed with MS tissue, and to aid in understanding the pathogenesis of the disease...
January 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/27938480/human-amnion-epithelial-cells-protect-against-white-matter-brain-injury-after-repeated-endotoxin-exposure-in-the-preterm-ovine-fetus
#6
Tamara Yawno, Tharani Sabaretnam, Jingang Li, Courtney McDonald, Rebecca Lim, Graham Jenkin, Euan Wallace, Suzanne Miller
<p>Intrauterine inflammation is a significant cause of injury to the developing fetal brain. Using a preterm fetal sheep model of in utero infection, we asked whether human amnion epithelial cells (hAECs) were able to reduce inflammation-induced fetal brain injury.</p><p>Surgery was undertaken on pregnant sheep at ~105 days gestation (term is 147 days) for implantation of vascular catheters. Lipopolysaccharide (LPS; 150 ng/kg bolus) or saline was administered iv at 109, 110 and 111 days. 60 million fluorescent-labeled hAECs were administered at 110, 111, and 112 days gestation via the brachial artery catheter...
31, 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27904823/expression-of-gp91phox-and-p22phox-catalytic-subunits-of-nadph-oxidase-on-microglia-in-nasu-hakola-disease-brains
#7
Jun-Ichi Satoh, Yoshihiro Kino, Motoaki Yanaizu, Youhei Tosaki, Kenji Sakai, Tusyoshi Ishida, Yuko Saito
The superoxide-producing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex of phagocytes (phox) plays a key role in production of reactive oxygen species (ROS) by microglia. The catalytic subunits of the NADPH oxidase are composed of p22phox and gp91phox. Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder caused by a loss-of-function mutation of either TYROBP (DAP12) or TREM2. Pathologically, the brains of NHD patients exhibit extensive demyelination designated leukoencephalopathy, astrogliosis, accumulation of axonal spheroids, and remarkable activation of microglia predominantly in the white matter of frontal and temporal lobes...
November 2016: Intractable & Rare Diseases Research
https://www.readbyqxmd.com/read/27903432/antigen-presentation-for-priming-t-cells-in-central-system
#8
Shaoni Dasgupta, Subhajit Dasgupta
Generation of myelin antigen-specific T cells is a major event in neuroimmune responses that causes demyelination. The antigen-priming of T cells and its location is important in chronic and acute inflammation. In autoimmune multiple sclerosis, the effector T cells are considered to generate in periphery. However, the reasons for chronic relapsing-remitting events are obscure. Considering mechanisms, a feasible aim of research is to investigate the role of antigen-primed T cells in lupus cerebritis. Last thirty years of investigations emphasize the relevance of microglia and infiltrated dendritic cells/macrophages as antigen presenting cells in the central nervous system...
January 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27888476/histological-detection-of-dynamic-glial-responses-in-the-dysmyelinating-tabby-jimpy-mutant-brain
#9
Masanao Ikeda, M Ibrahim Hossain, Li Zhou, Masao Horie, Kazuhiro Ikenaka, Arata Horii, Hirohide Takebayashi
Oligodendrocytes (OLs) are glial cells that form myelin sheaths surrounding the axons in the central nervous system (CNS). Jimpy (jp) mutant mice are dysmyelinating disease models that show developmental abnormalities in myelinated OLs in the CNS. The causative gene in jp mice is the proteolipid protein (PLP) located on the X chromosome. Mutations in the jp allele result in exon 5 skipping and expression of abnormal PLP containing a C-terminal frame shift. Many lines of evidence suggest that abnormal PLP in OLs results in endoplasmic reticulum (ER) stress and cell death...
November 25, 2016: Anatomical Science International
https://www.readbyqxmd.com/read/27859676/microglia-and-brain-macrophages-an-update
#10
REVIEW
Atsushi Sasaki
Current immunohistochemical techniques have made the identification of microglia possible in routinely processed tissue sections from human brains. Previous studies have indicated that almost no neurological diseases exist without microglial activation. Activated microglia often secrete inflammatory cytokines in various diseases, including Alzheimer's disease, but microglial activation is not always associated with inflammation. The equation microglial activation means "neuroinflammation" is absurd and misleading...
November 18, 2016: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/27853421/transient-developmental-purkinje-cell-axonal-torpedoes-in-healthy-and-ataxic-mouse-cerebellum
#11
Lovisa Ljungberg, Daneck Lang-Ouellette, Angela Yang, Sriram Jayabal, Sabrina Quilez, Alanna J Watt
Information is carried out of the cerebellar cortical microcircuit via action potentials propagated along Purkinje cell axons. In several human neurodegenerative diseases, focal axonal swellings on Purkinje cells - known as torpedoes - have been associated with Purkinje cell loss. Interestingly, torpedoes are also reported to appear transiently during development in rat cerebellum. The function of Purkinje cell axonal torpedoes in health as well as in disease is poorly understood. We investigated the properties of developmental torpedoes in the postnatal mouse cerebellum of wild-type and transgenic mice...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27844029/dose-dependent-inhibition-of-demyelination-and-microglia-activation-by-ivig
#12
Meike Winter, Christine Baksmeier, Julia Steckel, Sumanta Barman, Manish Malviya, Melanie Harrer-Kuster, Hans-Peter Hartung, Norbert Goebels
OBJECTIVE: Intravenous immunoglobulin (IVIG) is an established treatment for numerous autoimmune conditions. Clinical trials of IVIG for multiple sclerosis, using diverse dose regimens, yielded controversial results. The aim of this study is to dissect IVIG effector mechanisms on demyelination in an ex vivo model of the central nervous system (CNS)-immune interface. METHODS: Using organotypic cerebellar slice cultures (OSC) from transgenic mice expressing green fluorescent protein (GFP) in oligodendrocytes/myelin, we induced extensive immune-mediated demyelination and oligodendrocyte loss with an antibody specific for myelin oligodendrocyte glycoprotein (MOG) and complement...
November 2016: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/27818624/glial-cell-contributions-to-auditory-brainstem-development
#13
REVIEW
Karina S Cramer, Edwin W Rubel
Glial cells, previously thought to have generally supporting roles in the central nervous system, are emerging as essential contributors to multiple aspects of neuronal circuit function and development. This review focuses on the contributions of glial cells to the development of auditory pathways in the brainstem. These pathways display specialized synapses and an unusually high degree of precision in circuitry that enables sound source localization. The development of these pathways thus requires highly coordinated molecular and cellular mechanisms...
2016: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/27814521/the-central-nervous-system-and-the-gut-microbiome
#14
REVIEW
Gil Sharon, Timothy R Sampson, Daniel H Geschwind, Sarkis K Mazmanian
Neurodevelopment is a complex process governed by both intrinsic and extrinsic signals. While historically studied by researching the brain, inputs from the periphery impact many neurological conditions. Indeed, emerging data suggest communication between the gut and the brain in anxiety, depression, cognition, and autism spectrum disorder (ASD). The development of a healthy, functional brain depends on key pre- and post-natal events that integrate environmental cues, such as molecular signals from the gut...
November 3, 2016: Cell
https://www.readbyqxmd.com/read/27796537/slow-expansion-of-multiple-sclerosis-iron-rim-lesions-pathology-and-7%C3%A2-t-magnetic-resonance-imaging
#15
Assunta Dal-Bianco, Günther Grabner, Claudia Kronnerwetter, Michael Weber, Romana Höftberger, Thomas Berger, Eduard Auff, Fritz Leutmezer, Siegfried Trattnig, Hans Lassmann, Francesca Bagnato, Simon Hametner
In multiple sclerosis (MS), iron accumulates inside activated microglia/macrophages at edges of some chronic demyelinated lesions, forming rims. In susceptibility-based magnetic resonance imaging at 7 T, iron-laden microglia/macrophages induce a rim of decreased signal at lesion edges and have been associated with slowly expanding lesions. We aimed to determine (1) what lesion types and stages are associated with iron accumulation at their edges, (2) what cells at the lesion edges accumulate iron and what is their activation status, (3) how reliably can iron accumulation at the lesion edge be detected by 7 T magnetic resonance imaging (MRI), and (4) if lesions with rims enlarge over time in vivo, when compared to lesions without rims...
January 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/27761896/transitory-cystic-cavities-in-the-developing-mammalian-brain-normal-or-anomalous
#16
Charanjit Kaur, Eng-Ang Ling
Transitory cavities associated with the ventricular system represent probably one of the most unique features in the developing mammalian brain. In rodents, the cavities exist transiently in the developing brain and do not appear to be associated with any pathological events. Among the various cavities, the pyramidal-shaped cavum septum pellucidum (CSP) located beneath the corpus callosum and between the lateral ventricles is most well defined. In addition to the CSP are the bilateral subependymal cysts that are consistently associated with the third and fourth ventricles as well as the aqueduct...
October 20, 2016: Journal of Anatomy
https://www.readbyqxmd.com/read/27761801/phrenic-nerve-deficits-and-neurological-immunopathology-associated-with-acute-west-nile-virus-infection-in-mice-and-hamsters
#17
Katherine Zukor, Hong Wang, Brett L Hurst, Venkatraman Siddharthan, Arnaud Van Wettere, Paul M Pilowsky, John D Morrey
Neurological respiratory deficits are serious outcomes of West Nile virus (WNV) disease. WNV patients requiring intubation have a poor prognosis. We previously reported that WNV-infected rodents also appear to have respiratory deficits when assessed by whole-body plethysmography and diaphragmatic electromyography. The purpose of this study was to determine if the nature of the respiratory deficits in WNV-infected rodents is neurological and if deficits are due to a disorder of brainstem respiratory centers, cervical spinal cord (CSC) phrenic motor neuron (PMN) circuitry, or both...
October 19, 2016: Journal of Neurovirology
https://www.readbyqxmd.com/read/27713744/peripheral-and-central-neuroinflammatory-changes-and-pain-behaviors-in-an-animal-model-of-multiple-sclerosis
#18
Samuel S Duffy, Chamini J Perera, Preet G S Makker, Justin G Lees, Pascal Carrive, Gila Moalem-Taylor
Pain is a widespread and debilitating symptom of multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system. Although central neuroinflammation and demyelination have been implicated in MS-related pain, the contribution of peripheral and central mechanisms during different phases of the disease remains unclear. In this study, we used the animal model experimental autoimmune encephalomyelitis (EAE) to examine both stimulus-evoked and spontaneous pain behaviors, and neuroinflammatory changes, over the course of chronic disease...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27699230/a-cord-blood-monocyte-derived-cell-therapy-product-accelerates-brain-remyelination
#19
Arjun Saha, Susan Buntz, Paula Scotland, Li Xu, Pamela Noeldner, Sachit Patel, Amy Wollish, Aruni Gunaratne, Tracy Gentry, Jesse Troy, Glenn K Matsushima, Joanne Kurtzberg, Andrew E Balber
Microglia and monocytes play important roles in regulating brain remyelination. We developed DUOC-01, a cell therapy product intended for treatment of demyelinating diseases, from banked human umbilical cord blood (CB) mononuclear cells. Immunodepletion and selection studies demonstrated that DUOC-01 cells are derived from CB CD14(+) monocytes. We compared the ability of freshly isolated CB CD14(+) monocytes and DUOC-01 cells to accelerate remyelination of the brains of NOD/SCID/IL2Rγ(null) mice following cuprizone feeding-mediated demyelination...
August 18, 2016: JCI Insight
https://www.readbyqxmd.com/read/27687291/transcriptomic-regulations-in-oligodendroglial-and-microglial-cells-related-to-brain-damage-following-fetal-growth-restriction
#20
Aline Rideau Batista Novais, Hoa Pham, Yohan Van de Looij, Miguel Bernal, Jerome Mairesse, Elodie Zana-Taieb, Marina Colella, Pierre-Henri Jarreau, Julien Pansiot, Florent Dumont, Stéphane Sizonenko, Pierre Gressens, Christiane Charriaut-Marlangue, Mickael Tanter, Charlie Demene, Daniel Vaiman, Olivier Baud
Fetal growth restriction (FGR) is a major complication of human pregnancy, frequently resulting from placental vascular diseases and prenatal malnutrition, and is associated with adverse neurocognitive outcomes throughout life. However, the mechanisms linking poor fetal growth and neurocognitive impairment are unclear. Here, we aimed to correlate changes in gene expression induced by FGR in rats and abnormal cerebral white matter maturation, brain microstructure, and cortical connectivity in vivo. We investigated a model of FGR induced by low-protein-diet malnutrition between embryonic day 0 and birth using an interdisciplinary approach combining advanced brain imaging, in vivo connectivity, microarray analysis of sorted oligodendroglial and microglial cells and histology...
December 2016: Glia
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