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Myelination microglia

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https://www.readbyqxmd.com/read/28638987/leukodystrophies-a-proposed-classification-system-based-on-pathological-changes-and-pathogenetic-mechanisms
#1
REVIEW
Marjo S van der Knaap, Marianna Bugiani
Leukodystrophies are genetically determined disorders characterized by the selective involvement of the central nervous system white matter. Onset may be at any age, from prenatal life to senescence. Many leukodystrophies are degenerative in nature, but some only impair white matter function. The clinical course is mostly progressive, but may also be static or even improving with time. Progressive leukodystrophies are often fatal, and no curative treatment is known. The last decade has witnessed a tremendous increase in the number of defined leukodystrophies also owing to a diagnostic approach combining magnetic resonance imaging pattern recognition and next generation sequencing...
June 21, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28629387/an-updated-assessment-of-microglia-depletion-current-concepts-and-future-directions
#2
REVIEW
Jinming Han, Robert A Harris, Xing-Mei Zhang
Microglia are the principal resident immune cells in the central nervous system and are believed to be versatile players in both inflammatory and physiological contexts. On the one hand, in order to safeguard the microenvironment microglia can be rapidly activated by contact with microbial products or cell debris, thereby exerting the functions of innate immunity via phagocytosis and secretion of cytokines and chemokines. Conversely, microglia can also assist in brain development, synaptic plasticity and neural repair through the production of neurotrophic factors and clearance of myelin debris...
June 19, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28625767/early-life-stress-perturbs-the-function-of-microglia-in-the-developing-rodent-brain-new-insights-and-future-challenges
#3
REVIEW
Frances K Johnson, Arie Kaffman
The role of the innate immune system in mediating some of the consequences of childhood abuse and neglect has received increasing attention in recent years. Most of the work to date has focused on the role that neuroinflammation plays in the long-term adult psychiatric and medical complications associated with childhood maltreatment. The effects of stress-induced neuroinflammation on neurodevelopment have received little attention because until recently this issue has not been studied systematically in animal models of early life stress...
June 15, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28618115/iron-sulfur-glutaredoxin-2-protects-oligodendrocytes-against-damage-induced-by-nitric-oxide-release-from-activated-microglia
#4
Klaudia Lepka, Katrin Volbracht, Eckhard Bill, Reiner Schneider, Natalia Rios, Thomas Hildebrandt, Jens Ingwersen, Timur Prozorovski, Christopher Horst Lillig, Jack van Horssen, Lawrence Steinman, Hans-Peter Hartung, Rafael Radi, Arne Holmgren, Orhan Aktas, Carsten Berndt
Demyelinated brain lesions, a hallmark of autoimmune neuroinflammatory diseases like multiple sclerosis, result from oligodendroglial cell damage. Activated microglia are considered a major source of nitric oxide and subsequent peroxynitrite-mediated damage of myelin. Here, we provide biochemical and biophysical evidence that the oxidoreductase glutaredoxin 2 inhibits peroxynitrite formation by transforming nitric oxide into dinitrosyl-diglutathionyl-iron-complexes. Glutaredoxin 2 levels influence both survival rates of primary oligodendrocyte progenitor cells and preservation of myelin structure in cerebellar organotypic slice cultures challenged with activated microglia or nitric oxide donors...
June 15, 2017: Glia
https://www.readbyqxmd.com/read/28606007/dimethyl-fumarate-improves-white-matter-function-following-severe-hypoperfusion-involvement-of-microglia-macrophages-and-inflammatory-mediators
#5
Jill H Fowler, Jamie McQueen, Philip R Holland, Yasmina Manso, Martina Marangoni, Fiona Scott, Emma Chisholm, Robert H Scannevin, Giles E Hardingham, Karen Horsburgh
The brain's white matter is highly vulnerable to reductions in cerebral blood flow via mechanisms that may involve elevated microgliosis and pro-inflammatory pathways. In the present study, the effects of severe cerebral hypoperfusion were investigated on white matter function and inflammation. Male C57Bl/6J mice underwent bilateral common carotid artery stenosis and white matter function was assessed at seven days with electrophysiology in response to evoked compound action potentials (CAPs) in the corpus callosum...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28593439/clinical-and-histopathological-amelioration-of-experimental-autoimmune-encephalomyelitis-by-aav-vectors-expressing-a-soluble-interleukin-23-receptor
#6
Marta Miralles, Herena Eixarch, Marcos Tejero, Carme Costa, Keiji Hirota, A Raul Castaño, Meritxell Puig, Gitta Stockinger, Xavier Montalban, Assumpció Bosch, Carmen Espejo, Miguel Chillon
The role of the T helper (Th)17 pathway has been clearly demonstrated in the onset and progression of autoimmune diseases, where interleukin (IL)-23 is a key molecule in maintaining the response mediated by Th17 cells. As a consequence, recent strategies based on blocking the interaction between IL-23 and its receptor (IL-23R), for example the anti-p19 antibody tildrakizumab, have been developed to regulate the Th17 pathway from the initial stages of the disease. Here, a soluble (s)IL-23R cDNA was cloned in expression plasmids and viral vectors...
June 7, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28586011/microglia-activation-triggers-oligodendrocyte-precursor-cells-apoptosis-via-hsp60
#7
Yunhong Li, Rui Zhang, Xiaolin Hou, Yumei Zhang, Feijia Ding, Fan Li, Yao Yao, Yin Wang
Reactive microglia are present in lesions of myelin‑associated white matter disorders resulting in injuries to oligodendrocyte precursor cells (OPCs). Therefore, protection of OPCs from injury due to excessive activation of microglia is important in treating these diseases. Heat shock protein 60 (HSP60) has been demonstrated to be released extracellularly in the failing heart upon stress or injury. However, the role of HSP60 in the central nervous system and whether it participates in the toxic effects of microglia on OPCs remains unclear...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28578430/expression-profiles-of-cholesterol-metabolism-related-genes-are-altered-during-development-of-experimental-autoimmune-encephalomyelitis-in-the-rat-spinal-cord
#8
Irena Lavrnja, Kosara Smiljanic, Danijela Savic, Aleksandra Mladenovic-Djordjevic, Katarina Tesovic, Selma Kanazir, Sanja Pekovic
Increased evidence suggests that dysregulation of cholesterol metabolism may be a key event contributing to progression of multiple sclerosis (MS). Using an experimental autoimmune encephalomyelitis (EAE) model of MS we revealed specific changes in the mRNA and protein expression of key molecules involved in the maintaining of cholesterol homeostasis in the rat spinal cord: 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR), apolipoprotein E (ApoE) and cholesterol 24-hydroxylase (CYP46A1) during the course of disease...
June 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28567989/the-novel-synthetic-microneurotrophin-bnn27-protects-mature-oligodendrocytes-against-cuprizone-induced-death-through-the-ngf-receptor-trka
#9
Giulia Bonetto, Ioannis Charalampopoulos, Achille Gravanis, Domna Karagogeos
BNN27, a member of a chemical library of C17-spiroepoxy derivatives of the neurosteroid DHEA, has been shown to regulate neuronal survival through its selective interaction with NGF receptors (TrkA and p75(NTR) ), but its role on glial populations has not been studied. Here, we present evidence that BNN27 provides trophic action (rescue from apoptosis), in a TrkA-dependent manner, to mature oligodendrocytes when they are challenged with the cuprizone toxin in culture. BNN27 treatment also increases oligodendrocyte maturation and diminishes microglia activation in vitro...
August 2017: Glia
https://www.readbyqxmd.com/read/28561815/effects-of-therapeutic-hypothermia-on-white-matter-injury-from-murine-neonatal-hypoxia-ischemia
#10
Elliot Koo, R Ann Sheldon, Byong Sop Lee, Zinaida S Vexler, Donna M Ferriero
BackgroundTherapeutic hypothermia (TH) is the standard of care for neonates with hypoxic-ischemic encephalopathy, but it is not fully protective in the clinical setting. Hypoxia-ischemia (HI) may cause white matter injury (WMI), leading to neurological and cognitive dysfunction.MethodsP9 mice were subjected to HI as previously described. Pups underwent 3.5 h of systemic hypothermia or normothermia. Cresyl violet and Perl's iron staining for histopathological scoring of brain sections was completed blindly on all brains...
May 31, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28535416/the-role-of-timing-in-the-treatment-of-spinal-cord-injury
#11
REVIEW
Amene Saghazadeh, Nima Rezaei
Regeneration failure after primary spinal cord injury (SCI) leads to diverse clinical complications in a severity- and level of SCI-dependent manner. The cost of treating both of them (initial regeneration failure and following complications) would be prohibitive, particularly in less developed nations. The well-recognized circumstances arose from primary SCI include excitotoxicity and inflammation. SCI increases concentrations of extracellular amino acids (EAAs) in the severity-dependent manner and the maximum level of EAAs at the injury site will be reduced by distance from the injury site...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28529876/pathology-of-callosal-damage-in-als-an-ex-vivo-7%C3%A2-t-diffusion-tensor-mri-study
#12
Agustin M Cardenas, Joelle E Sarlls, Justin Y Kwan, Devin Bageac, Zachary S Gala, Laura E Danielian, Abhik Ray-Chaudhury, Hao-Wei Wang, Karla L Miller, Sean Foxley, Saad Jbabdi, Robert C Welsh, Mary Kay Floeter
OBJECTIVES: The goal of this study was to better understand the changes in tissue microstructure that underlie white matter diffusion changes in ALS patients. METHODS: Diffusion tensor imaging was carried out in postmortem brains of 4 ALS patients and two subjects without neurological disease on a 7 T MRI scanner using steady-state free precession sequences. Fractional anisotropy (FA) was measured in the genu, body, and splenium of the corpus callosum in formalin-fixed hemispheres...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28504050/how-long-is-sufficient-for-optimal-neuroprotection-with-cerebral-cooling-after-ischemia-in-fetal-sheep
#13
Joanne O Davidson, Vittoria Draghi, Sean Whitham, Simerdeep K Dhillon, Guido Wassink, Laura Bennet, Alistair J Gunn
The optimal duration of mild "therapeutic" hypothermia for neonates with hypoxic-ischemic encephalopathy is surprisingly unclear. This study assessed the relative efficacy of cooling for 48 h versus 72 h. Fetal sheep (0.85 gestation) received sham ischemia (n = 9) or 30 min global cerebral ischemia followed by normothermia (n = 8) or delayed hypothermia from 3 h to 48 h (n = 8) or 72 h (n = 8). Ischemia was associated with profound loss of electroencephalogram (EEG) power, neurons in the cortex and hippocampus, and oligodendrocytes and myelin basic protein expression in the white matter, with increased Iba-1-positive microglia and proliferation...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28503634/an-acute-mouse-spinal-cord-slice-preparation-for-studying-glial-activation-ex-vivo
#14
Juan Mauricio Garré, Guang Yang, Feliksas F Bukauskas, Michael V L Bennett
Pathological conditions such as amyotrophic lateral sclerosis, spinal cord injury and chronic pain are characterized by activation of astrocytes and microglia in spinal cord and have been modeled in rodents. In vivo imaging at cellular level in these animal models is limited due to the spinal cord's highly myelinated funiculi. The preparation of acute slices may offer an alternative and valuable strategy to collect structural and functional information in vitro from dorsal, lateral and ventral regions of spinal cord...
January 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28498493/involvement-of-microglia-in-early-axoglial-alterations-of-the-optic-nerve-induced-by-experimental-glaucoma
#15
Melina P Bordone, María F González Fleitas, Laura A Pasquini, Alejandra Bosco, Pablo H Sande, Ruth E Rosenstein, Damián Dorfman
Glaucoma is a leading cause of blindness, characterized by retinal ganglion cell (RGC) loss and optic nerve (ON) damage. Cumulative evidence suggests glial cell involvement in the degeneration of the ON and RGCs. We analyzed the contribution of microglial reactivity to early axoglial alterations of the ON in an induced model of ocular hypertension. For this purpose, vehicle or chondroitin sulfate (CS) were weekly injected into the eye anterior chamber from Wistar rats for different intervals. The amount of Brn3a(+) RGC significantly decreased in CS-injected eyes for 10 and 15 (but not 6) weeks...
May 12, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28478826/novel-aspects-of-defensins-involvement-in-virus-induced-autoimmunity-in-the-central-nervous-system
#16
Evangelos I Kazakos, Jannis Kountouras, Stergios A Polyzos, Georgia Deretzi
Recent research on re-circulation of interstitial fluid from the brain parenchyma to the periphery and its inferred importance in immune surveillance dysregulation are changing our conceptualization of the pathophysiology of virus-induced autoimmunity. In this context, it is necessary to reassess the immunomodulatory properties of human defensins that are variably expressed by cerebral microglia, astrocytes and choroid plexus epithelial cells and exhibit complex and often confounding roles in neuroinflammatory processes...
May 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28466255/formyl-peptide-receptor-1-mediated-glial-cell-activation-in-a-mouse-model-of-cuprizone-induced-demyelination
#17
Kai Bihler, Eugenia Kress, Stefan Esser, Stella Nyamoya, Simone C Tauber, Tim Clarner, Matthias B Stope, Thomas Pufe, Lars-Ove Brandenburg
Multiple sclerosis (MS) is a chronic degenerative disease of the central nervous system that is characterized by myelin abnormalities, oligodendrocyte pathology, and concomitant glia activation. Unclear are the factors triggering gliosis and demyelination. New findings suggest an important role of the innate immune response in the initiation and progression of active demyelinating lesions. The innate immune response is induced by pathogen-associated or danger-associated molecular patterns, which are identified by pattern recognition receptors (PRRs), including the G-protein coupled with formyl peptide receptors (FPRs)...
June 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28457906/widespread-cortical-demyelination-of-both-hemispheres-can-be-induced-by-injection-of-pro-inflammatory-cytokines-via-an-implanted-catheter-in-the-cortex-of-mog-immunized-rats
#18
Muammer Üçal, Michaela Tanja Haindl, Milena Z Adzemovic, Johannes Strasser, Lisa Theisl, Manuel Zeitelhofer, Klaus Kraitsy, Stefan Ropele, Ute Schäfer, Franz Fazekas, Sonja Hochmeister
Cortical demyelination is a common finding in patients with chronic multiple sclerosis (MS) and contributes to disease progression and overall disability. The exact pathomechanism that leads to cortical lesions is not clear. Research is limited by the fact that standard animal models of multiple sclerosis do not commonly affect the cortex, or if they do in some variants, the cortical demyelination is rather sparse and already remyelinated within a few days. In an attempt to overcome these limitations we implanted a tissue-compatible catheter into the cortex of Dark Agouti rats...
August 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28452087/cytotoxic-cd8-t-cells-ablation-enhances-the-capacity-of-regulatory-t-cells-to-delay-viral-elimination-in-theiler-s-murine-encephalomyelitis
#19
Malgorzata Ciurkiewicz, Vanessa Herder, Muhammad Akram Khan, Ann-Kathrin Uhde, René Teich, Stephan Floess, Wolfgang Baumgärtner, Jochen Huehn, Andreas Beineke
Theiler's murine encephalomyelitis (TME) of susceptible mouse strains is a commonly used infectious animal model for multiple sclerosis. The study aim was to test the hypothesis whether cytotoxic T cell responses account for the limited impact of regulatory T cells on antiviral immunity in TME virus-induced demyelinating disease (TMEV-IDD) resistant C57BL/6 mice. TME virus-infected C57BL/6 mice were treated with (i) interleukin-2/-anti-interleukin-2-antibody-complexes to expand regulatory T cells ('Treg-expansion'), (ii) anti-CD8-antibodies to deplete cytotoxic T cells ('CD8-depletion') or (iii) with a combination of Treg-expansion and CD8-depletion ('combined treatment') prior to infection...
April 27, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28445714/the-toll-like-receptor-2-agonist-pam3csk4-is-neuroprotective-after-spinal-cord-injury
#20
Nicole S Stivers, Nicolas Pelisch, Ben C Orem, Joshua Williams, Jacqueline M Nally, David P Stirling
Microglia/macrophage activation and recruitment following spinal cord injury (SCI) is associated with both detrimental and reparative functions. Stimulation of the innate immune receptor Toll-like receptor-2 (TLR2) has shown to be beneficial following SCI, and it increases axonal regeneration following optic nerve crush. However, the mechanism(s) remain unclear. As microglia express high levels of TLR2, we hypothesized that modulating the microglial response to injury using a specific TLR2 agonist, Pam3CSK4, would prevent secondary-mediated white matter degeneration following SCI...
August 2017: Experimental Neurology
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