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https://www.readbyqxmd.com/read/27904491/intravenous-transplantation-of-mouse-embryonic-stem-cells-attenuates-demyelination-in-an-icr-outbred-mouse-model-of-demyelinating-diseases
#1
Kidsadagon Pringproa, Anucha Sathanawongs, Chananthida Khamphilai, Sarocha Sukkarinprom, Apichart Oranratnachai
Induction of demyelination in the central nervous system (CNS) of experimental mice using cuprizone is widely used as an animal model for studying the pathogenesis and treatment of demyelination. However, different mouse strains used result in different pathological outcomes. Moreover, because current medicinal treatments are not always effective in multiple sclerosis patients, so the study of exogenous cell transplantation in an animal model is of great importance. The aims of the present study were to establish an alternative ICR outbred mouse model for studying demyelination and to evaluate the effects of intravenous cell transplantation in the present developed mouse model...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27894396/ellagic-acid-ameliorates-cuprizone-induced-acute-cns-inflammation-via-restriction-of-microgliosis-and-down-regulation-of-ccl2-and-ccl3-pro-inflammatory-chemokines
#2
N Sanadgol, F Golab, A Mostafaie, M Mehdizadeh, M Abdollahi, M Sharifzadeh, H Ravan
Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuro-inflammatory conditions. Microglia making the innate immune system of the central nervous system (CNS) and are imperative cellular mediators of neuro-inflammatory processes. In this study, neuro-protective effects of EA on cuprizone (Cup)-induced acute CNS inflammation evaluated. C57BL/6J mice were fed with chow containing 0.2 % Cup for 3 weeks to induce acute neuro-inflammation predominantly in the corpus callosum (CC)...
October 31, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/27873367/mir-219-attenuates-demyelination-in-cuprizone-induced-demyelinated-mice-by-regulating-monocarboxylate-transporter-1
#3
Sihan Liu, Chuanlu Ren, Xuebin Qu, Xiuxiang Wu, Fuxing Dong, Yadav Kaushal Chand, Hongbin Fan, Ruiqin Yao, Deqin Geng
Remyelination is limited in patients with multiple sclerosis (MS) due to the difficulties in recruiting proliferating oligodendrocyte precursors (OPCs), the inhibition of OPC differentiation and/or maturation, and/or failure in the generation of the myelin sheath. In vitro studies have revealed that miR-219 is necessary for OPC differentiation and monocarboxylate transporter 1 (MCT1) plays a vital role in oligodendrocyte maturation and myelin synthesis. Herein, we hypothesized that miR-219 might promote oligodendrocyte differentiation and attenuate demyelination in a cuprizone (CPZ)-induced demyelinated model by regulating the expression of MCT1...
November 22, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27861886/oligodendrocyte-progenitor-cells-directly-utilize-lactate-for-promoting-cell-cycling-and-differentiation
#4
Yoshinori Ichihara, Toru Doi, Youngjae Ryu, Motoshi Nagao, Yasuhiro Sawada, Toru Ogata
Oligodendrocyte progenitor cells (OPCs) undergo marked morphological changes to become mature oligodendrocytes, but the metabolic resources for this process have not been fully elucidated. Although lactate, a metabolic derivative of glycogen, has been reported to be consumed in oligodendrocytes as a metabolite, and to ameliorate hypomyelination induced by low glucose conditions, it is not clear about the direct contribution of lactate to cell cycling and differentiation of OPCs, and the source of lactate for remyelination...
November 15, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27845252/the-connectomics-of-brain-demyelination-functional-and-structural-patterns-in-the-cuprizone-mouse-model
#5
Neele Saskia Hübner, Anna E Mechling, Hsu-Lei Lee, Marco Reisert, Thomas Bienert, Jürgen Hennig, Dominik von Elverfeldt, Laura-Adela Harsan
Connectomics of brain disorders seeks to reveal how altered brain function emerges from the architecture of cerebral networks; however the causal impact of targeted cellular damage on the whole brain functional and structural connectivity remains unknown. In the central nervous system, demyelination is typically the consequence of an insult targeted at the oligodendrocytes, the cells forming and maintaining the myelin. This triggered perturbation generates cascades of pathological events that most likely alter the brain connectome...
November 11, 2016: NeuroImage
https://www.readbyqxmd.com/read/27833805/whole-brain-ex-vivo-quantitative-mri-of-the-cuprizone-mouse-model
#6
Tobias C Wood, Camilla Simmons, Samuel A Hurley, Anthony C Vernon, Joel Torres, Flavio Dell'Acqua, Steve C R Williams, Diana Cash
Myelin is a critical component of the nervous system and a major contributor to contrast in Magnetic Resonance (MR) images. However, the precise contribution of myelination to multiple MR modalities is still under debate. The cuprizone mouse is a well-established model of demyelination that has been used in several MR studies, but these have often imaged only a single slice and analysed a small region of interest in the corpus callosum. We imaged and analyzed the whole brain of the cuprizone mouse ex-vivo using high-resolution quantitative MR methods (multi-component relaxometry, Diffusion Tensor Imaging (DTI) and morphometry) and found changes in multiple regions, including the corpus callosum, cerebellum, thalamus and hippocampus...
2016: PeerJ
https://www.readbyqxmd.com/read/27833528/gray-and-white-matter-demyelination-and-remyelination-detected-with-multimodal-quantitative-mri-analysis-at-11-7t-in-a-chronic-mouse-model-of-multiple-sclerosis
#7
Alexandra Petiet, Marie-Stéphane Aigrot, Bruno Stankoff
Myelin is a component of the nervous system that is disrupted in multiple sclerosis, resulting in neuro-axonal degeneration. The longitudinal effect of chronic cuprizone-induced demyelination was investigated in the cerebral gray and white matter of treated mice and the spontaneous remyelination upon treatment interruption. Multimodal Magnetic Resonance Imaging and a Cryoprobe were used at 11.7T to measure signal intensity ratios, T2 values and diffusion metrics. The results showed significant and reversible modifications in white matter and gray matter regions such as in the rostral and caudal corpus callosum, the external capsule, the cerebellar peduncles, the caudate putamen, the thalamus, and the somatosensory cortex of treated mice...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27829467/intracerebral-transplantation-of-interleukin-13-producing-mesenchymal-stem-cells-limits-microgliosis-oligodendrocyte-loss-and-demyelination-in-the-cuprizone-mouse-model
#8
Debbie Le Blon, Caroline Guglielmetti, Chloé Hoornaert, Alessandra Quarta, Jasmijn Daans, Dearbhaile Dooley, Evi Lemmens, Jelle Praet, Nathalie De Vocht, Kristien Reekmans, Eva Santermans, Niel Hens, Herman Goossens, Marleen Verhoye, Annemie Van der Linden, Zwi Berneman, Sven Hendrix, Peter Ponsaerts
BACKGROUND: Promoting the neuroprotective and repair-inducing effector functions of microglia and macrophages, by means of M2 polarisation or alternative activation, is expected to become a new therapeutic approach for central nervous system (CNS) disorders in which detrimental pro-inflammatory microglia and/or macrophages display a major contribution to the neuropathology. In this study, we present a novel in vivo approach using intracerebral grafting of mesenchymal stem cells (MSC) genetically engineered to secrete interleukin 13 (IL13-MSC)...
November 9, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27792289/multiple-sclerosis-animal-models-a-clinical-and-histopathological-perspective
#9
REVIEW
Markus Kipp, Stella Nyamoya, Tanja Hochstrasser, Sandra Amor
There is a broad consensus that multiple sclerosis (MS) represents more than an inflammatory disease: it harbors several characteristic aspects of a classical neurodegenerative disorder, i.e. damage to axons, synapses and nerve cell bodies. While we are equipped with appropriate therapeutic options to prevent immune-cell driven relapses, effective therapeutic options to prevent the progressing neurodegeneration are still missing. In this review article, we will discuss to what extent pathology of the progressive disease stage can be modeled in MS animal models...
October 28, 2016: Brain Pathology
https://www.readbyqxmd.com/read/27764518/administration-of-vitamin-d3-induces-cnpase-and-myelin-oligodendrocyte-glycoprotein-expression-in-the-cerebral-cortex-of-the-murine-model-of-cuprizone-induced-demyelination
#10
F Mashayekhi, Z Salehi
In the central nervous system (CNS) the main proteins of myelin are proteolipid protein (PLP), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG) and CNPase. Myelin oligodendrocyte glycoprotein is a minor component of the myelin sheath, but is an important autoantigen linked to the pathogenesis of multiple sclerosis (MS). CNPase is expressed exclusively by oligodendrocytes in the CNS, and the appearance of CNPase seems to be one of the earliest events of oligodendrocyte differentiation and myelination...
2016: Folia Neuropathologica
https://www.readbyqxmd.com/read/27714696/the-role-of-galectin-3-from-oligodendroglial-differentiation-and-myelination-to-demyelination-and-remyelination-processes-in-a-cuprizone-induced-demyelination-model
#11
H C Hoyos, Mariel Marder, R Ulrich, V Gudi, M Stangel, G A Rabinovich, L A Pasquini, J M Pasquini
The aim of this work was to combine our previously published results with our new data to show how galectin-3 (Gal-3) controls myelin integrity and function, promotes oligodendroglial cell differentiation, and regulates microglial responses to limit cuprizone- (CPZ)-induced demyelination and foster remyelination. In this study, 8-week-old Gal-3-deficient (Lgals3 (-/-)) and wild type (WT) mice were fed a diet containing 0.2 % CPZ w/w for 6 weeks, after which CPZ was withdrawn in order to allow remyelination...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27713953/myricetin-alleviates-cuprizone-induced-behavioral-dysfunction-and-demyelination-in-mice-by-nrf2-pathway
#12
Qianying Zhang, Zhike Li, Shuangchan Wu, Xiaofei Li, Ying Sang, Jian Li, Yunhui Niu, Hong Ding
Multiple sclerosis (MS) is a demyelinating disease occurring in the central nervous system. In the present study, we evaluated the function of myricetin on the alleviation of behavioral dysfunction and myelin protection in the cuprizone-induced demyelination model. Mice were daily fed with fodder including 0.2% cuprizone and were administrated myricetin (100 mg kg(-1)) by gavage administration for 5 weeks. The treatment of myricetin ameliorated hyper-locomotion and behavior impairment induced by cuprizone toxicity...
October 12, 2016: Food & Function
https://www.readbyqxmd.com/read/27699230/a-cord-blood-monocyte-derived-cell-therapy-product-accelerates-brain-remyelination
#13
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/27685637/interleukin-13-immune-gene-therapy-prevents-cns-inflammation-and-demyelination-via-alternative-activation-of-microglia-and-macrophages
#14
Caroline Guglielmetti, Debbie Le Blon, Eva Santermans, Angelica Salas-Perdomo, Jasmijn Daans, Nathalie De Vocht, Disha Shah, Chloé Hoornaert, Jelle Praet, Jurgen Peerlings, Firat Kara, Christian Bigot, Zhenhua Mai, Herman Goossens, Niel Hens, Sven Hendrix, Marleen Verhoye, Anna M Planas, Zwi Berneman, Annemie van der Linden, Peter Ponsaerts
Detrimental inflammatory responses in the central nervous system are a hallmark of various brain injuries and diseases. With this study we provide evidence that lentiviral vector-mediated expression of the immune-modulating cytokine interleukin 13 (IL-13) induces an alternative activation program in both microglia and macrophages conferring protection against severe oligodendrocyte loss and demyelination in the cuprizone mouse model for multiple sclerosis (MS). First, IL-13 mediated modulation of cuprizone induced lesions was monitored using T2 -weighted magnetic resonance imaging and magnetization transfer imaging, and further correlated with quantitative histological analyses for inflammatory cell influx, oligodendrocyte death, and demyelination...
September 29, 2016: Glia
https://www.readbyqxmd.com/read/27641725/activation-of-the-astrocytic-nrf2-are-system-ameliorates-the-formation-of-demyelinating-lesions-in-a-multiple-sclerosis-animal-model
#15
T Draheim, A Liessem, M Scheld, F Wilms, M Weißflog, B Denecke, T W Kensler, A Zendedel, C Beyer, M Kipp, C J Wruck, A Fragoulis, T Clarner
Oxidative stress critically contributes to the pathogenesis of a variety of neurodegenerative diseases such as multiple sclerosis. Astrocytes are the main regulators of oxidative homeostasis in the brain and dysregulation of these cells likely contributes to the accumulation of oxidative damage. The nuclear factor erythroid 2-related factor 2 (Nrf2) is the main transcriptional regulator of the anti-oxidant stress defense. In this study, we elucidate the effects of astrocytic Nrf2-activation on brain-intrinsic inflammation and lesion development...
September 19, 2016: Glia
https://www.readbyqxmd.com/read/27613805/social-isolation-impairs-remyelination-in-mice-through-modulation-of-il-6
#16
Manabu Makinodan, Daisuke Ikawa, Yuki Miyamoto, Junji Yamauchi, Kazuhiko Yamamuro, Yasunori Yamashita, Michihiro Toritsuka, Sohei Kimoto, Kazuki Okumura, Takahira Yamauchi, Shin-Ichi Fukami, Hiroki Yoshino, Akio Wanaka, Toshifumi Kishimoto
Recent studies have revealed that social experience affects myelination. These findings have important implications for disorders that feature abnormal myelination, such as multiple sclerosis (MS), as previous studies have shown that psychosocial stress exacerbates the pathobiology of MS. However, most studies have focused on psychosocial stress during the demyelination phase of MS and have not investigated the effects of social experience on remyelination. Thus, the current study sought to determine whether social experience can alter remyelination after myelin depletion...
December 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27596241/the-crucial-role-of-erk2-in-demyelinating-inflammation-in-the-central-nervous-system
#17
Rentaro Okazaki, Toru Doi, Kentaro Hayakawa, Kazuhito Morioka, Osamu Imamura, Kunio Takishima, Makoto Hamanoue, Yasuhiro Sawada, Motoshi Nagao, Sakae Tanaka, Toru Ogata
BACKGROUND: Brain inflammation is a crucial component of demyelinating diseases such as multiple sclerosis. Although the initiation of inflammatory processes by the production of cytokines and chemokines by immune cells is well characterized, the processes of inflammatory aggravation of demyelinating diseases remain obscure. Here, we examined the contribution of Erk2, one of the isoforms of the extracellular signal-regulated kinase, to demyelinating inflammation. METHODS: We used the cuprizone-induced demyelinating mouse model...
2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27592741/acute-axonal-damage-in-three-different-murine-models-of-multiple-sclerosis-a-comparative-approach
#18
Katharina Marie Höflich, Cordian Beyer, Tim Clarner, Christoph Schmitz, Stella Nyamoya, Markus Kipp, Tanja Hochstrasser
Axonal damage has been identified as a significant contributor to permanent clinical disability in multiple sclerosis. In the context of demyelinating disorders, this destructive event can be the result of inflammation, demyelination and/or the activation of innate defense cells such as microglia or monocytes. The relative contribution of each of these variables to acute axonal injury is, however, unknown. In the present study, we compared the extent of acute axonal damage in three different murine demyelination models using anti-amyloid precursor protein (APP) immunohistochemistry...
November 1, 2016: Brain Research
https://www.readbyqxmd.com/read/27590316/thrombomodulin-dependent-protein-c-activation-is-required-for-mitochondrial-function-and-myelination-in-the-central-nervous-system
#19
J Wolter, L Schild, F Bock, A Hellwig, I Gadi, M M Al-Dabet, S Ranjan, R Rönicke, P P Nawroth, K-U Petersen, C Mawrin, K Shahzad, B Isermann
: Essentials The role of protein C (PC) activation in experimental autoimmune encephalitis (EAE) is unknown. PC activation is required for mitochondrial function in the central nervous system. Impaired PC activation aggravates EAE, which can be compensated for by soluble thrombomodulin. Protection of myelin by activated PC or solulin is partially independent of immune-modulation. SUMMARY: Background Studies with human samples and in rodents established a function of coagulation proteases in neuro-inflammatory demyelinating diseases (e...
September 3, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27580304/cyclin-dependent-kinase-inhibitor-flavopiridol-promotes-remyelination-in-a-cuprizone-induced-demyelination-model
#20
Guiyun Mi, Yunyun Gao, Shuai Liu, Enmao Ye, Yanyan Li, Xiao Jin, Hongju Yang, Zheng Yang
The cuprizone (CPZ) model has been widely used for the studies of de-and remyelination. The CPZ-exposed mice show oligodendrocyte precursor cells (OPCs) increase and mature oligodendrocytes decrease, suggesting an imbalance between proliferation and differentiation of OPCs. In the first experiment of this study, we examined the expression of cell cycle related genes in brains of mice following CPZ administration for 5 weeks by means of microarray assay. In addition, we performed a double labeling of BrdU and Ki-67 to calculate cell cycle exit index in the mice...
October 17, 2016: Cell Cycle
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