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Nicolina E Savvaidou, Lazaros C Triarhou
Professor Emil Redlich (1866-1930) of the University of Vienna was born 150 years ago. Raised in a humble environment, he became an eminent researcher and neurology scholar, and succeeded in laying some of the key foundations of neuroanatomy and neuropathology. His name is linked to medical eponyms that define the dorsal root entry zone into the spinal cord, epidemic disseminated encephalomyelitis, narcolepsy, senile plaques and dementia. As its first director, he managed to organize the Maria-Theresien-Schlössel into a first-class neuropsychiatric hospital...
October 21, 2016: European Neurology
Shin-Ichi Inaba, Maki Goto, Kaoru Tanaka-Takanaka, Hisako Tanaka, Wataru Tomisato, Hiroshi Yuita, Hiromi Doi-Komuro, Ryotaku Inoue, Keiko Oshima, Takashi Kagari, Takaichi Shimozato, Takashi Izumi
The pharmacokinetic (PK) and pharmacodynamic (PD) modeling was conducted for the reduction of peripheral lymphocytes after oral administration of CS-0777 to healthy rats, monkeys and experimental autoimmune encephalomyelitis (EAE) induced rats. M1, the phosphorylated active metabolite of CS-0777, is a selective sphingosine 1-phosphate receptor-1 modulator. A linear one-and two-compartment model with reversible metabolism process characterized the time courses of CS-0777 and M1 concentrations in rats and monkeys, respectively...
October 20, 2016: Biopharmaceutics & Drug Disposition
K Kasarełło, A Szczepankowska, B Kwiatkowska-Patzer, A W Lipkowski, R Gadamski, D Sulejczak, M Łachwa, M Biały, J Bardowski
Multiple sclerosis (MS) is a human autoimmune neurodegenerative disease with an unknown etiology. Despite various therapies, there is no effective cure for MS. Since the mechanism of the disease is based on autoreactive T-cell responses directed against myelin antigens, oral tolerance is a promising approach for the MS treatment. Here, the experiments were performed to assess the impact of oral administration of recombinant Lactococcus lactis producing encephalogenic fragments of three myelin proteins: myelin basic protein, proteolipid protein, and myelin oligodendrocyte glycoprotein, on neuroimmunological changes in rats with experimental allergic encephalomyelitis (EAE) - an animal model of MS...
2016: Folia Neuropathologica
W Oliver Tobin, Chiara Costanzi, Yong Guo, Joseph E Parisi, Stephen D Weigand, Claudia F Lucchinetti
BACKGROUND: The spectrum of central nervous system-idiopathic inflammatory demyelinating disease (CNS-IIDD) in the elderly is uncertain. OBJECTIVE: To describe the clinical, radiological, and pathological features of a cohort of 30 pathologically proven CNS-IIDD patients ⩾65 years. METHODS: Elderly multiple sclerosis (MS)/clinically isolated syndrome (CIS) patients were compared to a cohort of 125 patients with pathologically proven MS/CIS and symptom onset <65 years...
October 19, 2016: Multiple Sclerosis: Clinical and Laboratory Research
Dusanka Skundric
This overview is aimed at reevaluating fundamental approaches of current MS therapies with focus being placed on their targeted underlying immune, molecular and cellular mechanisms. Currently used therapies are discussed in regard to their mechanisms of action, clinical accomplishments and unwanted side effects and complications. Special emphasis is given to current disease modifying therapies (DMT) and their actions at immune mechanisms of disease. Effects on DMT on CD4+Th1 cells and related cytokine and signaling pathways are discussed in more detail...
October 18, 2016: Central Nervous System Agents in Medicinal Chemistry
Erika M Palmieri, Alessio Menga, Aurore Lebrun, Douglas C Hooper, D Allan Butterfield, Massimiliano Mazzone, Alessandra Castegna
AIMS: Microglial cells are brain resident macrophages engaged in surveillance and maintained in a constant state of relative inactivity. However, their involvement in autoimmune diseases indicates that in pathological conditions microglia gain an inflammatory phenotype. The mechanisms underlying this change in the microglial phenotype are still unclear. Since metabolism is an important modulator of immune cell function, we focused our attention on glutamine synthetase (GS), a modulator of the response to LPS-activation in other cell types, which is expressed by microglia...
October 19, 2016: Antioxidants & Redox Signaling
Ke-Wei Tian, Fan Zhang, Hong Jiang, Beibei Wang, Shu Han
Multiple sclerosis (MS) is a chronic neurological disorder that affects the central nervous system (CNS), and results in CNS inflammation and damage to myelin. In this study, we examined the possible synergistic effects of C16, angiopoietin-1 (Ang-1) and regeneration gene protein 2 (Reg-2) in alleviating inflammation in an acute experimental autoimmune encephalomyelitis (EAE) model. We employed multiple histological, morphological and iconographic assays to examine the effect of those drugs on disease onset, clinical scores and behavioral deficits...
October 19, 2016: Journal of Anatomy
Michael M Neeki, Christine Au, Aurora Richard, Carlos Peace, Sharon Jaques, Jens Johansson
PURPOSE: We aimed to describe a case of an incarcerated adolescent with acute disseminated encephalomyelitis (ADEM) presenting as acute psychosis. METHODS: This was a retrospective case report followed with chart and literature review. MAIN FINDINGS: An adolescent with ADEM presented with drastic behavior and personality changes that led to her incarceration for serious charges. Acute disseminated encephalomyelitis leads to neuropsychiatric effects and can be seen with magnetic resonance imaging as a large mass effect that may result in a poor prognosis...
October 4, 2016: Pediatric Emergency Care
Ragnhild Reehorst Lereim, Eystein Oveland, Yichuan Xiao, Øivind Torkildsen, Stig Wergeland, Kjell-Morten Myhr, Shao-Cong Sun, Frode S Berven
The ubiquitin ligase Peli1 has previously been suggested as a potential treatment target in multiple sclerosis. In the multiple sclerosis disease model, experimental autoimmune encephalomyelitis, Peli1 knock-out led to less activated microglia and less inflammation in the central nervous system. Despite being important in microglia, Peli1 expression has also been detected in glial and neuronal cells. In the present study the overall brain proteomes of Peli1 knock-out mice and wild-type mice were compared prior to experimental autoimmune encephalomyelitis induction, at onset of the disease and at disease peak...
September 2016: Journal of Proteomics & Bioinformatics
Lorenzo Massimi, Michela Fratini, Inna Bukreeva, Francesco Brun, Alberto Mittone, Gaetano Campi, Raffaele Spanò, Milena Mastrogiacomo, Nicole Kerlero de Rosbo, Alberto Bravin, Antonio Uccelli, Alessia Cedola
High resolution Synchrotron-based X-ray Phase Contrast Tomography (XPCT) allows the simultaneous detection of three dimensional neuronal and vascular networks without using contrast agents or invasive casting preparation. We show and discuss the different features observed in reconstructed XPCT volumes of the ex vivo mouse spinal cord in the lumbo-sacral region, including motor neurons and blood vessels. We report the application of an intensity-based segmentation method to detect and quantitatively characterize the modification in the vascular networks in terms of reduction in experimental visibility...
October 12, 2016: Physica Medica: PM
Pietro Maggi, Pascal Sati, Luca Massacesi
Magnetic resonance imaging (MRI) is an invaluable tool for the diagnosis and monitoring of patients with multiple sclerosis (MS) as well as for the study of the disease pathophysiology. Because of its strong clinical, radiological and histopathological similarities with the human disease, experimental autoimmune encephalomyelitis (EAE) in the common marmoset has been studied more intensively over the past several years. Here, we review the current knowledge on MRI in the marmoset EAE, and we outline the physiopathological significance and translational values of these studies with respect to MS...
October 8, 2016: Journal of Neuroimmunology
Y Yamaguchi, H Torisu, R Kira, Y Ishizaki, Y Sakai, M Sanefuji, T Ichiyama, A Oka, T Kishi, S Kimura, M Kubota, J Takanashi, Y Takahashi, H Tamai, J Natsume, S Hamano, S Hirabayashi, Y Maegaki, M Mizuguchi, K Minagawa, H Yoshikawa, J Kira, S Kusunoki, T Hara
OBJECTIVE: To investigate the clinical and epidemiologic features of pediatric acquired demyelinating syndromes (ADS) of the CNS in Japan. METHODS: We conducted a nationwide survey and collected clinical data on children with ADS aged 15 years or younger, who visited hospitals between 2005 and 2007. RESULTS: Among 977 hospitals enrolled, 723 (74.0%) responded to our inquiries and reported a total of 439 patients as follows: 244 with acute disseminated encephalomyelitis (ADEM), 117 with multiple sclerosis (MS), 14 with neuromyelitis optica (NMO), and 64 with other ADS...
October 14, 2016: Neurology
Anna K Taylor, Maria Loades, Amberly Lc Brigden, Simon M Collin, Esther Crawley
BACKGROUND: Paediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) has a prevalence of 0.4-2.4% and is defined as 'generalised disabling fatigue persisting after routine tests and investigations have failed to identify an obvious underlying cause'. One-third of young people with CFS/ME have probable depression. Little is known about why depression develops, the relationship between depression and CFS/ME, or what treatment might be helpful. METHODS: We conducted nine semi-structured interviews with young people with CFS/ME (aged 13-17 years, 8/9 female) and probable depression, covering perceived causes of depression, the relationship between CFS/ME and depression, and treatment strategies...
October 14, 2016: Clinical Child Psychology and Psychiatry
Caroline Stienne, Michaël F Michieletto, Mehdi Benamar, Nadège Carrié, Isabelle Bernard, Xuan-Hung Nguyen, Yannick Lippi, Fanny Duguet, Roland S Liblau, Stephen M Hedrick, Abdelhadi Saoudi, Anne S Dejean
The transcription factor Foxo3 plays a crucial role in myeloid cell function but its role in lymphoid cells remains poorly defined. Here, we have shown that Foxo3 expression was increased after T cell receptor engagement and played a specific role in the polarization of CD4(+) T cells toward pathogenic T helper 1 (Th1) cells producing interferon-γ (IFN-γ) and granulocyte monocyte colony stimulating factor (GM-CSF). Consequently, Foxo3-deficient mice exhibited reduced susceptibility to experimental autoimmune encephalomyelitis...
October 1, 2016: Immunity
Melissa L Barker-Haliski, Taylor D Heck, E Jill Dahle, Fabiola Vanegas, Timothy H Pruess, Karen S Wilcox, H Steve White
OBJECTIVE: Infection with Theiler's murine encephalomyelitis virus (TMEV) in C57Bl/6J mice induces acute seizures and development of spontaneous recurrent seizures and behavioral comorbidities weeks later. The present studies sought to determine whether acute therapeutic intervention with an anti-inflammatory-based approach could prevent or modify development of TMEV-induced long-term behavioral comorbidities. Valproic acid (VPA), in addition to its prototypical anticonvulsant properties, inhibits histone deacetylase (HDAC) activity, which may alter expression of the inflammasome...
October 14, 2016: Epilepsia
Ellen Brady, Julia Segar, Caroline Sanders
BACKGROUND: The ethics of research into online communities is a long-debated issue, with many researchers arguing that open-access discussion groups are publically accessible data and do not require informed consent from participants for their use for research purposes. However, it has been suggested that there is a discrepancy between the perceived and actual privacy of user-generated online content by community members. OBJECTIVE: There has been very little research regarding how privacy is experienced and enacted online...
October 13, 2016: Journal of Medical Internet Research
Thangavelu Soundara Rajan, Sabrina Giacoppo, Oriana Trubiani, Francesca Diomede, Adriano Piattelli, Placido Bramanti, Emanuela Mazzon
Conditioned medium derived from mesenchymal stem cells (MSCs) shows immunomodulatory and neuroprotective effects in preclinical models. Given the difficulty to harvest MSCs from bone marrow and adipose tissues, research has been focused to find alternative resources for MSCs, such as oral-derived tissues. Recently, we have demonstrated the protective effects of MSCs obtained from healthy human periodontal ligament tissue (hPDLSCs) in murine experimental autoimmune encephalomyelitis model. In the present in vitro study, we have investigated the immunomodulatory and neuroprotective effects of conditioned medium obtained from hPDLSCs of Relapsing Remitting- Multiple sclerosis (RR-MS) patients on NSC34 mouse motoneurons stimulated with lipopolysaccharide (LPS)...
October 11, 2016: Experimental Cell Research
Kerstin Renner, Sonja Hellerbrand, Fabian Hermann, Christine Riedhammer, Yvonne Talke, Gabriela Schiechl, Manuel Rodriguez Gomez, Simone Kutzi, Dagmar Halbritter, Nicole Goebel, Hilke Brühl, Robert Weissert, Matthias Mack
Little is known about the role of IL-3 in multiple sclerosis (MS) in humans and in experimental autoimmune encephalomyelitis (EAE). Using myelin oligodendrocyte glycoprotein (MOG) peptide-induced EAE, we show that CD4(+) T cells are the main source of IL-3 and that cerebral IL-3 expression correlates with the influx of T cells into the brain. Blockade of IL-3 with monoclonal antibodies, analysis of IL-3 deficient mice, and adoptive transfer of leukocytes demonstrate that IL-3 plays an important role for development of clinical symptoms of EAE, for migration of leukocytes into the brain, and for cerebral expression of adhesion molecules and chemokines...
October 6, 2016: JCI Insight
Jennifer N Hahn, Deepak K Kaushik, Manoj K Mishra, Jianxiong Wang, Claudia Silva, V Wee Yong
Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is a transmembrane glycoprotein that is upregulated on leukocytes in active lesions in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Administration of anti-EMMPRIN Abs reduces the severity of EAE. Minocycline is a tetracycline antibiotic with immune-modulatory properties that decreases the severity of EAE; it was recently found to attenuate the conversion from a first demyelinating event to clinically definite MS in a phase III trial...
October 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Annie C Bowles, Amy L Strong, Rachel M Wise, Robert C Thomas, Brittany Y Gerstein, Maria F Dutreil, Ryan S Hunter, Jeffrey M Gimble, Bruce A Bunnell
Multiple sclerosis (MS) is a common neurodegenerative disease and remains an unmet clinical challenge. In MS, an autoimmune response leads to immune cell infiltration, inflammation, demyelination, and lesions in central nervous system (CNS) tissues resulting in tremors, fatigue, and progressive loss of motor function. These pathologic hallmarks are effectively reproduced in the murine experimental autoimmune encephalomyelitis (EAE) model. The stromal vascular fraction (SVF) of adipose tissue is composed of adipose-derived stromal/stem cells (ASC), adipocytes, and various leukocytes...
October 12, 2016: Stem Cells
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