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https://www.readbyqxmd.com/read/28737509/astrocytic-tight-junctions-control-inflammatory-cns-lesion-pathogenesis
#1
Sam Horng, Anthony Therattil, Sarah Moyon, Alexandra Gordon, Karla Kim, Azeb Tadesse Argaw, Yuko Hara, John N Mariani, Setsu Sawai, Per Flodby, Edward D Crandall, Zea Borok, Michael V Sofroniew, Candice Chapouly, Gareth R John
Lesions and neurologic disability in inflammatory CNS diseases such as multiple sclerosis (MS) result from the translocation of leukocytes and humoral factors from the vasculature, first across the endothelial blood-brain barrier (BBB) and then across the astrocytic glia limitans (GL). Factors secreted by reactive astrocytes open the BBB by disrupting endothelial tight junctions (TJs), but the mechanisms that control access across the GL are unknown. Here, we report that in inflammatory lesions, a second barrier composed of reactive astrocyte TJs of claudin 1 (CLDN1), CLDN4, and junctional adhesion molecule A (JAM-A) subunits is induced at the GL...
July 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28713781/the-metalloprotease-mpr1-engages-annexina2-to-promote-the-transcytosis-of-fungal-cells-across-the-blood-brain-barrier
#2
Sarisa Na Pombejra, Michelle Salemi, Brett S Phinney, Angie Gelli
Eukaryotic pathogens display multiple mechanisms for breaching the blood-brain barrier (BBB) and invading the central nervous system (CNS). Of the fungal spp., that cause disease in mammals, only some cross brain microvascular endothelial cells which constitute the BBB, and invade the brain. Cryptococcus neoformans, the leading cause of fungal meningoencephalitis, crosses the BBB directly by transcytosis or by co-opting monocytes. We previously determined that Mpr1, a secreted fungal metalloprotease, facilitates association of fungal cells to brain microvascular endothelial cells and we confirmed that the sole expression of CnMPR1 endowed S...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28701209/alantolactone-a-natural-sesquiterpene-lactone-has-potent-antitumor-activity-against-glioblastoma-by-targeting-ikk%C3%AE-kinase-activity-and-interrupting-nf-%C3%AE%C2%BAb-cox-2-mediated-signaling-cascades
#3
Xun Wang, Zhenlong Yu, Chao Wang, Wei Cheng, Xiangge Tian, Xiaokui Huo, Yan Wang, Chengpeng Sun, Lei Feng, Jinshan Xing, Yulong Lan, Dongdong Sun, Qingjuan Hou, Baojing Zhang, Xiaochi Ma, Bo Zhang
BACKGROUND: Glioblastoma multiforme (GBM) is one of the most refractory and palindromic central nervous system (CNS) neoplasms, and current treatments have poor effects in GBM patients. Hence, the identification of novel therapeutic targets and the development of effective treatment strategies are essential. Alantolactone (ATL) has a wide range of pharmacological activities, and its anti-tumor effect is receiving increasing attention. However, the molecular mechanism underlying the anti-GBM activity of ATL remains poorly understood...
July 12, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28687012/value-of-quantitative-magnetic-resonance-imaging-t1-relaxometry-in-predicting-contrast-enhancement-in-glioblastoma-patients
#4
Elke Hattingen, Andreas Müeller, Alina Jurcoane, Burkhard Mädler, Philip Ditter, Hans Schild, Ulrich Herrlinger, Martin Glas, Sied Kebir
The repetitive usage of gadolinium-based contrast agents (GBCA) is critical for magnetic resonance imaging (MRI) evaluation of tumor burden in glioblastoma patients. It is also a crucial tool for determination of radiographical response to treatment. GBCA injection, however, comes with a 2.4% rate of adverse events including life-threatening conditions such as nephrogenic systemic fibrosis (NSF). Moreover, GBCA have been shown to be deposited in brain tissue of patients even with an intact blood-brain barrier (BBB)...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28652141/andrographolide-loaded-nanoparticles-for-brain-delivery-formulation-characterisation-and-in-vitro-permeability-using-hcmec-d3-cell-line
#5
Clizia Guccione, Mouhssin Oufir, Vieri Piazzini, Daniela Elisabeth Eigenmann, Evelyn Andrea Jähne, Volha Zabela, Maria Teresa Faleschini, Maria Camilla Bergonzi, Martin Smiesko, Matthias Hamburger, Anna Rita Bilia
Andrographolide (AG) is a major diterpenoid of the Asian medicinal plant Andrographis paniculata which has shown exciting pharmacological potential for the treatment of inflammation-related pathologies including neurodegenerative disorders. Conversely, the low bioavailability of AG still represents a limiting factor for its use. To overcome these limitations, AG was loaded into human serum albumin based nanoparticles (HSA NPs) and poly ethylcyanoacrylate nanoparticles (PECA NPs). HSA NPs were prepared by thermal (HSAT AG NPs) and chemical cross-linking (HSAC AG NPs), while PECA AG NPs were produced by emulsion-polymerization...
June 23, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28620801/fty720-attenuates-infection-induced-enhancement-of-a%C3%AE-accumulation-in-app-ps1-mice-by-modulating-astrocytic-activation
#6
Róisín M McManus, Orla M Finucane, Mieszko M Wilk, Kingston H G Mills, Marina A Lynch
It is well established that infection has a significant detrimental effect on patients with Alzheimer's disease (AD), accelerating cognitive decline and, even in healthy ageing individuals, increasing amyloid-β (Aβ) accumulation in the brain. In animal models of AD infection can also cause damage, with evidence of increased neuroinflammation, amyloid pathology and deterioration of cognitive function. These changes are against a backdrop of an age- and AD-related increase in susceptibility to infection. Here we set out to determine whether FTY720, a molecule that binds sphingosine-1-phosphate (S1P) receptors and with known immunosuppressant effects mediating its therapeutic action in multiple sclerosis (MS), might modulate the impact of infection in a mouse model of AD...
June 15, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28619424/cerebrospinal-fluid-and-serum-levels-of-interleukin-8-in-patients-with-multiple-sclerosis-and-its-correlation-with-q-albumin
#7
Z Matejčíková, J Mareš, V Sládková, T Svrčinová, J Vysloužilová, J Zapletalová, P Kaňovský
INTRODUCTION: Multiple sclerosis (MS) is an inflammatory-demyelinating disease of the central nervous system (CNS). Autoimmune inflammation is common in the early stages of MS and is followed by neurodegenerative processes. The result of these changes is axon and myelin breakdown. The paraclinical examination methods are an important part of the diagnostic process. Magnetic resonance imaging of the brain and the cervical spinal cord and an examination of cerebrospinal fluid (CSF) are common paraclinical examinations...
May 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28615922/influence-of-circulating-endothelin-1-and-asymmetric-dimethylarginine-on-whole-brain-circulation-time-in-multiple-sclerosis
#8
Lucia Monti, Lucia Morbidelli, Lorenzo Bazzani, Alessandro Rossi
Blood-brain barrier (BBB) breakdown, inflammatory and immune cell activation, and chronic cerebral hypoperfusion are features of multiple sclerosis (MS). The aim is to determine the influence of endothelin-1 (ET1) and asymmetric dimethylarginine (ADMA) on cerebral circulation time (CCT) in patients with MS. In all, 64 patients with MS (39 relapsing-remitting [RR]-MS; 25 secondary progressive [SP]-MS subtype) and 37 controls (C) were studied. Cerebral circulation time was obtained by angiography. Plasmatic ET1 and ADMA were measured by enzyme-linked immunosorbent assay...
2017: Biomarker Insights
https://www.readbyqxmd.com/read/28605675/isosteroidal-alkaloids-as-potent-dual-binding-site-inhibitors-of-both-acetylcholinesterase-and-butyrylcholinesterase-from-the-bulbs-of-fritillaria-walujewii
#9
Yu-Ming Liu, Ya-Dong Feng, Xi Lu, Jian-Bing Nie, Wei Li, Li-Ning Wang, Li-Jun Tian, Qing-Hua Liu
Five new isosteroidal alkaloids, walujewine A (1), walujewine B (4), walujewine C (5), walujewine D (6), walujewine E (10) were isolated from the bulbs of Fritillaria walujewii together with seven known isosteroidal alkaloids (2, 3, 7-9, 11, 12). Their structures were elucidated on the basis of IR, ESI-MS, HR-ESI-MS, 1D and 2D NMR spectroscopic data analyses and single-crystal X-ray diffraction. All the isolates were tested for ChE inhibiting activity by the Ellman's method. Compounds 3-5 and 8-10 were potent dual AChE-BChE inhibitors, and compound 1 showed highly selective AChE inhibition...
September 8, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28601415/brain-autoimmunity-and-intestinal-microbiota-100-trillion-game-changers
#10
REVIEW
Hartmut Wekerle
T cells play a critical role in autoimmune diseases in the brain, particularly in multiple sclerosis (MS). Since T cells are normally prevented from crossing the blood-brain barrier (BBB), autoimmunity requires prior activation of naturally occurring autoreactive T cells in peripheral tissue. Recently, a critical role for the microbiota in this activation process has emerged. Here, we review the role of gut-associated lymphoid tissues (GALT) as a major site for the phenotypic changes that allow the migration of autoreactive T cells to the brain...
July 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28596825/kv1-3-channel-blocker-imktx88-maintains-blood-brain-barrier-in-experimental-autoimmune-encephalomyelitis
#11
Jie Huang, Song Han, Qi Sun, Yipeng Zhao, Junchen Liu, Xiaolu Yuan, Wenqian Mao, Biwen Peng, Wanhong Liu, Jun Yin, Xiaohua He
BACKGROUND: Disruption of blood-brain barrier (BBB) and subsequent infiltration of auto-reactive T lymphocytes are major characteristics of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Kv1.3 channel blockers are demonstrated potential therapeutic effects on MS patients and EAE models, maybe via reducing activation of T cells. However, it remains to be explored whether Kv1.3 channel blockers maintain integrity of BBB in MS model. RESULTS: In this study, ImKTx88, a highly selective Kv1...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28581635/targeted-unlabeled-mrm-analysis-of-cell-markers-for-the-study-of-sample-heterogeneity-in-isolated-rat-brain-cortical-microvessels
#12
David Gomez-Zepeda, Catarina Chaves, Meryam Taghi, Philippe Sergent, Wang-Qing Liu, Cerina Chhuon, Michel Vidal, Martin Picard, Elizabeth Thioulouse, Isabelle Broutin, Ida-Chiara Guerrera, Jean-Michel Scherrmann, Yannick Parmentier, Xavier Decleves, Marie-Claude Menet
LC-MS/MS-based targeted absolute protein quantification (in fmol of the analyte protein per μg of total protein) is employed for the molecular characterization of the blood brain barrier (BBB) using isolated brain microvessels. Nevertheless, the heterogeneity of the sample regarding the levels of different cells co-isolated within the microvessels and BSA contamination (from buffers) are not always evaluated. We developed an unlabeled targeted LC-MS/MS method to survey the levels of endothelial cells (ECs), astrocytes and pericytes, as well as BSA contaminant in rat cortical microvessels...
June 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28578388/antibody-blockade-of-clec12a-delays-eae-onset-and-attenuates-disease-severity-by-impairing-myeloid-cell-cns-infiltration-and-restoring-positive-immunity
#13
Divya Sagar, Narendra P Singh, Rashida Ginwala, Xiaofang Huang, Ramila Philip, Mitzi Nagarkatti, Prakash Nagarkatti, Konstantin Neumann, Jürgen Ruland, Allison M Andrews, Servio H Ramirez, Zafar K Khan, Pooja Jain
The mechanism of dendritic cells (DCs) recruitment across the blood brain barrier (BBB) during neuroinflammation has been the least explored amongst all leukocytes. For cells of myeloid origin, while integrins function at the level of adhesion, the importance of lectins remains unknown. Here, we identified functions of one C-type lectin receptor, CLEC12A, in facilitating DC binding and transmigration across the BBB in response to CCL2 chemotaxis. To test function of CLEC12A in an animal model of multiple sclerosis (MS), we administered blocking antibody to CLEC12A that significantly ameliorated disease scores in MOG35-55-induced progressive, as well as PLP138-151-induced relapsing-remitting experimental autoimmune encephalomyelitis (EAE) mice...
June 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28551311/evaluation-of-pharmacokinetics-and-blood-brain-barrier-permeability-of-mitragynine-using-in-vivo-microdialysis-technique
#14
Wai Mun Kong, Zahurin Mohamed, Mohammed A Alshawsh, Zamri Chik
A microdialysis system coupled with a sensitive ultra-fast liquid chromatography-mass spectrometry (UFLC-MS) method was developed for the pharmacokinetic analysis of mitragynine in rat blood and striatum. Mitragynine is an active alkaloid of Mitragyna speciosa and has been proposed to be used for opioid withdrawal therapy. In this study, chromatographic separation was performed in a gradient elution mode with 0.1% formic acid and acetonitrile on a Zorbax Eclipse C18 column. The mass spectrometric (MS) analysis was carried out in a positive electrospray mode and mitragynine ion (m/z 399...
September 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28494768/inhibition-of-cd40-traf6-interactions-by-the-small-molecule-inhibitor-6877002-reduces-neuroinflammation
#15
Suzanne A B M Aarts, Tom T P Seijkens, Pascal J H Kusters, Susanne M A van der Pol, Barbara Zarzycka, Priscilla D A M Heijnen, Linda Beckers, Myrthe den Toom, Marion J J Gijbels, Louis Boon, Christian Weber, Helga E de Vries, Gerry A F Nicolaes, Christine D Dijkstra, Gijs Kooij, Esther Lutgens
BACKGROUND: The influx of leukocytes into the central nervous system (CNS) is a key hallmark of the chronic neuro-inflammatory disease multiple sclerosis (MS). Strategies that aim to inhibit leukocyte migration across the blood-brain barrier (BBB) are therefore regarded as promising therapeutic approaches to combat MS. As the CD40L-CD40 dyad signals via TNF receptor-associated factor 6 (TRAF6) in myeloid cells to induce inflammation and leukocyte trafficking, we explored the hypothesis that specific inhibition of CD40-TRAF6 interactions can ameliorate neuro-inflammation...
May 12, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28443093/a-novel-cervical-spinal-cord-window-preparation-allows-for-two-photon-imaging-of-t-cell-interactions-with-the-cervical-spinal-cord-microvasculature-during-experimental-autoimmune-encephalomyelitis
#16
Neda Haghayegh Jahromi, Heidi Tardent, Gaby Enzmann, Urban Deutsch, Naoto Kawakami, Stefan Bittner, Dietmar Vestweber, Frauke Zipp, Jens V Stein, Britta Engelhardt
T-cell migration across the blood-brain barrier (BBB) is a crucial step in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Two-photon intravital microscopy (2P-IVM) has been established as a powerful tool to study cell-cell interactions in inflammatory EAE lesions in living animals. In EAE, central nervous system inflammation is strongly pronounced in the spinal cord, an organ in which 2P-IVM imaging is technically very challenging and has been limited to the lumbar spinal cord...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28422748/therapeutic-inhibition-of-soluble-brain-tnf-promotes-remyelination-by-increasing-myelin-phagocytosis-by-microglia
#17
Maria Karamita, Christopher Barnum, Wiebke Möbius, Malú G Tansey, David E Szymkowski, Hans Lassmann, Lesley Probert
Multiple sclerosis (MS) is an inflammatory CNS demyelinating disease in which remyelination largely fails. Transmembrane TNF (tmTNF) and TNF receptor 2 are important for remyelination in experimental MS models, but it is unknown whether soluble TNF (solTNF), a major proinflammatory factor, is involved in regeneration processes. Here, we investigated the specific contribution of solTNF to demyelination and remyelination in the cuprizone model. Treatment with XPro1595, a selective inhibitor of solTNF that crosses the intact blood-brain barrier (BBB), in cuprizone-fed mice did not prevent toxin-induced oligodendrocyte loss and demyelination, but it permitted profound early remyelination due to improved phagocytosis of myelin debris by CNS macrophages and prevented disease-associated decline in motor performance...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28347895/metabolomic-changes-in-rat-model-of-cauda-equina-injury
#18
Yang Liu, Rui Yang, Qingjie Kong, Yuan Wang, Bin Zhang, Jingchuan Sun, Yong Yang, Bing Zheng, Hongbin Yuan, Jiangang Shi
BACKGROUND: To show the differences of metabolomic changes in a rat model of cauda equina injury (CEI) and find potent metabolic biomarkers of CEI. METHODS: A total of 28 Sprague-Dawley rats were used in this study. After the rats were given anesthesia and fixed in a prone position, a piece of silicone block was placed into the epidural space below the lamina. Behavior tests including the Basso, Beattie, and Bresnahan open field locomotor scale and an inclined plane test were conducted 1 day and 2 days after surgery...
June 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28287595/bioluminescence-and-near-infrared-imaging-of-optic-neuritis-and-brain-inflammation-in-the-eae-model-of-multiple-sclerosis-in-mice
#19
Katja Schmitz, Irmgard Tegeder
Experimental autoimmune encephalomyelitis (EAE) in SJL/J mice is a model for relapsing-remitting multiple sclerosis (RRMS). Clinical EAE scores describing motor function deficits are basic readouts of the immune-mediated inflammation of the spinal cord. However, scores and body weight do not allow for an in vivo assessment of brain inflammation and optic neuritis. The latter is an early and frequent manifestation in about 2/3 of MS patients. Here, we show methods for bioluminescence and near-infrared live imaging to assess EAE evoked optic neuritis, brain inflammation, and blood-brain barrier (BBB) disruption in living mice using an in vivo imaging system...
March 1, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28286112/the-gut-microbiome-and-microbial-translocation-in-multiple-sclerosis
#20
REVIEW
Ali Mirza, Yang Mao-Draayer
Individuals with multiple sclerosis (MS) have a distinct intestinal microbial community (microbiota) and increased low-grade translocation of bacteria from the intestines into the circulation. The observed change of intestinal bacteria in MS patients regulate immune functions involved in MS pathogenesis. These functions include: systemic and central nervous system (CNS) immunity (including peripheral regulatory T cell function), the blood-brain barrier (BBB) permeability and CNS-resident cell activity. This review discusses the MS intestinal microbiota implication on MS systemic- and CNS-immunopathology...
March 9, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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