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https://www.readbyqxmd.com/read/29329699/soluble-cd40-ligand-disrupts-the-blood-brain-barrier-and-exacerbates-inflammation-in-experimental-autoimmune-encephalomyelitis
#1
Hiroki Masuda, Masahiro Mori, Kenta Umehara, Tomomi Furihata, Tomohiko Uchida, Akiyuki Uzawa, Satoshi Kuwabara
Serum soluble CD40 ligand (sCD40L) has been reported to positively correlate with the albumin quotient, a marker of blood-brain barrier (BBB) breakdown, in patients with multiple sclerosis (MS). To clarify the mechanisms of sCD40L in MS pathophysiology, sCD40L was administered to experimental autoimmune encephalomyelitis (EAE) mice and a human brain microvascular endothelial cell (HBMEC)-based BBB model. The high-dose sCD40L group showed a worse EAE score than the low-dose and control groups. BBB permeability was increased by administering sCD40L in a HBMEC-based BBB model...
January 3, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29304411/rapid-screening-of-brain-penetrable-antioxidants-from-natural-products-by-blood-brain-barrier-specific-permeability-assay-combined-with-dpph-recognition
#2
Junfeng Zhu, Xiaojiao Yi, Jinghui Zhang, Shuqing Chen, Yongjiang Wu
Screening brain-penetrable antioxidants from natural products is a promising way for neuroprotective drug discovery. However, there is no screening methodology enables simultaneous investigation of antioxidant activity and blood-brain barrier (BBB) permeability of compounds from complex samples. Here we propose a novel strategy by combining BBB specific parallel artificial membrane permeability assay with 1,1-diphenyl-2-picrylhydrazyl recognition (BBB-PAMPA-DPPH) to achieve rapid multicomponent screening. First, BBB specific artificial membrane was constructed to separate the compounds with high BBB permeability in herbal extracts...
December 28, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29289661/notch-signaling-is-impaired-during-inflammation-in-a-lunatic-fringe-dependent-manner
#3
Claudio Derada Troletti, Melissa A Lopes Pinheiro, Marc Charabati, Elizabeth Gowing, Bert van Het Hof, Susanne M A van der Pol, Dirk Geerts, Alexandre Prat, Ruud D Fontijn, Wendy W Unger, Helga E de Vries
The blood-brain barrier (BBB) assures brain homeostasis through the specialized function of brain endothelial cells (BECs). Dysfunction of the BBB due to inflammatory processes is associated with several neurological disorders, including multiple sclerosis (MS). Understanding the mechanisms that underlie these processes may ultimately lead to new therapeutic strategies to restore BBB function, thereby fighting disease progression. In this study, we demonstrate for the first time a critical role of the Notch signaling pathway in the function of the BBB under resting and inflammatory conditions...
December 28, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29247738/fatty-acid-binding-protein-5-mediates-the-uptake-of-fatty-acids-but-not-drugs-into-human-brain-endothelial-cells
#4
Gordon S Lee, Yijun Pan, Martin J Scanlon, Christopher J H Porter, Joseph A Nicolazzo
The purpose of this study was to examine the involvement of fatty acid binding protein 5 (FABP5), a lipid binding protein expressed at the blood-brain barrier (BBB), in fatty acid and drug uptake into human brain endothelial cells. Following transfection with siRNA against hFABP5, human brain endothelial cell (hCMEC/D3) uptake of lipophilic ligands with varying affinity to FABP5 was assessed with intracellular concentrations quantified by liquid scintillation counting, HPLC or LCMS/MS. The in situ BBB transport of [3H]-diazepam was also assessed in wild type (WT) and FABP5-deficient mice...
December 13, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29232607/simultaneous-uplc-ms-ms-analysis-of-two-stable-isotope-labeled-versions-of-sucrose-in-mouse-plasma-and-brain-samples-as-markers-of-blood-brain-barrier-permeability-and-brain-vascular-space
#5
Ekram Ahmed Chowdhury, Faleh Alqahtani, Raktima Bhattacharya, Reza Mehvar, Ulrich Bickel
Blood Brain Barrier (BBB) permeability is frequently compromised in the course of diseases affecting the central nervous system (CNS). Sucrose is a low molecular weight, hydrophilic marker with slow permeability at the naive BBB and therefore one of the widely used indicators of barrier integrity. Our laboratory recently developed a highly sensitive UPLC-MS/MS method for stable isotope labeled [13C12]sucrose in biological matrices. Correction of total brain concentration for contribution of intravascular space is required in such experiments in order to accurately measure BBB permeability, and it is often accomplished by vascular perfusion with buffer solutions prior to brain sampling...
December 6, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29182998/three-newly-identified-lipophilic-flavonoids-in-tanacetum-parthenium-supercritical-fluid-extract-penetrating-the-blood-brain-barrier
#6
Krisztina Végh, Eszter Riethmüller, Levente Hosszú, András Darcsi, Judit Müller, Ágnes Alberti, Anita Tóth, Szabolcs Béni, Árpád Könczöl, György Tibor Balogh, Ágnes Kéry
Feverfew (Tanacetum parthenium L.) as a perennial herb has been known for centuries due to its medicinal properties. The main sesquiterpene lactone, parthenolide is considered to be responsible for the migraine prophylactic effect, however the pharmacological benefits of the lipophilic flavonoid components can not be neglected. Supercritical fluid extraction (7% ethanol, 22MPa, 64°C) was carried out on the leaves of Tanacetum parthenium L. from which the presence of methylated flavonoids beside parthenolide and other sesquiterpene lactones were indicated by preliminary LC-MS analyses...
November 16, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29173611/a-novel-pacing-strategy-with-low-and-stable-output-pacing-the-left-bundle-branch-immediately-beyond-the-conduction-block
#7
Weijian Huang, Lan Su, Shengjie Wu, Lei Xu, Fangyi Xiao, Xiaohong Zhou, Kenneth A Ellenbogen
This report demonstrates the feasibility of pacing the left bundle branch (LBB) immediately beyond the conduction block to functionally restore the impaired His-Purkinje conduction system in a patient with heart failure and left bundle branch block (LBBB). The pacing required only a low pacing output (0.5 volts/0.5 ms) to correct the LBBB with accompanying right BBB on the electrocardiogram. Over 1-year of follow-up, the patient had a significant improvement in clinical outcome and echocardiographic measurements...
December 2017: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/29158778/helicobacter-pylori-and-gut-microbiota-in-multiple-sclerosis-versus-alzheimer-s-disease-10-pitfalls-of-microbiome-studies
#8
Ah-Mee Park, Seiichi Omura, Mitsugu Fujita, Fumitaka Sato, Ikuo Tsunoda
Alteration of microbiota has been associated with intestinal, inflammatory, and neurological diseases. Abundance of "good bacteria" such as Bifidobacterium, or their products have been generally believed to be beneficial for any diseases, while "bad bacteria" such as pathogenic Helicobacter pylori are assumed to be always detrimental for hosts. However, this is not the case when we compare and contrast the association of the gut microbiota with two neurological diseases, multiple sclerosis (MS) and Alzheimer's disease (AD)...
August 2017: Clinical & Experimental Neuroimmunology
https://www.readbyqxmd.com/read/29151137/blood-brain-barrier-transport-and-neuroprotective-potential-of-blackberry-digested-polyphenols-an-in-vitro-study
#9
Inês Figueira, Lucélia Tavares, Carolina Jardim, Inês Costa, Ana P Terrasso, Andreia F Almeida, Coen Govers, Jurriaan J Mes, Rui Gardner, Jörg D Becker, Gordon J McDougall, Derek Stewart, Augusto Filipe, Kwang S Kim, Dora Brites, Catarina Brito, M Alexandra Brito, Cláudia N Santos
PURPOSE: Epidemiological and intervention studies have attempted to link the health effects of a diet rich in fruits and vegetables with the consumption of polyphenols and their impact in neurodegenerative diseases. Studies have shown that polyphenols can cross the intestinal barrier and reach concentrations in the bloodstream able to exert effects in vivo. However, the effective uptake of polyphenols into the brain is still regarded with some reservations. Here we describe a combination of approaches to examine the putative transport of blackberry-digested polyphenols (BDP) across the blood-brain barrier (BBB) and ultimate evaluation of their neuroprotective effects...
November 18, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/29141800/elevated-plasma-fibrinogen-levels-in-multiple-sclerosis-patients-during-relapse
#10
Jahir Miranda Acuña, Milagros Hidalgo de la Cruz, Alberto Lozano Ros, Saskia Prasca Tapia, Maria Luisa Martínez Ginés, Clara Dionisia de Andrés Frutos
Fibrinogen is a protein that plays a key role in blood coagulation and thrombosis and it is involved in several inflammatory processes; in multiple sclerosis (MS) may be related with blood-brain barrier (BBB) disruption. We analysed the relationship between plasma fibrinogen levels and the presence of active lesions on magnetic resonance imaging (MRI) during relapses of multiple sclerosis (MS) and clinically isolated syndrome (CIS) patients. METHODS: We collected data of patients admitted to a tertiary-care hospital with relapse of MS and CIS from 2008 to 2013 and we analysed the relation between plasma fibrinogen levels (normal: 200mg/dl-417mg/dl) and the presence of active lesions on brain or spinal MRI...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29133510/single-cell-immuno-laser-microdissection-coupled-to-label-free-proteomics-to-reveal-the-proteotypes-of-human-brain-cells-after-ischemia
#11
Teresa García-Berrocoso, Víctor Llombart, Laura Colàs-Campàs, Alexandre Hainard, Virginie Licker, Anna Penalba, Laura Ramiro, Alba Simats, Alejandro Bustamante, Elena Martínez-Saez, Francesc Canals, Jean-Charles Sanchez, Joan Montaner
Cerebral ischemia entails rapid tissue damage in the affected brain area causing devastating neurological dysfunction. How each component of the neurovascular unit contributes or responds to the ischemic insult in the context of the human brain has not been solved yet. Thus, the analysis of the proteome is a straightforward approach to unraveling these cell proteotypes.In this study, post-mortem brain slices from ischemic stroke patients were obtained corresponding to infarcted (IC) and contralateral (CL) areas...
November 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29111495/dual-modal-ultra-bright-nanodots-with-aggregation-induced-emission-and-gadolinium-chelation-for-vascular-integrity-and-leakage-detection
#12
Guangxue Feng, Jackson Liang Yao Li, Carla Claser, Akhila Balachander, Yingrou Tan, Chi Ching Goh, Immanuel Weng Han Kwok, Laurent Rénia, Ben Zhong Tang, Lai Guan Ng, Bin Liu
The study of blood brain barrier (BBB) functions is important for neurological disorder research. However, the lack of suitable tools and methods has hampered the progress of this field. Herein, we present a hybrid nanodot strategy, termed AIE-Gd dots, comprising of a fluorogen with aggregation-induced emission (AIE) characteristics as the core to provide bright and stable fluorescence for optical imaging, and gadolinium (Gd) for accurate quantification of vascular leakage via inductively-coupled plasma mass spectrometry (ICP-MS)...
October 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/29107207/association-of-serum-gamma-glutamyltransferase-and-c-reactive-proteins-with-neuromyelitis-optica-and-multiple-sclerosis
#13
Yaqing Shu, Rui Li, Wei Qiu, Yanyu Chang, Xiaobo Sun, Ling Fang, Chen Chen, Yu Yang, Zhengqi Lu, Xueqiang Hu, Allan G Kermode
BACKGROUND: Many studies have demonstrated that serum gamma glutamyltransferase (GGT) within normal range might be an early marker of oxidative stress. However the role of GGT in neuromyelitis optica (NMO) and multiple sclerosis (MS) is unknown. METHODS: We assessed the correlations among GGT and C-reactive protein (CRP) levels, as well as clinical characteristics of NMO and MS. Serum GGT and CRP levels were measured in 106 NMO patients, 87 MS patients, 79 patients with non-inflammatory neurological diseases (Parkinson disease) and 80 healthy controls (HC)...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29103804/fibrinogen-activates-bmp-signaling-in-oligodendrocyte-progenitor-cells-and-inhibits-remyelination-after-vascular-damage
#14
Mark A Petersen, Jae Kyu Ryu, Kae-Jiun Chang, Ainhoa Etxeberria, Sophia Bardehle, Andrew S Mendiola, Wanjiru Kamau-Devers, Stephen P J Fancy, Andrea Thor, Eric A Bushong, Bernat Baeza-Raja, Catriona A Syme, Michael D Wu, Pamela E Rios Coronado, Anke Meyer-Franke, Stephanie Yahn, Lauriane Pous, Jae K Lee, Christian Schachtrup, Hans Lassmann, Eric J Huang, May H Han, Martina Absinta, Daniel S Reich, Mark H Ellisman, David H Rowitch, Jonah R Chan, Katerina Akassoglou
Blood-brain barrier (BBB) disruption alters the composition of the brain microenvironment by allowing blood proteins into the CNS. However, whether blood-derived molecules serve as extrinsic inhibitors of remyelination is unknown. Here we show that the coagulation factor fibrinogen activates the bone morphogenetic protein (BMP) signaling pathway in oligodendrocyte progenitor cells (OPCs) and suppresses remyelination. Fibrinogen induces phosphorylation of Smad 1/5/8 and inhibits OPC differentiation into myelinating oligodendrocytes (OLs) while promoting an astrocytic fate in vitro...
December 6, 2017: Neuron
https://www.readbyqxmd.com/read/29102509/application-of-an-uhplc-ms-ms-method-to-tissue-distribution-and-excretion-study-of-2-2-hydroxypropanamido-benzoic-acid-in-rats
#15
Qili Zhang, Jiao Guan, Shasha Li, Yunli Zhao, Zhiguo Yu
2-(2-Hydroxypropanamido) benzoic acid (HPABA) is a potential anti-inflammatory agent isolated from the marine fungus Penicillium chrysogenum. In vivo tissue distribution and excretion of HPABA were unknown. Therefore, the purpose of this paper was to establish an UHPLC-MS/MS method for the determination of HPABA and proceed to apply for the study of tissue distribution and excretion in rats. The results obtained indicated that HPABA in tissues was rapidly distributed and cleared. The highest level was found in intestine and stomach, followed by kidney, liver, lung and heart...
October 23, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29079885/therapeutic-potential-of-curcumin-for-multiple-sclerosis
#16
Munibah Qureshi, Ebtesam A Al-Suhaimi, Fazli Wahid, Omer Shehzad, Adeeb Shehzad
Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS), characterized by demyelination, neuronal injury, and breaching of the blood-brain barrier (BBB). Epidemiological studies have shown that immunological, genetic, and environmental factors contribute to the progression and development of MS. T helper 17 (Th17) cells are crucial immunological participant in the pathophysiology of MS. The aberrant production of IL-17 and IL-22 by Th17 cells crosses BBB promotes its disruption and interferes with transmission of nerve signals through activation of neuroinflammation in the CNS...
October 27, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/29032126/weekly-follow-up-of-acute-lesions-in-three-early-multiple-sclerosis-patients-using-mr-spectroscopy-and-diffusion
#17
Gabriel Kocevar, Claudio Stamile, Salem Hannoun, Jean-Amédée Roch, Françoise Durand-Dubief, Sandra Vukusic, François Cotton, Dominique Sappey-Marinier
OBJECT: Pathophysiological mechanisms underlying multiple sclerosis (MS) lesion formation, including inflammation, demyelination/remyelination and axonal damage, and their temporal evolution are still not clearly understood. To this end, three acute white matter lesions were monitored using a weekly multimodal magnetic resonance (MR) protocol. MATERIALS AND METHODS: Three untreated patients with early relapsing-remitting MS and one healthy control subject were followed weekly for two months...
October 13, 2017: Journal of Neuroradiology. Journal de Neuroradiologie
https://www.readbyqxmd.com/read/29031929/permanent-his-bundle-pacing-as-an-alternative-to-biventricular-pacing-for-cardiac-resynchronization-therapy-a-multicenter-experience
#18
Parikshit S Sharma, Gopi Dandamudi, Bengt Herweg, David Wilson, Rajeev Singh, Angela Naperkowski, Jayanthi N Koneru, Kenneth A Ellenbogen, Pugazhendhi Vijayaraman
BACKGROUND: Cardiac resynchronization therapy (CRT) using biventricular pacing (BVP) is effective in patients with heart failure, bundle branch block (BBB), or right ventricular pacing. Permanent His-bundle pacing (HBP) has been reported as an alternative option for CRT. OBJECTIVE: The purpose of this study was to assess the feasibility and outcomes of HBP in CRT eligible or failed patients. METHODS: HBP was attempted as a rescue strategy in patients with failed left ventricular lead or nonresponse to BVP (group I), or as a primary strategy in patients with AV block, BBB, or high ventricular pacing burden as an alternative to BVP (group II) in patients with indications for CRT...
October 12, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29027376/adenosine-a2a-receptor-agonist-ameliorates-eae-and-correlates-with-th1-cytokine-induced-blood-brain-barrier-dysfunction-via-suppression-of-mlck-signaling-pathway
#19
Ying Liu, Marwan Alahiri, Bianca Ulloa, Boxun Xie, Saud A Sadiq
INTRODUCTION: Multiple sclerosis (MS) disease activity is associated with blood-brain barrier (BBB) disruption, which is mediated by inflammatory cytokines released by CD4+ lymphocytes. To assess the effects of adenosine A2A receptors on BBB permeability in vitro and in vivo. METHODS: A2A receptor expression was detected by immunostaining in experimental autoimmune encephalomyelitis (EAE) C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein (MOG)35-55 , and human MS brain...
October 12, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28993949/poly-n-methylated-a%C3%AE-peptide-c-terminal-fragments-meptides-reverse-the-deleterious-effects-of-amyloid-%C3%AE-in-rats
#20
Siya G Sibiya, Musa V Mbandla, Thavi Govender, Adeola Shobo, William M U Daniels
Alzheimer's disease (AD) is characterized by extracellular deposition of amyloid-β (Aβ) plaques. These protein deposits impair synaptic plasticity thereby producing a progressive decline in cognitive function. Current therapies are merely palliative and only slow cognitive decline. Poly-N-methylated Aβ-Peptide C-Terminal Fragments (MEPTIDES) were recently shown to reduce Aβ toxicity in vitro and in Drosophila melanogaster, however whether these novel compounds are effective in inhibiting Aβ-induced toxicity in the mammalian brain remains unclear...
October 9, 2017: Metabolic Brain Disease
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