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Mitchell P McInerney, Irene Volitakis, Ashley I Bush, William A Banks, Jennifer L Short, Joseph A Nicolazzo
PURPOSE: Biometals such as zinc and copper have been shown to affect tight junction expression and subsequently blood-brain barrier (BBB) integrity. Whether these biometals also influence the expression and function of BBB transporters such as P-glycoprotein (P-gp) however is currently unknown. METHODS: Using the immortalised human cerebral microvascular endothelial (hCMEC/D3) cell line, an in-cell western assay (alongside western blotting) assessed relative P-gp expression after treatment with the metal ionophore clioquinol and biometals zinc and copper...
March 5, 2018: Pharmaceutical Research
Zixuan Lin, Yang Li, Pan Su, Deng Mao, Zhiliang Wei, Jay J Pillai, Abhay Moghekar, Matthias van Osch, Yulin Ge, Hanzhang Lu
PURPOSE: Many brain diseases are associated with an alteration in blood-brain barrier (BBB) and its permeability. Current methods using contrast agent are primarily sensitive to major leakage of BBB to macromolecules, but may not detect subtle changes in BBB permeability. The present study aims to develop a novel non-contrast MRI technique for the assessment of BBB permeability to water. METHODS: The central principle is that by measuring arterially labeled blood spins that are drained into cerebral veins, water extraction fraction (E) and permeability-surface-area product (PS) of BBB can be determined...
March 1, 2018: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Catherine Larochelle, Timo Uphaus, Bieke Broux, Elizabeth Gowing, Magdalena Paterka, Laure Michel, Nevenka Dudvarski Stankovic, Frank Bicker, Florent Lemaître, Alexandre Prat, Mirko H H Schmidt, Frauke Zipp
Extracellular matrix (ECM) proteins secreted by blood-brain barrier (BBB) endothelial cells (ECs) are implicated in cell trafficking. We discovered that the expression of ECM epidermal growth factor-like protein 7 (EGFL7) is increased in the CNS vasculature of patients with multiple sclerosis (MS), and in mice with experimental autoimmune encephalomyelitis (EAE). Perivascular CD4 T lymphocytes colocalize with ECM-bound EGFL7 in MS lesions. Human and mouse activated T cells upregulate EGFL7 ligand αvβ3 integrin and can adhere to EGFL7 through integrin αvβ3...
February 26, 2018: Nature Communications
Jennifer M Rutkowsky, Linda L Lee, Michelle Puchowicz, Mari S Golub, Douglas E Befroy, Dennis W Wilson, Steven Anderson, Gary Cline, Jason Bini, Kamil Borkowski, Trina A Knotts, John C Rutledge
Recent work suggests that diet affects brain metabolism thereby impacting cognitive function. Our objective was to determine if a western diet altered brain metabolism, increased blood-brain barrier (BBB) transport and inflammation, and induced cognitive impairment in C57BL/6 (WT) mice and low-density lipoprotein receptor null (LDLr -/-) mice, a model of hyperlipidemia and cognitive decline. We show that a western diet and LDLr -/- moderately influence cognitive processes as assessed by Y-maze and radial arm water maze...
2018: PloS One
Giacomo Russo, Lucia Grumetto, Roman Szucs, Francesco Barbato, Frederic Lynen
The Blood-Brain Barrier (BBB) plays an essential role in protecting the brain tissues against possible injurious substances. In the present work, 79 neutral, basic, acidic and amphoteric structurally unrelated analytes were considered and their chromatographic retention coefficients on immobilized artificial membrane (IAM) stationary phase were determined employing a mass spectrometry (MS) -compatible buffer based on ammonium acetate. Their BBB passage predictive strength was evaluated and the statistical models based on IAM indexes and in silico physico-chemical descriptors showed solid statistics (r2 (n-1) = 0...
February 7, 2018: European Journal of Pharmaceutics and Biopharmaceutics
Raya Eilam, Menahem Segal, Rafael Malach, Michael Sela, Ruth Arnon, Rina Aharoni
To elucidate mechanisms contributing to cortical pathology in multiple sclerosis (MS), we investigated neurovascular aberrations, in particular the association of astrocytes with cortical neurons and blood vessels, in mice induced with experimental autoimmune encephalomyelitis (EAE). Blood-brain barrier (BBB) dysfunction was evident by leakage of the tracer sodium fluorescein, along with reduced expression of claudin-5 by endothelial cells and desmin by pericytes. Immunohistological and ultrastructural analyses revealed detachment of the astroglial cell bodies from the blood vessels and loss of their connections with both the blood vessels and the neuronal synapses...
February 9, 2018: Glia
Pu Guo, Aimei Liu, Deyu Huang, Qinghua Wu, Zainab Fatima, Yanfei Tao, Guyue Cheng, Xu Wang, Zonghui Yuan
T-2 toxin, a trichothecene mycotoxin, is a common contaminant in food and animal feed, and is also present in processed cereal products. The most common route of T-2 toxin exposure in humans is through dietary ingestion. The cytotoxic effects of T-2 toxin include modifications to feeding behavior, nervous disorders, cardiovascular alterations, immunosuppression, and hemostatic derangements. However, to date, effects on the central nervous system (CNS) have rarely been reported. In the present study, female Wistar rat were given a single dose of T-2 toxin at 2 mg/kg b...
January 27, 2018: Toxicology Letters
Lior Yankelson, Aviram Hochstadt, Ben Sadeh, Benley Pick, Ariel Finkelstein, Raphael Rosso, Sami Viskin
OBJECTIVES: To predict the QT interval in the presence of normal QRS for patients with left bundle branch block (LBBB). BACKGROUND: There is no acceptable method for simple and reliable QT correction for patients with bundle branch block (BBB). METHODS: We measured the QT interval in patients with new onset LBBB who had a recent electrocardiogram with narrow QRS for comparison. 48 patients who developed in-hospital LBBB were studied. Patients who had similar heart rate before and after LBBB were included...
January 30, 2018: Journal of Electrocardiology
Nicholas Dopkins, Prakash S Nagarkatti, Mitzi Nagarkatti
The importance of the gut microbiome in the regulation of non-infectious diseases has earned recently an unprecedented interest from biomedical researchers. Widespread use of next generation sequencing techniques have prepared a foundation for further research by correlating the presence of specific bacterial species with an onset or severity of a disease state, heralded paradigm-shifting results. This review covers the mechanisms through which a dysbiotic gut microbiota contributes to the pathological symptoms in an autoimmune neurodegenerative disorder, Multiple Sclerosis (MS)...
February 2, 2018: Immunology
Zhiyang Lv, Yuwei Yang, Jie Wang, Jing Chen, Junsong Li, Liuqing Di
Ginkgolides (GG), containing ginkgolide A (GA), ginkgolide B (GB) and ginkgolide C (GC), are mainly prescribed for ischemic stroke and cerebral infarction. However, the ginkgolides can hardly pass the blood-brain barrier (BBB) into the brain. The purpose of this study was to prepare borneol-modified ginkgolides liposomes (GGB-LPs) to study whether borneol could enhance the transport of ginkgolides across the BBB. The preparation conditions of GGB-LPs were optimized by a response surface-central composite design...
January 31, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Hermes As Kamimura, Julien Flament, Julien Valette, Andrea Cafarelli, Romina Aron Badin, Philippe Hantraye, Benoît Larrat
Focused ultrasound (FUS) in combination with microbubbles is capable of noninvasive, site-targeted delivery of drugs through the blood-brain barrier (BBB). Although acoustic parameters are reproducible in small animals, their control remains challenging in primates due to skull heterogeneity. This study describes a 7-T magnetic resonance (MR)-guided FUS system designed for BBB disruption in non-human primates (NHP) with a robust feedback control based on passive cavitation detection (PCD). Contrast enhanced T1-weighted MR images confirmed the BBB opening in NHP sonicated during 2 min with 500-kHz frequency, pulse length of 10 ms, and pulse repetition frequency of 5 Hz...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
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
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
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
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
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
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...
February 5, 2018: Journal of Pharmaceutical and Biomedical Analysis
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
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
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
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