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https://www.readbyqxmd.com/read/29753957/brainstem-blood-brain-barrier-disruption-using-focused-ultrasound-a-demonstration-of-feasibility-and-enhanced-doxorubicin-delivery
#1
Saira Alli, Carlyn A Figueiredo, Brian Golbourn, Nesrin Sabha, Megan Yijun Wu, Andrew Bondoc, Amanda Luck, Daniel Coluccia, Colin Maslink, Christian Smith, Heiko Wurdak, Kullervo Hynynen, Meaghan O'Reilly, James T Rutka
Magnetic Resonance Image-guided Focused Ultrasound (MRgFUS) has been used to achieve transient BBB opening without tissue injury. Delivery of a targeted ultrasonic wave causes an interaction between administered microbubbles and the capillary bed resulting in enhanced vessel permeability. The use of MRgFUS in the brainstem has not previously been shown but could provide value in the treatment of tumours such as Diffuse Intrinsic Pontine Glioma (DIPG) where the intact BBB has contributed to the limited success of chemotherapy...
May 10, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29692758/food-derived-hemorphins-cross-intestinal-and-blood-brain-barriers-in-vitro
#2
Dorothée Domenger, Benoit Cudennec, Mostafa Kouach, Véronique Touche, Christophe Landry, Jean Lesage, Fabien Gosselet, Sophie Lestavel, Jean-François Goossens, Pascal Dhulster, Rozenn Ravallec
A qualitative study is presented, where the main question was whether food-derived hemorphins, i.e., originating from digested alimentary hemoglobin, could pass the intestinal barrier and/or the blood-brain barrier (BBB). Once absorbed, hemorphins are opioid receptor (OR) ligands that may interact with peripheral and central OR and have effects on food intake and energy balance regulation. LLVV-YPWT (LLVV-H4), LVV-H4, VV-H4, VV-YPWTQRF (VV-H7), and VV-H7 hemorphins that were previously identified in the 120 min digest resulting from the simulated gastrointestinal digestion of hemoglobin have been synthesized to be tested in in vitro models of passage of IB and BBB...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29671324/discovery-of-lipidome-alterations-following-traumatic-brain-injury-via-high-resolution-metabolomics
#3
Scott R Hogan, John H Phan, Melissa Alvarado-Velez, May Dongmei Wang, Ravi V Bellamkonda, Facundo M Fernandez, Michelle C LaPlaca
Traumatic brain injury (TBI) can occur across wide segments of the population, presenting in a heterogeneous manner that makes diagnosis inconsistent and management challenging. Biomarkers offer the potential to objectively identify injury status, severity, and phenotype by measuring the relative concentrations of endogenous molecules in readily accessible biofluids. Through a data-driven, discovery approach, novel biomarker candidates for TBI were identified in the serum lipidome of adult male Sprague-Dawley rats in the first week following moderate controlled cortical impact (CCI)...
April 19, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29653366/bufalin-inhibits-glioblastoma-growth-by-promoting-proteasomal-degradation-of-the-na-k-atpase-%C3%AE-1-subunit
#4
Yu-Long Lan, Xun Wang, Jia-Cheng Lou, Jin-Shan Xing, Zhen-Long Yu, Hongjin Wang, Shuang Zou, Xiaochi Ma, Bo Zhang
Chansu is a traditional Chinese medicine that is generally recognized as a specific inhibitor of Na+ /K+ -ATPase. Bufalin, an active component of Chansu, is an endogenous steroid hormone with great potential as a cancer treatment. However, the mechanism by which it exerts its antitumor activity requires further research. Currently, the α1 subunit of Na+ /K+ -ATPase (ATP1A1) is known to exert important roles in tumorigenesis, and the precise mechanisms underlying the effect of Bufalin on the Na+ /K+ -ATPase α1 subunit was therefore investigated in this study to determine its role in glioblastoma treatments...
April 10, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29619025/mast-cells-and-innate-lymphoid-cells-underappreciated-players-in-cns-autoimmune-demyelinating-disease
#5
REVIEW
Melissa A Brown, Rebecca B Weinberg
Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis, are autoimmune CNS inflammatory diseases. As a result of a breakdown in the relatively impermeable blood-brain barrier (BBB) in affected individuals, myelin-specific CD4+ and CD8+ T cells gain entry into the immune privileged CNS and initiate myelin, oligodendrocyte, and nerve axon destruction. However, despite the absolute requirement for T cells, there is increasing evidence that innate immune cells also play critical amplifying roles in disease pathogenesis...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29576053/qualitative-detection-of-ginsenosides-in-brain-tissues-after-oral-administration-of-high-purity-ginseng-total-saponins-by-using-polyclonal-antibody-against-ginsenosides
#6
Yu-Nan Zhao, Xiao Shao, Liu-Feng Ouyang, Lin Chen, Ling Gu
Given the limited studies and conflicting findings, the transport character of ginsenosides crossing the blood-brain barrier (BBB) remains unclear. The present study was designed to qualitatively determine the distribution of ginsenosides in brain tissues after oral administration of ginseng total saponins, using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with immunohistochemistry. In brain tissue homogenates, ginsenoside Rg1 was detectable and no other ginsenosides or their metabolites were found...
March 2018: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/29574788/mechanisms-underlying-lesion-development-and-lesion-distribution-in-cns-autoimmunity
#7
REVIEW
Maren Lindner, Luisa Klotz, Heinz Wiendl
It is widely accepted that development of autoimmunity in the central nervous system (CNS) is triggered by autoreactive T cells, that are activated in the periphery and gain the capacity to migrate through endothelial cells at the blood-brain-barrier (BBB) into the CNS. Upon local reactivation, an inflammatory cascade is initiated, that subsequently leads to a recruitment of additional immune cells ultimately causing demyelination and axonal damage. Even though the interaction of immune cells with the BBB has been in the focus of research for many years, the exact mechanisms of how immune cells enter and exit the CNS remains poorly understood...
March 25, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29571849/oligoclonal-bands-and-periventricular-lesions-in-multiple-sclerosis-will-not-increase-blood-brain-barrier-permeability
#8
Tetsuya Akaishi, Toshiyuki Takahashi, Ichiro Nakashima
OBJECTIVE: To elucidate the etiology and clinical significance of periventricular lesions (PVLs) and oligoclonal bands (OB) in multiple sclerosis (MS). METHODS: We enrolled a total of 97 MS patients (67 OB-positive and 30 OB-negative) who were negative both for anti-aquaporin-4 (AQP4) autoantibody and anti-myelin oligodendrocyte glycoprotein (MOG) antibody. In these patients, comprehensive data including clinical, laboratory, and MRI were collected to investigate the significance of OB and PVLs...
April 15, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29508078/ionophore-and-biometal-modulation-of-p-glycoprotein-expression-and-function-in-human-brain-microvascular-endothelial-cells
#9
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
https://www.readbyqxmd.com/read/29498097/non-contrast-mr-imaging-of-blood-brain-barrier-permeability-to-water
#10
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
https://www.readbyqxmd.com/read/29483510/egfl7-reduces-cns-inflammation-in-mouse
#11
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
https://www.readbyqxmd.com/read/29444171/reduced-cognitive-function-increased-blood-brain-barrier-transport-and-inflammatory-responses-and-altered-brain-metabolites-in-ldlr-and-c57bl-6-mice-fed-a-western-diet
#12
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
https://www.readbyqxmd.com/read/29427629/screening-therapeutics-according-to-their-uptake-across-the-blood-brain-barrier-a-high-throughput-method-based-on-immobilized-artificial-membrane-liquid-chromatography-diode-array-detection-coupled-to-electrospray-time-of-flight-mass-spectrometry
#13
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
https://www.readbyqxmd.com/read/29424049/astrocyte-disruption-of-neurovascular-communication-is-linked-to-cortical-damage-in-an-animal-model-of-multiple-sclerosis
#14
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...
May 2018: Glia
https://www.readbyqxmd.com/read/29413859/brain-damage-and-neurological-symptoms-induced-by-t-2-toxin-in-rat-brain
#15
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...
April 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29395105/new-formula-for-defining-normal-and-prolonged-qt-in-patients-with-bundle-branch-block
#16
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
https://www.readbyqxmd.com/read/29392733/the-role-of-gut-microbiome-and-associated-metabolome-in-the-regulation-of-neuroinflammation-in-multiple-sclerosis-and-its-implications-in-attenuating-chronic-inflammation-in-other-inflammatory-and-autoimmune-disorders
#17
REVIEW
Nicholas Dopkins, Prakash S Nagarkatti, Mitzi Nagarkatti
The importance of the gut microbiome in the regulation of non-infectious diseases has earned unprecedented interest from biomedical researchers. Widespread use of next-generation sequencing techniques has prepared a foundation for further research by correlating the presence of specific bacterial species with the onset or severity of a disease state, heralding 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
https://www.readbyqxmd.com/read/29385087/optimization-of-the-preparation-conditions-of-borneol-modified-ginkgolide-liposomes-by-response-surface-methodology-and-study-of-their-blood-brain-barrier-permeability
#18
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
https://www.readbyqxmd.com/read/29381130/feedback-control-of-microbubble-cavitation-for-ultrasound-mediated-blood-brain-barrier-disruption-in-non-human-primates-under-magnetic-resonance-guidance
#19
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
https://www.readbyqxmd.com/read/29329699/soluble-cd40-ligand-disrupts-the-blood-brain-barrier-and-exacerbates-inflammation-in-experimental-autoimmune-encephalomyelitis
#20
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...
March 15, 2018: Journal of Neuroimmunology
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