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brain endothelium

Yanfang Wang, Jie Liu, Xiaoli Chen, Huimin Sun, Sheng Peng, Yashu Kuang, Jingjiang Pi, Tao Zhuang, Lin Zhang, Zuoren Yu, Brain Tomlinson, Paul Chan, Yihan Chen, Yuzhen Zhang, Ying Li
BACKGROUND: Circulating endothelial-derived microparticles (EMPs) are reported to be increased in acute coronary syndrome (ACS). However, it remains unclear whether EMPs from dysfunctional endothelium participate in the initiation and progression of ACS and what the underlying mechanisms might be. METHODS: Plasma EMPs were measured in 22 patients with ACS and 20 control patients without coronary artery diseases. EMPs from dysfunctional human umbilical vein endothelial cells (HUVECs) stressed by serum-starvation or hypoxia were compared to the EMPs from healthy HUVECs...
October 18, 2018: Journal of Cellular and Molecular Medicine
Leon M T Dicks, Leané Dreyer, Carine Smith, Anton D van Staden
The intestinal barrier, consisting of the vascular endothelium, epithelial cell lining, and mucus layer, covers a surface of about 400 m2 . The integrity of the gut wall is sustained by transcellular proteins forming tight junctions between the epithelial cells. Protected by three layers of mucin, the gut wall forms a non-permeable barrier, keeping digestive enzymes and microorganisms within the luminal space, separate from the blood stream. Microorganisms colonizing the gut may produce bacteriocins in an attempt to outcompete pathogens...
2018: Frontiers in Microbiology
Elisa Cuadrado-Godia, Pratistha Dwivedi, Sanjiv Sharma, Angel Ois Santiago, Jaume Roquer Gonzalez, Mercedes Balcells, John Laird, Monika Turk, Harman S Suri, Andrew Nicolaides, Luca Saba, Narendra N Khanna, Jasjit S Suri
Cerebral small vessel disease (cSVD) has a crucial role in lacunar stroke and brain hemorrhages and is a leading cause of cognitive decline and functional loss in elderly patients. Based on underlying pathophysiology, cSVD can be subdivided into amyloidal and non-amyloidal subtypes. Genetic factors of cSVD play a pivotal role in terms of unraveling molecular mechanism. An important pathophysiological mechanism of cSVD is blood-brain barrier leakage and endothelium dysfunction which gives a clue in identification of the disease through circulating biological markers...
September 2018: Journal of Stroke
Kun-Wei Wu, Ling-Ling Lv, Yu Lei, Cheng Qian, Feng-Yan Sun
Brain microvascular endothelial cells (BMEC) are highly complex regulatory cells that communicate with other cells in the neurovascular unit. Cerebral ischemic injury is known to produce detectable synaptic dysfunction. This study aims to investigate whether endothelial cells in the brain regulate postnatal synaptic development and to elucidate their role in functional recovery after ischemia. Here, we found that in vivo engraftment of endothelial cells increased synaptic puncta and excitatory postsynaptic currents in layers 2/3 of the motor cortex...
October 9, 2018: Neurobiology of Disease
Kristen M Ahlschwede, Geoffry L Curran, Jens T Rosenberg, Samuel C Grant, Gobinda Sarkar, Robert B Jenkins, Subramanian Ramakrishnan, Joseph F Poduslo, Karunya K Kandimalla
Accumulation of amyloid beta (Aβ) peptides in the cerebral vasculature, referred to as cerebral amyloid angiopathy (CAA), is widely observed in Alzheimer's disease (AD) brain and was shown to accelerate cognitive decline. There is no effective method for detecting cerebrovascular amyloid (CVA) and treat CAA. The targeted nanoparticles developed in this study effectively migrated from the blood flow to the vascular endothelium as determined by using quartz crystal microbalance with dissipation monitoring (QCM-D) technology...
October 6, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Shoshy Mizrahy, Anna Gutkin, Paolo Decuzzi, Dan Peer
One of the major challenges in drug development is the delivery of therapeutics to the central nervous system (CNS). The blood-brain barrier (BBB), which modulates the passage of molecules from the CNS, presents a formidable obstacle that limits brain uptake of therapeutics and, therefore, impedes the treatment of multiple neurological pathologies. Targeted nanocarriers present an excellent opportunity for drug delivery into the brain leveraging on endogenous receptors to transport therapeutics across the BBB endothelium...
October 8, 2018: Journal of Drug Targeting
Marcelle Silva-Abreu, Ana Cristina Calpena, Pol Andrés-Benito, Ester Aso, Ignacio A Romero, David Roig-Carles, Radka Gromnicova, Marta Espina, Isidre Ferrer, María Luisa García, David Male
Objective: The first aim of this study was to develop a nanocarrier that could transport the peroxisome proliferator-activated receptor agonist, pioglitazone (PGZ) across brain endothelium and examine the mechanism of nanoparticle transcytosis. The second aim was to determine whether these nanocarriers could successfully treat a mouse model of Alzheimer's disease (AD). Methods: PGZ-loaded nanoparticles (PGZ-NPs) were synthesized by the solvent displacement technique, following a factorial design using poly (lactic-co-glycolic acid) polyethylene glycol (PLGA-PEG)...
2018: International Journal of Nanomedicine
Min Hee Park, Ju Youn Lee, Kang Ho Park, In Kyung Jung, Kyoung-Tae Kim, Yong-Seok Lee, Hyun-Hee Ryu, Yong Jeong, Minseok Kang, Markus Schwaninger, Erich Gulbins, Martin Reichel, Johannes Kornhuber, Tomoyuki Yamaguchi, Hee Jin Kim, Seung Hyun Kim, Edward H Schuchman, Hee Kyung Jin, Jae-Sung Bae
Although many reports have revealed dysfunction of endothelial cells in aging, resulting in blood-brain barrier (BBB) breakdown, the underlying mechanism or mechanisms remain to be explored. Here, we find that acid sphingomyelinase (ASM) is a critical factor for regulating brain endothelial barrier integrity. ASM is increased in brain endothelium and/or plasma of aged humans and aged mice, leading to BBB disruption by increasing caveolae-mediated transcytosis. Genetic inhibition and endothelial-specific knockdown of ASM in mice ameliorated BBB breakdown and neurocognitive impairment during aging...
October 10, 2018: Neuron
Shalinkumar Patel, Alexander L Fedinec, Jianxiong Liu, Max A Weiss, Massroor Pourcyrous, Mimily Harsono, Helena Parfenova, Charles W Leffler
Hydrogen sulfide (H2 S) is an endogenous gasotransmitter that increases cerebral blood flow. In cerebral vascular endothelium, H2 S is produced by cystathionine δ-lyase (CSE). Endothelin-1 (ET-1) has constrictor and dilator influences on cerebral circulation. The mechanism of the vasodilation caused by ET-1 may involve endothelium-derived factors. We hypothesize that ET-1-elicited dilation of pial arterioles requires the elevation of H2 S production in the cerebral vascular endothelium. We investigated the effects of ET-1 on CSE-catalyzed brain H2 S production and pial arteriolar diameter using cranial windows in newborn pigs in vivo...
September 28, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Antje Appelt-Menzel, Alevtina Cubukova, Marco Metzger
Human blood-brain barrier (BBB) in vitro models pose a promising tool in drug development and understanding of mechanistic regulations during health and disease. Human-induced pluripotent stem cells (hiPS cells) represent an unlimited cell source to generate functional cells of the neurovascular unit (NVU), independent of variations or limitations during isolation and in vitro cultivation. This unit describes the standardized 2-D differentiation of adherent hiPS cells into BBB endothelial cells and neuronal stem cells (NSCs)...
September 27, 2018: Current Protocols in Stem Cell Biology
Jing Wang, Meng-Ling Wu, Shou-Pei Cao, Hui Cai, Zhi-Ming Zhao, Yao-Hong Song
Cycloastragenol, a naturally occurring compound in Astragali Radix, has been demonstrated to possess various pharmacological actions including anti-aging, anti-inflammation, anti-fibrosis, antibacterial, liver and endothelium protection. However, whether cycloastragenol ameliorates heart failure remains unclear. Isoproterenol administration to rats triggered classic cardiac damage, as demonstrated by objective parameters of cardiac dysfunction. The treatment of cycloastragenol improved deranged cardiac parameters in the isoproterenol-induced heart damage model in a dose-dependent manner...
November 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Eva Kjer Oernbo, Kasper Lykke, Annette Buur Steffensen, Kathrin Töllner, Christina Kruuse, Martin Fredensborg Rath, Wolfgang Löscher, Nanna MacAulay
BACKGROUND: Cerebral edema can cause life-threatening increase in intracranial pressure. Besides surgical craniectomy performed in severe cases, osmotherapy may be employed to lower the intracranial pressure by osmotic extraction of cerebral fluid upon intravenous infusion of mannitol or NaCl. A so-called rebound effect can, however, hinder continuous reduction in cerebral fluid by yet unresolved mechanisms. METHODS: We determined the brain water and electrolyte content in healthy rats treated with osmotherapy...
September 25, 2018: Fluids and Barriers of the CNS
Rudy Chang, Juan Castillo, Alexander C Zambon, Tatiana B Krasieva, Mark J Fisher, Rachita K Sumbria
Peripheral endothelial cells are capable of erythrophagocytosis, but data on brain endothelial erythrophagocytosis are limited. We studied the relationship between brain endothelial erythrophagocytosis and cerebral microhemorrhage, the pathological substrate of MRI-demonstrable cerebral microbleeds. To demonstrate the erythrophagocytic capability of the brain endothelium, we studied the interactions between brain endothelial cells and red blood cells exposed to oxidative stress in vitro , and developed a new in vitro cerebral microbleeds model to study the subsequent passage of hemoglobin across the brain endothelial monolayer...
2018: Frontiers in Cellular Neuroscience
Nadine Legros, Gottfried Pohlentz, Daniel Steil, Johannes Müthing
Shiga toxin (Stx)-mediated injury of the kidneys and the brain represent the major extraintestinal complications in humans upon infection by enterohemorrhagic Escherichia coli (EHEC). Damage of renal and cerebral endothelial cells is the key event in the pathogenesis of the life-threatening hemolytic uremic syndrome (HUS). Stxs are AB5 toxins and the B-pentamers of the two clinically important Stx subtypes Stx1a and Stx2a preferentially bind to the glycosphingolipid globotriaosylceramide (Gb3Cer, Galα4Galβ4Glcβ1Cer) and to less extent to globotetraosylceramide (Gb4Cer, GalNAcβ3Galα4Galβ4Glcβ1), which are expected to reside in lipid rafts in the plasma membrane of the human endothelium...
September 8, 2018: International Journal of Medical Microbiology: IJMM
Alexandra I Wells, Carolyn B Coyne
Barrier surfaces such as the epithelium lining the respiratory and gastrointestinal (GI) tracts, the endothelium comprising the blood-brain barrier (BBB), and placental trophoblasts provide key physical and immunological protection against viruses. These barriers utilize nonredundant mechanisms to suppress viral infections including the production of interferons (IFNs), which induce a strong antiviral state following receptor binding. However, whereas type I IFNs control infection systemically, type III IFNs (IFN-λs) control infection locally at barrier surfaces and are often preferentially induced by these cells...
October 2018: Trends in Immunology
Nikolay Kutuzov, Henrik Flyvbjerg, Martin Lauritzen
The endothelial cells that form the blood-brain barrier (BBB) are coated with glycocalyx, on the luminal side, and with the basement membrane and astrocyte endfeet, on the abluminal side. However, it is unclear how exactly the glycocalyx and extravascular structures contribute to BBB properties. We used two-photon microscopy in anesthetized mice to record passive transport of four different-sized molecules-sodium fluorescein (376 Da), Alexa Fluor (643 Da), 40-kDa dextran, and 150-kDa dextran-from blood to brain, at the level of single cortical capillaries...
October 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
Helen Q Cai, Vibeke S Catts, Maree J Webster, Cherrie Galletly, Dennis Liu, Maryanne O'Donnell, Thomas W Weickert, Cynthia Shannon Weickert
Elevated pro-inflammatory cytokines exist in both blood and brain of people with schizophrenia but how this affects molecular indices of the blood-brain barrier (BBB) is unclear. Eight mRNAs relating to BBB function, a microglia and three immune cell markers were measured by qPCR in the prefrontal cortex from 37 people with schizophrenia/schizoaffective disorder and 37 matched controls. This cohort was previously grouped into "high inflammation" and "low inflammation" subgroups based on cortical inflammatory-related transcripts...
September 13, 2018: Molecular Psychiatry
Iveta Bernatova, Angelika Puzserova, Peter Balis, Natalia Sestakova, Martina Horvathova, Zuzana Kralovicova, Ingrid Zitnanova
This study was designed to investigate whether oxidative stress, nitric oxide (NO) deficiency and/or endothelial dysfunction (ED) are present in young borderline hypertensive rats (BHR) and whether these pathologies can be causally involved in the initiation of blood pressure (BP) increases. Additionally, we tested the hypothesis that crowding stress, experienced during the peripubertal period, may produce persistent or delayed disorders in corticosterone release, NO synthesis, oxidative status and/or endothelial function that could accelerate BP increases...
2018: Frontiers in Physiology
Rafael Campos, Alberto Fernando Oliveira Justo, Fabíola Z Mónica, José Carlos Cogo, Ronilson Agnaldo Moreno, Valéria Barbosa de Souza, Andre Almeida Schenka, Gilberto De Nucci
Endothelium is the main source of catecholamine release in the electrical-field stimulation (EFS)-induced aortic contractions of the non- venomous snake Panterophis guttatus. However, adrenergic vasomotor control in venomous snakes such as Crotalus durissus terrificus and Bothrops jararaca has not yet been investigated. Crotalus and Bothrops aortic rings were mounted in an organ bath system. EFS-induced aortae contractions were performed in the presence and absence of guanethidine (30 μM), phentolamine (10 μM) or tetrodotoxin (1 μM)...
2018: PloS One
Heba Samaha, Antonella Pignata, Kristen Fousek, Jun Ren, Fong W Lam, Fabio Stossi, Julien Dubrulle, Vita S Salsman, Shanmugarajan Krishnan, Sung-Ha Hong, Matthew L Baker, Ankita Shree, Ahmed Z Gad, Thomas Shum, Dai Fukumura, Tiara T Byrd, Malini Mukherjee, Sean P Marrelli, Jordan S Orange, Sujith K Joseph, Poul H Sorensen, Michael D Taylor, Meenakshi Hegde, Maksim Mamonkin, Rakesh K Jain, Shahenda El-Naggar, Nabil Ahmed
Successful T cell immunotherapy for brain cancer requires that the T cells can access tumour tissues, but this has been difficult to achieve. Here we show that, in contrast to inflammatory brain diseases such as multiple sclerosis, where endothelial cells upregulate ICAM1 and VCAM1 to guide the extravasation of pro-inflammatory cells, cancer endothelium downregulates these molecules to evade immune recognition. By contrast, we found that cancer endothelium upregulates activated leukocyte cell adhesion molecule (ALCAM), which allowed us to overcome this immune-evasion mechanism by creating an ALCAM-restricted homing system (HS)...
September 2018: Nature
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