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brain endothelium

Shannon L Faley, Emma H Neal, Jason X Wang, Allison M Bosworth, Callie M Weber, Kylie M Balotin, Ethan S Lippmann, Leon M Bellan
There is a profound need for functional, biomimetic in vitro tissue constructs of the human blood-brain barrier and neurovascular unit (NVU) to model diseases and identify therapeutic interventions. Here, we show that induced pluripotent stem cell (iPSC)-derived human brain microvascular endothelial cells (BMECs) exhibit robust barrier functionality when cultured in 3D channels within gelatin hydrogels. We determined that BMECs cultured in 3D under perfusion conditions were 10-100 times less permeable to sodium fluorescein, 3 kDa dextran, and albumin relative to human umbilical vein endothelial cell and human dermal microvascular endothelial cell controls, and the BMECs maintained barrier function for up to 21 days...
January 31, 2019: Stem Cell Reports
Arnon Blum, Nina Pastukh, Rizak Sirchan, Nava Blum, Lev Chernikoff, Vladimir Vaispapir
BACKGROUND: Endothelial progenitor cells may have a role in ongoing endothelial repair. Impaired mobilization or depletion of these cells may contribute to progression of vascular disease. Our hypothesis was that endothelial progenitor cells would be suppressed in patients with acute cerebrovascular event based on our previous study that found severe endothelial dysfunction in those patients. OBJECTIVES: To study the ability of patients with acute stroke to build colonies of endothelial progenitor cells...
February 2019: Israel Medical Association Journal: IMAJ
Hyo Min Cho, Hee Kyung Jin, Jae-Sung Bae
Although many studies have reported that the breakdown of the blood-brain barrier (BBB) represents one of the major pathological changes in aging, the mechanism underlying this process remains relatively unexplored. In this study, we described that acid sphingomyelinase (ASM) derived from endothelial cells plays a critical role in BBB disruption in aging. ASM levels were elevated in the brain endothelium and plasma of aged humans and mice, resulting in BBB leakage through an increase in caveolae-mediated transcytosis...
February 14, 2019: BMB Reports
Md A Hakim, Erik J Behringer
Cerebral arteries and their respective microcirculation deliver oxygen and nutrients to the brain via blood flow regulation. Endothelial cells line the lumen of blood vessels and command changes in vascular diameter as needed to meet the metabolic demand of neurons. Primary endothelial-dependent signaling pathways of hyperpolarization of membrane potential (Vm) and nitric oxide typically operate in parallel to mediate vasodilation and thereby increase blood flow. Although integral to coordinating vasodilation over several millimeters of vascular length, components of endothelium-derived hyperpolarization (EDH) have been historically difficult to measure...
January 20, 2019: Journal of Visualized Experiments: JoVE
Yoshiki Hase, Ren Ding, Gina Harrison, Emily Hawthorne, Amilia King, Sean Gettings, Charlotte Platten, William Stevenson, Lucinda J L Craggs, Raj N Kalaria
Previous studies suggest white matter (WM) integrity is vulnerable to chronic hypoperfusion during brain ageing. We assessed ~ 0.7 million capillary profiles in the frontal lobe WM across several dementias comprising Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease with dementia, vascular dementia, mixed dementias, post-stroke dementia as well as post-stroke no dementia and similar age ageing and young controls without significant brain pathology. Standard histopathological methods were used to determine microvascular pathology and capillary width and densities in 153 subjects using markers of the basement membrane (collagen IV; COL4) and endothelium (glucose transporter-1; GLUT-1)...
February 7, 2019: Acta Neuropathologica Communications
Richard F Keep, Hazel C Jones, Lester R Drewes
This editorial focuses on the progress made in brain barrier and brain fluid research in 2018. It highlights some recent advances in knowledge and techniques, as well as prevalent themes and controversies. Areas covered include: modeling, the brain endothelium, the neurovascular unit, the blood-CSF barrier and CSF, drug delivery, fluid movement within the brain, the impact of disease states, and heterogeneity.
February 5, 2019: Fluids and Barriers of the CNS
Hildegard Herman, Csilla Fazakas, János Haskó, Kinga Molnár, Ádám Mészáros, Ádám Nyúl-Tóth, Gábor Szabó, Ferenc Erdélyi, Aurel Ardelean, Anca Hermenean, István A Krizbai, Imola Wilhelm
Breast cancer and melanoma are among the most frequent cancer types leading to brain metastases. Despite the unquestionable clinical significance, important aspects of the development of secondary tumours of the central nervous system are largely uncharacterized, including extravasation of metastatic cells through the blood-brain barrier. By using transmission electron microscopy, here we followed interactions of cancer cells and brain endothelial cells during the adhesion, intercalation/incorporation and transendothelial migration steps...
February 2, 2019: Journal of Cellular and Molecular Medicine
Pankaj Bhatia, Nirmal Singh
Cerebral hypoperfusion has been associated with increased risk of vascular dementia (VaD). The present study investigates the potential of Tadalafil, a phosphodiesterase-5 inhibitor, in rat model of bilateral common carotid artery occlusion (BCCAo) induced VaD. Wistar rats were subjected to BCCAo procedure under anesthesia to induce VaD. Morris water-maze (MWM) test (7thday onwards post-surgery) was employed to assess learning and memory whereby escape latency time, time spent in target quadrant, Path length and average swim speed taken as important parameters...
January 30, 2019: Current Neurovascular Research
Sha Tan, Yilong Shan, Yinyao Lin, Siyuan Liao, Bingjun Zhang, Qin Zeng, Yuge Wang, Zhezhi Deng, Chen Chen, Xueqiang Hu, Lisheng Peng, Wei Qiu, Zhengqi Lu
Astrocytes mediate the destruction of the blood-brain barrier (BBB) during ischemic stroke (IS). IL-9 is a pleiotropic cytokine that we previously found to be highly expressed in peripheral blood mononuclear cells from patients with IS, and the presence of IL-9 receptors on astrocytes has been reported in the literature. Here, we detected the effect of IL-9 on astrocytes using an anti-IL-9-neutralizing antibody to treat rats with experimental stroke. Supernatants from astrocytes treated with or without oxygen-glucose deprivation and/or IL-9 were incubated with bEnd...
January 29, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Jyoti Gautam, Jeffrey H Miner, Yao Yao
Endothelial cells make laminin-411 and laminin-511. Although laminin-411 is well studied, the role of laminin-511 remains largely unknown due to the embryonic lethality of lama5-/- mutants. In this study, we generated endothelium-specific lama5 conditional knockout (α5-TKO) mice and investigated the biological functions of endothelial lama5 in blood-brain barrier (BBB) maintenance under homeostatic conditions and the pathogenesis of intracerebral hemorrhage (ICH). First, the BBB integrity of α5-TKO mice was measured under homeostatic conditions...
January 29, 2019: Translational Stroke Research
Xin-Kang Tong, Lianne J Trigiani, Edith Hamel
Transgenic mice overexpressing transforming growth factor-β1 (TGF mice) display impaired cerebrovascular reactivity, cerebral hypoperfusion and neurovascular uncoupling, but no overt cognitive deficits until old age. Cardiovascular diseases are a major risk factor for vascular cognitive impairment and dementia (VCID). We investigated the impact of a high cholesterol diet (HCD) on cerebrovascular and cognitive function in adult (6 months) and aged (12 months) TGF mice, together with the potential benefit of simvastatin (SV), an anti-cholesterol drug with pleiotropic effects, in adult mice...
January 28, 2019: Cell Death & Disease
Luc Bertrand, Hyung Joon Cho, Michal Toborek
Pericytes are multifunctional cells wrapped around endothelial cells via cytoplasmic processes that extend along the abluminal surface of the endothelium. The interactions between endothelial cells and pericytes of the blood-brain barrier are necessary for proper formation, development, stabilization, and maintenance of the blood-brain barrier. Blood-brain barrier pericytes regulate paracellular flow between cells, transendothelial fluid transport, maintain optimal chemical composition of the surrounding microenvironment, and protect endothelial cells from potential harmful substances...
January 21, 2019: Brain: a Journal of Neurology
Iwona Pelikant-Małecka, Ryszard T Smoleński, Ewa M Słomińska
4-pyridone-3-carboxamide-1β-D-ribonucleoside (4PYR) is a derivative of nicotinamide found physiologically in human body fluids that can be metabolized to mono-, di- or triphosphate derivatives (4PYMP, 4PYDP and 4PYTP respectively) and an analogue of NAD - the 1-β-D-ribonucleoside-4-pyridone-3-carboxamide adenine dinucleotide (4PYRAD) in human cells. The European Uremic Toxin Work Group (EUTox) has classified 4PYR as a uremic toxin that adversely affects endothelium. This study aimed to investigate the metabolism of 4PYR in murine brain microvascular endothelial cells (mBMECs)...
January 19, 2019: Nucleosides, Nucleotides & Nucleic Acids
Mariana Castro Dias, Caroline Coisne, Ivana Lazarevic, Pascale Baden, Masaki Hata, Noriko Iwamoto, David Miguel Ferreira Francisco, Michael Vanlandewijck, Liqun He, Felix A Baier, Deborah Stroka, Rémy Bruggmann, Ruth Lyck, Gaby Enzmann, Urban Deutsch, Christer Betsholtz, Mikio Furuse, Shoichiro Tsukita, Britta Engelhardt
The tight junction protein claudin-3 has been identified as a transcriptional target of the Wnt/β-catenin signaling pathway regulating blood-brain barrier (BBB) maturation. In neurological disorders loss of claudin-3 immunostaining is observed at the compromised BBB and blood-cerebrospinal fluid barrier (BCSFB). Although these observations support a central role of claudin-3 in regulating brain barriers' tight junction integrity, expression of claudin-3 at the brain barriers has remained a matter of debate...
January 18, 2019: Scientific Reports
Ange Landela Luzolo, Dieudonné Mumba Ngoyi
Malaria remains of significant public health concern under the tropics, causing millions of deaths annually. The disease is caused by protozoans of the Plasmodium genus, of which harbors several distinct species. Human infection occurs during the blood meal of an infected female mosquito belonging to the Anopheles genus. It is estimated that around 1 % of children infected with Plasmodium falciparum develops a more severe form of malaria, which may eventually lead to cerebral complications including cerebral malaria (CM)...
January 15, 2019: Brain Research Bulletin
Cathrin J Czupalla, Hanadie Yousef, Tony Wyss-Coray, Eugene C Butcher
The brain endothelium is a highly specialized vascular structure that maintains the activity and integrity of the central nervous system (CNS). Previous studies have reported that the integrity of the brain endothelium is compromised in a plethora of neuropathologies. Therefore, it is of particular interest to establish a method that enables researchers to investigate and understand the molecular changes in CNS endothelial cells and underlying mechanisms in conjunction with murine models of disease. In the past, approaches to isolate endothelial cells have either involved the use of transgenic reporter mice or suffered from insufficiently pure cell populations and poor yield...
November 20, 2018: Bio-protocol
Agadha C Wickremesekera, Helen D Brasch, Valerie M Lee, Paul F Davis, Kelvin Woon, Reuben Johnson, Swee T Tan, Tinte Itinteang
We have recently characterized cancer stem cell (CSC) subpopulations in different types of cancer. This study aimed to identify and characterize CSCs within metastatic melanoma (MM) to the brain. 3, 3-diaminobenzidine (DAB) immunohistochemical (IHC) staining of ten samples of MM to the brain demonstrated the expression of the embryonic stem cell (ESC) markers OCT4, NANOG, SALL4, SOX2 and pSTAT3. Protein expression of all five ESC markers except SALL4 were confirmed by Western blotting on five samples and transcriptional activation of all five markers was demonstrated using NanoString mRNA analysis on four samples...
February 2019: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Rajinikanth Gogiraju, Astrid Hubert, Jörg Fahrer, Beate K Straub, Moritz Brandt, Philip Wenzel, Thomas Münzel, Stavros Konstantinides, Gerd Hasenfuss, Katrin Schäfer
BACKGROUND: Cardiac remodeling is modulated by overnutrition or starvation. The adipokine leptin mediates energy balance between adipose tissue and brain. Leptin and its receptors are expressed in the heart. METHODS AND RESULTS: To examine the importance of endothelial leptin signaling in cardiac hypertrophy, transverse aortic constriction was used in mice with inducible endothelium-specific deletion of leptin receptors (End.LepR-KO) or littermate controls (End...
January 2019: Circulation. Heart Failure
Angelika Hoffmann, Johannes Pfeil, Ann-Kristin Mueller, Jessica Jin, Katrin Deumelandt, Xavier Helluy, Cuihua Wang, Sabine Heiland, Michael Platten, John W Chen, Martin Bendszus, Michael O Breckwoldt
Purpose To investigate the association of inflammation and brain edema in a cerebral malaria (CM) mouse model with a combination of bis-5-hydroxy-tryptamide-diethylenetriaminepentaacetate gadolinium, referred to as MPO-Gd, and cross-linked iron oxide nanoparticle (CLIO-NP) imaging. Materials and Methods Female wild-type (n = 23) and myeloperoxidase (MPO) knock-out (n = 5) mice were infected with the Plasmodium berghei ANKA strain from May 2016 to July 2018. Seven healthy mice served as control animals. At a Rapid Murine Coma and Behavioral Scale (RMCBS) score of less than 15, mice underwent MRI at 9...
December 4, 2018: Radiology
Mathias Kaiser, Malgorzata Burek, Stefan Britz, Frauke Lankamp, Steffi Ketelhut, Björn Kemper, Carola Förster, Christian Gorzelanny, Francisco M Goycoolea
Microvascular endothelial cells are an essential part of many biological barriers, such as the blood⁻brain barrier (BBB) and the endothelium of the arteries and veins. A reversible opening strategy to increase the permeability of drugs across the BBB could lead to improved therapies due to enhanced drug bioavailability. Vanilloids, such as capsaicin, are known to reversibly open tight junctions of epithelial and endothelial cells. In this study, we used several in vitro assays with the murine endothelial capillary brain cells (line cEND) as a BBB model to characterize the interaction between capsaicin and endothelial tight junctions...
December 30, 2018: International Journal of Molecular Sciences
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