TY - JOUR AU - Walter, Fruzsina AU - Harazin, András AU - Tóth, Andrea AU - Veszelka, Szilvia AU - Santa Maria, Anaraquel AU - Barna, Lilla AU - Kincses, András AU - Biczo, G AU - Balla, Zsolt AU - Kui, Balázs AU - Maléth, József AU - Cervenak, László AU - Tubak, Vilmos AU - Kittel, Ágnes AU - Rakonczay, Zoltán AU - Deli, Mária Anna TI - Blood–brain barrier dysfunction in l-ornithine induced acute pancreatitis in rats and the direct effect of l-ornithine on cultured brain endothelial cells JF - FLUIDS AND BARRIERS OF THE CNS J2 - FLUIDS BARRIERS CNS VL - 19 PY - 2022 IS - 1 PG - 20 SN - 2045-8118 DO - 10.1186/s12987-022-00308-0 UR - https://m2.mtmt.hu/api/publication/32667372 ID - 32667372 N1 - Institute of Biophysics, Biological Research Centre, Temesvári krt. 62, Szeged, 6726, Hungary Department of Medicine, University of Szeged, Kálvária sgt 57, Szeged, 6725, Hungary Department of Pathophysiology, University of Szeged, Semmelweis u. 1, Szeged, 6701, Hungary HAS-USZ Momentum Epithelial Cell Signaling and Secretion Research Group, University of Szeged, Dóm sqr. 10, Szeged, 6720, Hungary HCEMM-SZTE Molecular Gastroenterology Research Group, University of Szeged, Dóm sqr. 10, Szeged, 6720, Hungary Department of Internal Medicine and Hematology, Research Laboratory, Semmelweis University, Üllői út 26, Budapest, 1085, Hungary Creative Laboratory Ltd, Temesvári krt. 62, Szeged, 6726, Hungary Institute of Experimental Medicine, Eötvös Loránd Research Network, Szigony u. 43, Budapest, 1083, Hungary Wyss Institute for Biologically Inspired Engineering at Harvard University, 3 Blackfan Circle, Boston, MA 02115, United States Department of Biomedicine, Faculty of Health, Aarhus University, Høegh-Guldbergs Gade 10, Aarhus C, 8000, Denmark Institute of Applied Sciences, Department of Environmental Biology and Education, Juhász Gyula Faculty of Education, University of Szeged, Boldogasszony sgt. 6, Szeged, 6725, Hungary Cited By :1 Export Date: 23 November 2022 Correspondence Address: Deli, M.A.; Institute of Biophysics, Temesvári krt. 62, Hungary; email: deli.maria@brc.hu LA - English DB - MTMT ER - TY - JOUR AU - Watanabe, Daisuke AU - Nakagawa, Shinsuke AU - Morofuji, Yoichi AU - Tóth, Andrea AU - Vastag, Monika AU - Aruga, Jun AU - Niwa, Masami AU - Deli, Mária Anna TI - Characterization of a Primate Blood-Brain Barrier Co-Culture Model Prepared from Primary Brain Endothelial Cells, Pericytes and Astrocytes JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 13 PY - 2021 IS - 9 SN - 1999-4923 DO - 10.3390/pharmaceutics13091484 UR - https://m2.mtmt.hu/api/publication/32242365 ID - 32242365 N1 - Cited By :3 Export Date: 13 September 2022 LA - English DB - MTMT ER - TY - JOUR AU - Veszelka, Szilvia AU - Tóth, András AU - Walter, Fruzsina AU - Tóth, Andrea AU - Gróf, Ilona AU - Mészáros, Mária AU - Bocsik, Alexandra AU - Virághné Hellinger, Éva AU - Vastag, M AU - Rákhely, Gábor AU - Deli, Mária Anna TI - Comparison of a rat primary cell-based blood-brain barrier model with epithelial and brain endothelial cell lines: gene expression and drug transport JF - FRONTIERS IN MOLECULAR NEUROSCIENCE J2 - FRONT MOL NEUROSCI VL - 11 ET - 0 PY - 2018 PG - 20 SN - 1662-5099 DO - 10.3389/fnmol.2018.00166 UR - https://m2.mtmt.hu/api/publication/3365532 ID - 3365532 N1 - These authors have contributed equally to this work: Szilvia Veszelka, András Tóth. AB - Cell culture-based blood-brain barrier (BBB) models are useful tools for screening of CNS drug candidates. Cell sources for BBB models include primary brain endothelial cells or immortalized brain endothelial cell lines. Despite their well-known differences, epithelial cell lines are also used as surrogate models for testing neuropharmaceuticals. The aim of the present study was to compare the expression of selected BBB related genes including tight junction proteins, solute carriers (SLC), ABC transporters, metabolic enzymes and to describe the paracellular properties of nine different culture models. To establish a primary BBB model rat brain capillary endothelial cells were co-cultured with rat pericytes and astrocytes (EPA). As other BBB and surrogate models four brain endothelial cells lines, rat GP8 and RBE4 cells, and human hCMEC/D3 cells with or without lithium treatment (D3 and D3L), and four epithelial cell lines, native human intestinal Caco-2 and high P-glycoprotein expressing vinblastine-selected VB-Caco-2 cells, native MDCK and MDR1 transfected MDCK canine kidney cells were used. To test transporter functionality, the permeability of 12 molecules, glucopyranose, valproate, baclofen, gabapentin, probenecid, salicylate, rosuvastatin, pravastatin, atorvastatin, tacrine, donepezil, was also measured in the EPA and epithelial models. Among the junctional protein genes, the expression level of occludin was high in all models except the GP8 and RBE4 cells, and each model expressed a unique claudin pattern. Major BBB efflux (P-glycoprotein or ABCB1) and influx transporters (GLUT-1, LAT-1) were present in all models at mRNA levels. The transcript of BCRP (ABCG2) was not expressed in MDCK, GP8 and RBE4 cells. The absence of gene expression of important BBB efflux and influx transporters BCRP, MRP6,-9, MCT6,-8, PHT2, OATPs in one or both types of epithelial models suggests that Caco-2 or MDCK models are not suitable to test drug candidates which are substrates of these transporters. Brain endothelial cell lines GP8, RBE4, D3 and D3L did not form a restrictive paracellular barrier necessary for screening small molecular weight pharmacons. Therefore, among the tested culture models, the primary cell-based EPA model is suitable for the functional analysis of the BBB. © 2018 Veszelka, Tóth, Walter, Tóth, Gróf, Mészáros, Bocsik, Hellinger, Vastag, Rákhely and Deli. LA - English DB - MTMT ER - TY - JOUR AU - Sántha, Petra AU - Veszelka, Szilvia AU - Hoyk, Zsófia AU - Mészáros, Mária AU - Walter, Fruzsina AU - Tóth, Andrea AU - Kiss, Lóránd AU - Kincses, András AU - Oláh, Zita AU - Seprényi, György AU - Rákhely, Gábor AU - Dér, András AU - Pákáski, Magdolna AU - Kálmán, János AU - Kittel, Ágnes AU - Deli, Mária Anna TI - Restraint stress-induced morphological changes at the blood-brain barrier in adult rats JF - FRONTIERS IN MOLECULAR NEUROSCIENCE J2 - FRONT MOL NEUROSCI VL - 8 PY - 2016 PG - 15 SN - 1662-5099 DO - 10.3389/fnmol.2015.00088 UR - https://m2.mtmt.hu/api/publication/2989762 ID - 2989762 N1 - These authors have contributed equally to this work: Ágnes Kittel6 and Mária A. Deli. This study was supported by the European Union and the State of Hungary (grant nos. TÁMOP-4.2.1/B-09/1/KONV-2010-0005, TÁMOP-4.2.2.A-11/1/KONV-2012-0052, “National Excellence Program” A/2-11-1-2012-0001) and the Hungarian Research Fund (OTKA 83667). LA - English DB - MTMT ER - TY - JOUR AU - Bogár, Ferenc AU - Simon, Dóra AU - Bozsó, Zsolt AU - Janáky, Tamás AU - Veszelka, Szilvia AU - Tóth, Andrea AU - Deli, Mária Anna AU - Borics, Attila AU - Násztor, Zoltán AU - Gyebrovszki, A AU - Penke, Botond AU - Fülöp, Lívia TI - Opposite effect of Ca2+/Mg2+ ions on the aggregation of native and precursor-derived Aβ42 JF - STRUCTURAL CHEMISTRY J2 - STRUCT CHEM VL - 26 PY - 2015 IS - 5-6 SP - 1389 EP - 1403 PG - 15 SN - 1040-0400 DO - 10.1007/s11224-015-0660-2 UR - https://m2.mtmt.hu/api/publication/2942329 ID - 2942329 LA - English DB - MTMT ER - TY - JOUR AU - Lénárt, Nikolett AU - Walter, Fruzsina AU - Bocsik, Alexandra AU - Sántha, Petra AU - Tóth, Erzsébet Melinda AU - Harazin, András AU - Tóth, Andrea AU - Vizler, Csaba AU - Török, Zsolt AU - Pilbat, Ana Maria AU - Vigh, László AU - Puskás, László AU - Sántha, Miklós AU - Deli, Mária Anna TI - Cultured cells of the blood-brain barrier from apolipoprotein B-100 transgenic mice: effects of oxidized low-density lipoprotein treatment JF - FLUIDS AND BARRIERS OF THE CNS J2 - FLUIDS BARRIERS CNS VL - 12 PY - 2015 PG - 16 SN - 2045-8118 DO - 10.1186/s12987-015-0013-y UR - https://m2.mtmt.hu/api/publication/2920970 ID - 2920970 LA - English DB - MTMT ER - TY - THES AU - Tóth, Andrea TI - Protection of the blood-brain barrier under pathological conditions PB - Szegedi Tudományegyetem (SZTE) PY - 2014 SP - 57 DO - 10.14232/phd.2321 UR - https://m2.mtmt.hu/api/publication/2892871 ID - 2892871 LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Andrea AU - Tóth, András AU - Walter, Fruzsina AU - Kiss, Lóránd AU - Veszelka, Szilvia AU - Ózsvári, Béla AU - Puskás, László AU - Heimesaat, MM AU - Dohgu, S AU - Kataoka, Y AU - Rákhely, Gábor AU - Deli, Mária Anna TI - Compounds Blocking Methylglyoxal-induced Protein Modification and Brain Endothelial Injury. JF - ARCHIVES OF MEDICAL RESEARCH J2 - ARCH MED RES VL - 45 PY - 2014 IS - 8 SP - 753 EP - 764 PG - 12 SN - 0188-4409 DO - 10.1016/j.arcmed.2014.10.009 UR - https://m2.mtmt.hu/api/publication/2827332 ID - 2827332 N1 - Cited By :21 Export Date: 20 June 2022 CODEN: AEDEE AB - BACKGROUND AND AIMS: Elevated levels of reactive carbonyl species such as methylglyoxal triggers carbonyl stress and activates a series of inflammatory responses leading to accelerated vascular damage. Carbonyl stress is implicated in conditions and diseases like aging, diabetes mellitus, Alzheimer's disease and cardiovascular diseases. Our aim was to examine the effects of methylglyoxal on human hCMEC/D3 brain endothelial cells and search for protective molecules to prevent endothelial damage. METHODS: Methylglyoxal-induced modification of albumin was tested in a cell-free assay. Endothelial cell viability was monitored by impedance measurement in real-time. The following compounds were tested in cell-free and viability assays: beta-alanine, all-trans-retinoic acid, aminoguanidine, ascorbic acid, l-carnosine, GW-3333, indapamide, piracetam, gamma-tocopherol, U0126, verapamil. Barrier function of brain endothelial monolayers was characterized by resistance and permeability measurements and visualized by immunohistochemistry for beta-catenin. mRNA expression level of 60 selected blood-brain barrier-related genes in hCMEC/D3 cells was investigated by a custom Taqman gene array. RESULTS: Methylglyoxal treatment significantly elevated protein modification, exerted toxicity, reduced barrier integrity, increased permeability for markers FITC-dextran and albumin and caused higher production of reactive oxygen species in hCMEC/D3 endothelial cells. Changes in the mRNA expression of 30 genes coding tight junction proteins, transporters and enzymes were observed in methylglyoxal-treated hCMEC/D3 cells. From the tested 11 compounds only all-trans-retinoic acid, an antioxidant and anti-glycation agent, U0126, a MAP/ERK kinase inhibitor and aminoguanidine attenuated methylglyoxal-induced damage in hCMEC/D3 cells. CONCLUSIONS: All-trans-retinoic acid and inhibition of the MAP/ERK signaling pathway may be protective in carbonyl stress induced brain endothelial damage. LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Andrea AU - Walter, Fruzsina AU - Bocsik, Alexandra AU - Sántha, Petra AU - Veszelka, Szilvia AU - Nagy, Lajos István AU - Puskás, László AU - Couraud, PO AU - Takata, F AU - Dohgu, S AU - Kataoka, Y AU - Deli, Mária Anna TI - Edaravone protects against methylglyoxal-induced barrier damage in human brain endothelial cells JF - PLOS ONE J2 - PLOS ONE VL - 9 PY - 2014 IS - 7 PG - 14 SN - 1932-6203 DO - 10.1371/journal.pone.0100152 UR - https://m2.mtmt.hu/api/publication/2707330 ID - 2707330 N1 - Cited By :29 Export Date: 20 June 2022 CODEN: POLNC AB - BACKGROUND: Elevated level of reactive carbonyl species, such as methylglyoxal, triggers carbonyl stress and activates a series of inflammatory responses leading to accelerated vascular damage. Edaravone is the active substance of a Japanese medicine, which aids neurological recovery following acute brain ischemia and subsequent cerebral infarction. Our aim was to test whether edaravone can exert a protective effect on the barrier properties of human brain endothelial cells (hCMEC/D3 cell line) treated with methylglyoxal. METHODOLOGY: Cell viability was monitored in real-time by impedance-based cell electronic sensing. The barrier function of the monolayer was characterized by measurement of resistance and flux of permeability markers, and visualized by immunohistochemistry for claudin-5 and β-catenin. Cell morphology was also examined by holographic phase imaging. PRINCIPAL FINDINGS: Methylglyoxal exerted a time- and dose-dependent toxicity on cultured human brain endothelial cells: a concentration of 600 µM resulted in about 50% toxicity, significantly reduced the integrity and increased the permeability of the barrier. The cell morphology also changed dramatically: the area of cells decreased, their optical height significantly increased. Edaravone (3 mM) provided a complete protection against the toxic effect of methylglyoxal. Co-administration of edaravone restored cell viability, barrier integrity and functions of brain endothelial cells. Similar protection was obtained by the well-known antiglycating molecule, aminoguanidine, our reference compound. CONCLUSION: These results indicate for the first time that edaravone is protective in carbonyl stress induced barrier damage. Our data may contribute to the development of compounds to treat brain endothelial dysfunction in carbonyl stress related diseases. LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Andrea AU - Walter, Fruzsina AU - Bocsik, Alexandra AU - Veszelka, Szilvia AU - Nagy, Lajos István AU - Puskás, László AU - Dohgu, S AU - Watanabe, T AU - Kataoka, Y AU - Deli, Mária Anna TI - Az edaravon megvédi az agyi hajszálerek endothelsejtjeit a cukorbetegség egyik patogenetikus faktora, a metilglioxál okozta károsodástól. [Edaravone protects cerebral microvascular endothelial cells against damage caused by methylglyoxal, a pathogenic factor in diabetes mellitus] TS - [Edaravone protects cerebral microvascular endothelial cells against damage caused by methylglyoxal, a pathogenic factor in diabetes mellitus] JF - DIABETOLOGIA HUNGARICA J2 - DIABETOLOGIA HUNGARICA VL - 22 PY - 2014 SP - 138 EP - 139 PG - 2 SN - 1217-372X UR - https://m2.mtmt.hu/api/publication/2596611 ID - 2596611 LA - Hungarian DB - MTMT ER -