@article{MTMT:34691003, title = {17-Oxime ethers of oxidized ecdysteroid derivatives modulate oxidative stress in human brain endothelial cells and dose-dependently might protect or damage the blood-brain barrier}, url = {https://m2.mtmt.hu/api/publication/34691003}, author = {Vágvölgyi, Máté and Laczkó, Dávid and Santa Maria, Anaraquel and Vigh, Judit Piroska and Walter, Fruzsina and Berkecz, Róbert and Deli, Mária Anna and Tóth, Gábor and Hunyadi, Attila}, doi = {10.1371/journal.pone.0290526}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {19}, unique-id = {34691003}, issn = {1932-6203}, abstract = {20-Hydroxyecdysone and several of its oxidized derivatives exert cytoprotective effect in mammals including humans. Inspired by this bioactivity of ecdysteroids, in the current study it was our aim to prepare a set of sidechain-modified derivatives and to evaluate their potential to protect the blood-brain barrier (BBB) from oxidative stress. Six novel ecdysteroids, including an oxime and five oxime ethers, were obtained through regioselective synthesis from a sidechain-cleaved calonysterone derivative 2 and fully characterized by comprehensive NMR techniques revealing their complete 1 H and 13 C signal assignments. Surprisingly, several compounds sensitized hCMEC/D3 brain microvascular endothelial cells to tert -butyl hydroperoxide (tBHP)-induced oxidative damage as recorded by impedance measurements. Compound 8 , containing a benzyloxime ether moiety in its sidechain, was the only one that exerted a protective effect at a higher, 10 μM concentration, while at lower (10 nM– 1 μM) concentrations it promoted tBHP-induced cellular damage. Brain endothelial cells were protected from tBHP-induced barrier integrity decrease by treatment with 10 μM of compound 8 , which also mitigated the intracellular reactive oxygen species production elevated by tBHP. Based on our results, 17-oxime ethers of oxidized ecdysteroids modulate oxidative stress of the BBB in a way that may point towards unexpected toxicity. Further studies are needed to evaluate any possible risk connected to dietary ecdysteroid consumption and CNS pathologies in which BBB damage plays an important role.}, year = {2024}, eissn = {1932-6203}, orcid-numbers = {Vágvölgyi, Máté/0000-0002-2233-9422; Santa Maria, Anaraquel/0000-0003-3505-5477; Walter, Fruzsina/0000-0001-8145-2823; Berkecz, Róbert/0000-0002-9076-2177; Deli, Mária Anna/0000-0001-6084-6524; Hunyadi, Attila/0000-0003-0074-3472} } @article{MTMT:34673907, title = {Lab-on-a-chip models of the blood-brain barrier: evolution, problems, perspectives}, url = {https://m2.mtmt.hu/api/publication/34673907}, author = {Deli, Mária Anna and Porkoláb, Gergő and Kincses, András and Mészáros, Mária and Szecskó, Anikó and Kocsis, Anna and Vigh, Judit Piroska and Valkai, Sándor and Veszelka, Szilvia and Walter, Fruzsina and Dér, András}, doi = {10.1039/d3lc00996c}, journal-iso = {LAB CHIP}, journal = {LAB ON A CHIP}, volume = {24}, unique-id = {34673907}, issn = {1473-0197}, year = {2024}, eissn = {1473-0189}, pages = {1030-1063}, orcid-numbers = {Deli, Mária Anna/0000-0001-6084-6524; Valkai, Sándor/0000-0001-8479-8141; Walter, Fruzsina/0000-0001-8145-2823} } @article{MTMT:34473973, title = {Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability}, url = {https://m2.mtmt.hu/api/publication/34473973}, author = {Rust, Ruslan and Holm, Mea M. and Egger, Matteo and Weinmann, Oliver and van, Rossum Danielle and Walter, Fruzsina and Santa Maria, Anaraquel and Gronnert, Lisa and Maurer, Michael A. and Kraler, Simon and Akhmedov, Alexander and Cideciyan, Rose and Luscher, Thomas F. and Deli, Mária Anna and Herrmann, Inge K. and Schwab, Martin E.}, doi = {10.1177/0271678X231216270}, journal-iso = {J CEREBR BLOOD F MET}, journal = {JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM}, unique-id = {34473973}, issn = {0271-678X}, abstract = {Nogo-A is a transmembrane protein with multiple functions in the central nervous system (CNS), including restriction of neurite growth and synaptic plasticity. Thus far, Nogo-A has been predominantly considered a cell contact-dependent ligand signaling via cell surface receptors. Here, we show that Nogo-A can be secreted by cultured cells of neuronal and glial origin in association with extracellular vesicles (EVs). Neuron- and oligodendrocyte-derived Nogo-A containing EVs inhibited fibroblast spreading, and this effect was partially reversed by Nogo-A receptor S1PR2 blockage. EVs purified from HEK cells only inhibited fibroblast spreading upon Nogo-A over-expression. Nogo-A-containing EVs were found in vivo in the blood of healthy mice and rats, as well as in human plasma. Blood Nogo-A concentrations were elevated after acute stroke lesions in mice and rats. Nogo-A active peptides decreased barrier integrity in an in vitro blood-brain barrier model. Stroked mice showed increased dye permeability in peripheral organs when tested 2 weeks after injury. In the Miles assay, an in vivo test to assess leakage of the skin vasculature, a Nogo-A active peptide increased dye permeability. These findings suggest that blood borne, possibly EV-associated Nogo-A could exert long-range regulatory actions on vascular permeability.}, keywords = {INHIBITION; NEURITE OUTGROWTH; PROTEINS; SYNAPTIC PLASTICITY; Hematology; Blood-Brain Barrier; stroke; Exosomes; Exosomes; nanoparticle tracking analysis; Endocrinology & Metabolism; axonal regeneration; BRAIN-BARRIER; Nogo-A; Corticospinal tract; S1PR2}, year = {2024}, eissn = {1559-7016}, orcid-numbers = {Rust, Ruslan/0000-0003-3376-3453; Walter, Fruzsina/0000-0001-8145-2823; Santa Maria, Anaraquel/0000-0003-3505-5477; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:33688148, title = {The Use of Sensors in Blood-Brain Barrier-on-a-Chip Devices: Current Practice and Future Directions}, url = {https://m2.mtmt.hu/api/publication/33688148}, author = {Kincses, András and Vigh, Judit Piroska and Petrovszki, Dániel and Valkai, Sándor and Kocsis, Anna and Walter, Fruzsina and Lin, Hung-Yin and Jan, Jeng-Shiung and Deli, Mária Anna and Dér, András}, doi = {10.3390/bios13030357}, journal-iso = {BIOSENSORS-BASEL}, journal = {BIOSENSORS}, volume = {13}, unique-id = {33688148}, abstract = {The application of lab-on-a-chip technologies in in vitro cell culturing swiftly resulted in improved models of human organs compared to static culture insert-based ones. These chip devices provide controlled cell culture environments to mimic physiological functions and properties. Models of the blood-brain barrier (BBB) especially profited from this advanced technological approach. The BBB represents the tightest endothelial barrier within the vasculature with high electric resistance and low passive permeability, providing a controlled interface between the circulation and the brain. The multi-cell type dynamic BBB-on-chip models are in demand in several fields as alternatives to expensive animal studies or static culture inserts methods. Their combination with integrated biosensors provides real-time and noninvasive monitoring of the integrity of the BBB and of the presence and concentration of agents contributing to the physiological and metabolic functions and pathologies. In this review, we describe built-in sensors to characterize BBB models via quasi-direct current and electrical impedance measurements, as well as the different types of biosensors for the detection of metabolites, drugs, or toxic agents. We also give an outlook on the future of the field, with potential combinations of existing methods and possible improvements of current techniques.}, year = {2023}, eissn = {2079-6374}, orcid-numbers = {Valkai, Sándor/0000-0001-8479-8141; Walter, Fruzsina/0000-0001-8145-2823; Jan, Jeng-Shiung/0000-0002-8379-404X; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:33688118, title = {Role of interleukin-6 and interleukin-10 in morphological and functional changes of the blood–brain barrier in hypertriglyceridemia}, url = {https://m2.mtmt.hu/api/publication/33688118}, author = {Barabási, Beáta and Barna, Lilla and Santa Maria, Anaraquel and Harazin, András and Molnár, Réka and Kincses, András and Vigh, Judit Piroska and Dukay, Brigitta and Sántha, Miklós and Tóth, Erzsébet Melinda and Walter, Fruzsina and Deli, Mária Anna and Hoyk, Zsófia}, doi = {10.1186/s12987-023-00418-3}, journal-iso = {FLUIDS BARRIERS CNS}, journal = {FLUIDS AND BARRIERS OF THE CNS}, volume = {20}, unique-id = {33688118}, issn = {2045-8118}, year = {2023}, eissn = {2045-8118}, orcid-numbers = {Santa Maria, Anaraquel/0000-0003-3505-5477; Harazin, András/0000-0002-0904-5606; Molnár, Réka/0000-0002-3128-825X; Walter, Fruzsina/0000-0001-8145-2823; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:33641697, title = {Highly Oxidized Ecdysteroids from a Commercial Cyanotis arachnoidea Root Extract as Potent Blood-Brain Barrier Protective Agents}, url = {https://m2.mtmt.hu/api/publication/33641697}, author = {Tóth, Gábor and Santa Maria, Anaraquel and Herke, Ibolya and Gáti, Tamás and Galvis-Montes, Daniel and Walter, Fruzsina and Deli, Mária Anna and Hunyadi, Attila}, doi = {10.1021/acs.jnatprod.2c00948}, journal-iso = {J NAT PROD}, journal = {JOURNAL OF NATURAL PRODUCTS}, volume = {86}, unique-id = {33641697}, issn = {0163-3864}, year = {2023}, eissn = {1520-6025}, pages = {1074-1080}, orcid-numbers = {Santa Maria, Anaraquel/0000-0003-3505-5477; Walter, Fruzsina/0000-0001-8145-2823; Deli, Mária Anna/0000-0001-6084-6524; Hunyadi, Attila/0000-0003-0074-3472} } @article{MTMT:33621088, title = {Targeting Human Endothelial Cells with Glutathione and Alanine Increases the Crossing of a Polypeptide Nanocarrier through a Blood–Brain Barrier Model and Entry to Human Brain Organoids}, url = {https://m2.mtmt.hu/api/publication/33621088}, author = {Mészáros, Mária and Phan, Thi Ha My and Vigh, Judit Piroska and Porkoláb, Gergő and Kocsis, Anna and Páli, Emese K. and Polgár, Tamás Ferenc and Walter, Fruzsina and Bolognin, Silvia and Schwamborn, Jens C. and Jan, Jeng-Shiung and Deli, Mária Anna and Veszelka, Szilvia}, doi = {10.3390/cells12030503}, journal-iso = {CELLS-BASEL}, journal = {CELLS}, volume = {12}, unique-id = {33621088}, abstract = {Nanoparticles (NPs) are the focus of research efforts that aim to develop successful drug delivery systems for the brain. Polypeptide nanocarriers are versatile platforms and combine high functionality with good biocompatibility and biodegradability. The key to the efficient brain delivery of NPs is the specific targeting of cerebral endothelial cells that form the blood–brain barrier (BBB). We have previously discovered that the combination of two different ligands of BBB nutrient transporters, alanine and glutathione, increases the permeability of vesicular NPs across the BBB. Our aim here was to investigate whether the combination of these molecules can also promote the efficient transfer of 3-armed poly(l-glutamic acid) NPs across a human endothelial cell and brain pericyte BBB co-culture model. Alanine and glutathione dual-targeted polypeptide NPs showed good cytocompatibility and elevated cellular uptake in a time-dependent and active manner. Targeted NPs had a higher permeability across the BBB model and could subsequently enter midbrain-like organoids derived from healthy and Parkinson’s disease patient-specific stem cells. These results indicate that poly(l-glutamic acid) NPs can be used as nanocarriers for nervous system application and that the right combination of molecules that target cerebral endothelial cells, in this case alanine and glutathione, can facilitate drug delivery to the brain.}, year = {2023}, eissn = {2073-4409}, orcid-numbers = {Walter, Fruzsina/0000-0001-8145-2823; Bolognin, Silvia/0000-0002-1399-2999; Jan, Jeng-Shiung/0000-0002-8379-404X; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:32917592, title = {Effects of fasudil on blood-brain barrier integrity}, url = {https://m2.mtmt.hu/api/publication/32917592}, author = {Sato, Kei and Nakagawa, Shinsuke and Morofuji, Yoichi and Matsunaga, Yuki and Fujimoto, Takashi and Watanabe, Daisuke and Izumo, Tsuyoshi and Niwa, Masami and Walter, Fruzsina and Vigh, Judit Piroska and Santa Maria, Anaraquel and Deli, Mária Anna and Matsuo, Takayuki}, doi = {10.1186/s12987-022-00336-w}, journal-iso = {FLUIDS BARRIERS CNS}, journal = {FLUIDS AND BARRIERS OF THE CNS}, volume = {19}, unique-id = {32917592}, issn = {2045-8118}, abstract = {Background Cerebral infarction accounts for 85% of all stroke cases. Even in an era of rapid and effective recanalization using an intravascular approach, the majority of patients have poor functional outcomes. Thus, there is an urgent need for the development of therapeutic agents to treat acute ischemic stroke. We evaluated the effect of fasudil, a Rho kinase inhibitor, on blood brain barrier (BBB) functions under normoxia or oxygen-glucose deprivation (OGD) conditions using a primary cell-based in vitro BBB model. Methods BBB models from rat primary cultures (brain capillary endothelial cells, astrocytes, and pericytes) were subjected to either normoxia or 6 h OGD/24 h reoxygenation. To assess the effects of fasudil on BBB functions, we evaluated real time impedance, transendothelial electrical resistance (TEER), sodium fluorescein permeability, and tight junction protein expression using western blotting. Lastly, to understand the observed protective mechanism on BBB functions by fasudil we examined the role of cyclooxygenase-2 and thromboxane A2 receptor agonist U-46619 in BBB-forming cells. Results We found that treatment with 0.3-30 mu M of fasudil increased cellular impedance. Fasudil enhanced barrier properties in a concentration-dependent manner, as measured by an increased (TEER) and decreased permeability. Fasudil also increased the expression of tight junction protein claudin-5. Reductions in TEER and increased permeability were observed after OGD/reoxygenation exposure in mono- and co-culture models. The improvement in BBB integrity by fasudil was confirmed in both of the models, but was significantly higher in the co-culture than in the monoculture model. Treatment with U-46619 did not show significant changes in TEER in the monoculture model, whereas it showed a significant reduction in TEER in the co-culture model. Fasudil significantly improved the U-46619-induced TEER reduction in the co-culture models. Pericytes and astrocytes have opposite effects on endothelial cells and may contribute to endothelial injury in hyperacute ischemic stroke. Overall, fasudil protects the integrity of BBB both by a direct protective effect on endothelial cells and by a pathway mediated via pericytes and astrocytes. Conclusions Our findings suggest that fasudil is a BBB-protective agent against acute ischemic stroke.}, keywords = {INHIBITION; CLEAVAGE; INJURY; ACTIVATION; ASTROCYTES; RHO-ASSOCIATED KINASE; Blood-Brain Barrier; ISCHEMIC-STROKE; tight junction; Thrombectomy; Acute ischemic stroke; pericytes; pericytes; fasudil; RHO-KINASE INHIBITOR; Oxygen-glucose deprivation-reoxygenation; CEREBRAL BARRIER}, year = {2022}, eissn = {2045-8118}, orcid-numbers = {Morofuji, Yoichi/0000-0001-7135-2220; Walter, Fruzsina/0000-0001-8145-2823; Santa Maria, Anaraquel/0000-0003-3505-5477; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:32667372, title = {Blood–brain barrier dysfunction in l-ornithine induced acute pancreatitis in rats and the direct effect of l-ornithine on cultured brain endothelial cells}, url = {https://m2.mtmt.hu/api/publication/32667372}, author = {Walter, Fruzsina and Harazin, András and Tóth, Andrea and Veszelka, Szilvia and Santa Maria, Anaraquel and Barna, Lilla and Kincses, András and Biczo, G and Balla, Zsolt and Kui, Balázs and Maléth, József and Cervenak, László and Tubak, Vilmos and Kittel, Ágnes and Rakonczay, Zoltán and Deli, Mária Anna}, doi = {10.1186/s12987-022-00308-0}, journal-iso = {FLUIDS BARRIERS CNS}, journal = {FLUIDS AND BARRIERS OF THE CNS}, volume = {19}, unique-id = {32667372}, issn = {2045-8118}, year = {2022}, eissn = {2045-8118}, orcid-numbers = {Walter, Fruzsina/0000-0001-8145-2823; Harazin, András/0000-0002-0904-5606; Santa Maria, Anaraquel/0000-0003-3505-5477; Maléth, József/0000-0001-5768-3090; Cervenak, László/0000-0003-0166-8697; Tubak, Vilmos/0000-0002-6141-3920; Rakonczay, Zoltán/0000-0002-1499-3416; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:32602220, title = {Penetration of the SARS-CoV-2 Spike Protein across the Blood–Brain Barrier, as Revealed by a Combination of a Human Cell Culture Model System and Optical Biosensing}, url = {https://m2.mtmt.hu/api/publication/32602220}, author = {Petrovszki, Dániel and Walter, Fruzsina and Vigh, Judit Piroska and Kocsis, Anna and Valkai, Sándor and Deli, Mária Anna and Dér, András}, doi = {10.3390/biomedicines10010188}, journal-iso = {BIOMEDICINES}, journal = {BIOMEDICINES}, volume = {10}, unique-id = {32602220}, year = {2022}, eissn = {2227-9059}, orcid-numbers = {Walter, Fruzsina/0000-0001-8145-2823; Valkai, Sándor/0000-0001-8479-8141; Deli, Mária Anna/0000-0001-6084-6524} }