@article{CramerTackeBornhorstetal.2014,
  author    = {Cramer, Sandra and Tacke, Sebastian and Bornhorst, Julia and Klingauf, J{\"u}rgen and Schwerdtle, Tanja and Galla, Hans-Joachim},
  title     = {The Influence of Silver Nanoparticles on the Blood-Brain and the Blood-Cerebrospinal Fluid Barrier in vitro},
  series = {Journal of Nanomedicine \& Nanotechnology},
  volume    = {5},
  journal   = {Journal of Nanomedicine \& Nanotechnology},
  number    = {5},
  issn      = {2157-7439},
  doi       = {10.4172/2157-7439.1000225},
  pages     = {12},
  year      = {2014},
  abstract  = {The use of silver nanoparticles in medical and consumer products such as wound dressings, clothing and cosmetic has increased significantly in recent years. Still, the influence of these particles on our health and especially on our brain, has not been examined adequately up to now. We studied the influence of AgEO- (Ethylene Oxide) and AgCitrate-Nanoparticles (NPs) on the protective barriers of the brain, namely the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (blood-CSF) barrier in vitro. The NPs toxicity was evaluated by examining changes in membrane integrity, cell morphology, barrier properties, oxidative stress and inflammatory reactions. AgNPs decreased cell viability, disturbed barrier integrity and tight junctions and triggered oxidative stress and DNA strand breaks. However, all mentioned effects were, at least partly, suppressed by a Citrate-coating and were most pronounced in the cells of the BBB as compared to the epithelial cells representing the blood-CSF barrier. AgEO- but not AgCitrate-NPs also triggered an inflammatory reaction in porcine brain capillary endothelial cells (PBCEC), which represent the BBB. Our data indicate that AgNPs may cause adverse effects within the barriers of the brain, but their toxicity can be reduced by choosing an appropriate coating material.},
  language  = {en}
}
@article{LohrenBornhorstFitkauetal.2016,
  author    = {Lohren, Hanna and Bornhorst, Julia and Fitkau, Romy and Pohl, Gabriele and Galla, Hans-Joachim and Schwerdtle, Tanja},
  title     = {Effects on and transfer across the blood-brain barrier in vitro-Comparison of organic and inorganic mercury species},
  series = {BMC pharmacology \& toxicology},
  volume    = {17},
  journal   = {BMC pharmacology \& toxicology},
  publisher = {BioMed Central},
  address   = {London},
  issn      = {2050-6511},
  doi       = {10.1186/s40360-016-0106-5},
  pages     = {422 -- 433},
  year      = {2016},
  abstract  = {Background: Transport of methylmercury (MeHg) across the blood-brain barrier towards the brain side is well discussed in literature, while ethylmercury (EtHg) and inorganic mercury are not adequately characterized regarding their entry into the brain. Studies investigating a possible efflux out of the brain are not described to our knowledge. Methods: This study compares, for the first time, effects of organic methylmercury chloride (MeHgCl), EtHg-containing thiomersal and inorganic Hg chloride (HgCl2) on as well as their transfer across a primary porcine in vitro model of the blood-brain barrier. Results: With respect to the barrier integrity, the barrier model exhibited a much higher sensitivity towards HgCl2 following basolateral incubation (brain-facing side) as compared to apical application (blood-facing side). These HgCl2 induced effects on the barrier integrity after brain side incubation are comparable to that of the organic species, although MeHgCl and thiomersal exerted much higher cytotoxic effects in the barrier building cells. Hg transfer rates following exposure to organic species in both directions argue for diffusion as transfer mechanism. Inorganic Hg application surprisingly resulted in a Hg transfer out of the brain-facing compartment. Conclusions: In case of MeHgCl and thiomersal incubation, mercury crossed the barrier in both directions, with a slight accumulation in the basolateral, brain-facing compartment, after simultaneous incubation in both compartments. For HgCl2, our data provide first evidence that the blood-brain barrier transfers mercury out of the brain.},
  language  = {en}
}
@misc{LohrenBornhorstFitkauetal.2017,
  author    = {Lohren, Hanna and Bornhorst, Julia and Fitkau, Romy and Pohl, Gabriele and Galla, Hans-Joachim and Schwerdtle, Tanja},
  title     = {Effects on and transfer across the blood-brain barrier in vitro},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-401776},
  pages     = {11},
  year      = {2017},
  abstract  = {Background: Transport of methylmercury (MeHg) across the blood-brain barrier towards the brain side is well discussed in literature, while ethylmercury (EtHg) and inorganic mercury are not adequately characterized regarding their entry into the brain. Studies investigating a possible efflux out of the brain are not described to our knowledge. Methods: This study compares, for the first time, effects of organic methylmercury chloride (MeHgCl), EtHg-containing thiomersal and inorganic Hg chloride (HgCl2) on as well as their transfer across a primary porcine in vitro model of the blood-brain barrier. Results: With respect to the barrier integrity, the barrier model exhibited a much higher sensitivity towards HgCl2 following basolateral incubation (brain-facing side) as compared to apical application (blood-facing side). These HgCl2 induced effects on the barrier integrity after brain side incubation are comparable to that of the organic species, although MeHgCl and thiomersal exerted much higher cytotoxic effects in the barrier building cells. Hg transfer rates following exposure to organic species in both directions argue for diffusion as transfer mechanism. Inorganic Hg application surprisingly resulted in a Hg transfer out of the brain-facing compartment. Conclusions: In case of MeHgCl and thiomersal incubation, mercury crossed the barrier in both directions, with a slight accumulation in the basolateral, brain-facing compartment, after simultaneous incubation in both compartments. For HgCl2, our data provide first evidence that the blood-brain barrier transfers mercury out of the brain.},
  language  = {en}
}
@article{LohrenBornhorstGallaetal.2015,
  author    = {Lohren, Hanna and Bornhorst, Julia and Galla, Hans-Joachim and Schwerdtle, Tanja},
  title     = {The blood-cerebrospinal fluid barrier},
  series = {Metallomics : integrated biometal science},
  volume    = {10},
  journal   = {Metallomics : integrated biometal science},
  number    = {7},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {1756-5901},
  doi       = {10.1039/C5MT00171D},
  pages     = {1420 -- 1430},
  year      = {2015},
  abstract  = {Exposure to organic mercury compounds promotes primarily neurological effects. Although methylmercury is recognized as a potent neurotoxicant, its transfer into the central nervous system (CNS) is not fully evaluated. While methylmercury and thiomersal pass the blood-brain barrier, limited data are available regarding the second brain regulating interface, the blood-cerebrospinal fluid (CSF) barrier. This novel study was designed to investigate the effects of organic as well as inorganic mercury compounds on, and their transfer across, a porcine in vitro model of the blood-CSF barrier for the first time. The barrier system is significantly more sensitive towards organic Hg compounds as compared to inorganic compounds regarding the endpoints cytotoxicity and barrier integrity. Whereas there are low transfer rates from the blood side to the CSF side, our results strongly indicate an active transfer of the organic mercury compounds out of the CSF. These results are the first to demonstrate an efflux of organic mercury compounds regarding the CNS and provide a completely new approach in the understanding of mercury compounds specific transport.},
  language  = {en}
}
@misc{LohrenBornhorstGallaetal.2015,
  author    = {Lohren, Hanna and Bornhorst, Julia and Galla, Hans-Joachim and Schwerdtle, Tanja},
  title     = {The blood-cerebrospinal fluid barrier},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-82089},
  year      = {2015},
  abstract  = {Exposure to organic mercury compounds promotes primarily neurological effects. Although methylmercury is recognized as a potent neurotoxicant, its transfer into the central nervous system (CNS) is not fully evaluated. While methylmercury and thiomersal pass the blood-brain barrier, limited data are available regarding the second brain regulating interface, the blood-cerebrospinal fluid (CSF) barrier. This novel study was designed to investigate the effects of organic as well as inorganic mercury compounds on, and their transfer across, a porcine in vitro model of the blood-CSF barrier for the first time. The barrier system is significantly more sensitive towards organic Hg compounds as compared to inorganic compounds regarding the endpoints cytotoxicity and barrier integrity. Whereas there are low transfer rates from the blood side to the CSF side, our results strongly indicate an active transfer of the organic mercury compounds out of the CSF. These results are the first to demonstrate an efflux of organic mercury compounds regarding the CNS and provide a completely new approach in the understanding of mercury compounds specific transport.},
  language  = {en}
}
@article{LohrenBornhorstGallaetal.2015,
  author    = {Lohren, Hanna and Bornhorst, Julia and Galla, Hans-Joachim and Schwerdtle, Tanja},
  title     = {The blood-cerebrospinal fluid barrier - first evidence for an active transport of organic mercury compounds out of the brain},
  series = {Metallomics : integrated biometal science},
  volume    = {7},
  journal   = {Metallomics : integrated biometal science},
  number    = {10},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {1756-5901},
  doi       = {10.1039/c5mt00171d},
  pages     = {1420 -- 1430},
  year      = {2015},
  abstract  = {Exposure to organic mercury compounds promotes primarily neurological effects. Although methylmercury is recognized as a potent neurotoxicant, its transfer into the central nervous system (CNS) is not fully evaluated. While methylmercury and thiomersal pass the blood-brain barrier, limited data are available regarding the second brain regulating interface, the blood-cerebrospinal fluid (CSF) barrier. This novel study was designed to investigate the effects of organic as well as inorganic mercury compounds on, and their transfer across, a porcine in vitro model of the blood-CSF barrier for the first time. The barrier system is significantly more sensitive towards organic Hg compounds as compared to inorganic compounds regarding the endpoints cytotoxicity and barrier integrity. Whereas there are low transfer rates from the blood side to the CSF side, our results strongly indicate an active transfer of the organic mercury compounds out of the CSF. These results are the first to demonstrate an efflux of organic mercury compounds regarding the CNS and provide a completely new approach in the understanding of mercury compounds specific transport.},
  language  = {en}
}
@article{MuellerEbertBornhorstetal.2018,
  author    = {M{\"u}ller, Sandra Marie and Ebert, Franziska and Bornhorst, Julia and Galla, Hans-Joachim and Francesconi, Kevin A. and Schwerdtle, Tanja},
  title     = {Arsenic-containing hydrocarbons disrupt a model in vitro blood-cerebrospinal fluid barrier},
  series = {Journal of trace elements in medicine and biology},
  volume    = {49},
  journal   = {Journal of trace elements in medicine and biology},
  publisher = {Elsevier GMBH},
  address   = {M{\"u}nchen},
  issn      = {0946-672X},
  doi       = {10.1016/j.jtemb.2018.01.020},
  pages     = {171 -- 177},
  year      = {2018},
  abstract  = {Lipid-soluble arsenicals, so-called arsenolipids, have gained a lot of attention in the last few years because of their presence in many seafoods and reports showing substantial cytotoxicity emanating from arsenic-containing hydrocarbons (AsHCs), a prominent subgroup of the arsenolipids. More recent in vivo and in vitro studies indicate that some arsenolipids might have adverse effects on brain health. In the present study, we focused on the effects of selected arsenolipids and three representative metabolites on the blood-cerebrospinal fluid barrier (B-CSF-B), a brain-regulating interface. For this purpose, we incubated an in vitro model of the B-CSF-B composed of porcine choroid plexus epithelial cells (PCPECs) with three AsHCs, two arsenic-containing fatty acids (AsFAs) and three representative arsenolipid metabolites (dimethylarsinic acid, thio/oxo-dimethylpropanoic acid) to examine their cytotoxic potential and impact on barrier integrity. The toxic arsenic species arsenite was also tested in this way and served as a reference substance. While AsFAs and the metabolites showed no cytotoxic effects in the conducted assays, AsHCs showed a strong cytotoxicity, being up to 1.5-fold more cytotoxic than arsenite. Analysis of the in vitro B-CSF-B integrity showed a concentration dependent disruption of the barrier within 72 h. The correlation with the decreased plasma membrane surface area (measured as capacitance) indicates cytotoxic effects. These findings suggest exposure to elevated levels of certain arsenolipids may have detrimental consequences for the central nervous system.},
  language  = {en}
}
@article{MuellerEbertRaberetal.2018,
  author    = {M{\"u}ller, Sandra Marie and Ebert, Franziska and Raber, Georg and Meyer, S{\"o}ren and Bornhorst, Julia and H{\"u}wel, Stephan and Galla, Hans-Joachim and Francesconi, Kevin A. and Schwerdtle, Tanja},
  title     = {Effects of arsenolipids on in vitro blood-brain barrier model},
  series = {Archives of toxicology : official journal of EUROTOX},
  volume    = {92},
  journal   = {Archives of toxicology : official journal of EUROTOX},
  number    = {2},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {0340-5761},
  pages     = {823 -- 832},
  year      = {2018},
  abstract  = {Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids (AsLs) occurring in fish and edible algae, possess a substantial neurotoxic potential in fully differentiated human brain cells. Previous in vivo studies indicating that AsHCs cross the blood-brain barrier of the fruit fly Drosophila melanogaster raised the question whether AsLs could also cross the vertebrate blood-brain barrier (BBB). In the present study, we investigated the impact of several representatives of AsLs (AsHC 332, AsHC 360, AsHC 444, and two arsenic-containing fatty acids, AsFA 362 and AsFA 388) as well as of their metabolites (thio/oxo-dimethylpropionic acid, dimethylarsinic acid) on porcine brain capillary endothelial cells (PBCECs, in vitro model for the blood-brain barrier). AsHCs exerted the strongest cytotoxic effects of all investigated arsenicals as they were up to fivefold more potent than the toxic reference species arsenite (iAsIII). In our in vitro BBB-model, we observed a slight transfer of AsHC 332 across the BBB after 6 h at concentrations that do not affect the barrier integrity. Furthermore, incubation with AsHCs for 72 h led to a disruption of the barrier at sub-cytotoxic concentrations. The subsequent immunocytochemical staining of three tight junction proteins revealed a significant impact on the cell membrane. Because AsHCs enhance the permeability of the in vitro blood-brain barrier, a similar behavior in an in vivo system cannot be excluded. Consequently, AsHCs might facilitate the transfer of accompanying foodborne toxicants into the brain.},
  language  = {en}
}
@article{PieperMarekUnterbergetal.2014,
  author    = {Pieper, Christian and Marek, Jasmin Jacqueline and Unterberg, Marlies and Schwerdtle, Tanja and Galla, Hans-Joachim},
  title     = {Brain capillary pericytes contribute to the immune defense in response to cytokines or LPS in vitro},
  series = {Brain research : an international multidisciplinary journal devoted to fundamental research in the brain sciences},
  volume    = {1550},
  journal   = {Brain research : an international multidisciplinary journal devoted to fundamental research in the brain sciences},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {0006-8993},
  doi       = {10.1016/j.brainres.2014.01.004},
  pages     = {1 -- 8},
  year      = {2014},
  abstract  = {The prevention of an inflammation in the brain is one of the most important goals the body has to achieve. As pericytes are located on the abluminal side of the capillaries in the brain, their role in fighting against invading pathogens has been investigated in some points, mostly in their ability to behave like macrophages. Here we studied the potential of pericytes to react as immune cells under inflammatory conditions, especially regarding the expression of the inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), major histocompatibility complex II (MHC II) molecules, CD68, as well as the generation of reactive oxygen and nitrogen species (RONS), and their ability in phagocytosis. Quantitative real time PCR and western blot analysis showed that pericytes are able to increase the expression of typical inflammatory marker proteins after the stimulation with tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1 beta), interferon-gamma (IFN-gamma), or lipopolysaccharides (LPS). Depending on the different specific pro-inflammatory factors pericytes changed the expression of alpha smooth muscle actin (alpha SMA), the most predominant pericyte marker. We conclude that the role of the pericytes within the immune system is regulated and fine-tuned by different cytokines strongly depending on the time when the cytokines are released and their concentration. The present results will help to understand the pericyte mediated defense mechanisms in the brain.},
  language  = {en}
}
@article{StrehlauWeberLuerenbaumetal.2017,
  author    = {Strehlau, Jenny and Weber, Till and Luerenbaum, Constantin and Bornhorst, Julia and Galla, Hans-Joachim and Schwerdtle, Tanja and Winter, Martin and Nowak, Sascha},
  title     = {Towards quantification of toxicity of lithium ion battery electrolytes - development and validation of a liquid-liquid extraction GC-MS method for the determination of organic carbonates in cell culture materials},
  series = {Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry, Analusis and Quimica analitica},
  volume    = {409},
  journal   = {Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry, Analusis and Quimica analitica},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {1618-2642},
  doi       = {10.1007/s00216-017-0549-6},
  pages     = {6123 -- 6131},
  year      = {2017},
  abstract  = {A novel method based on liquid-liquid extraction with subsequent gas chromatography separation and mass spectrometric detection (GC-MS) for the quantification of organic carbonates in cell culture materials is presented. Method parameters including the choice of extraction solvent, of extraction method and of extraction time were optimised and the method was validated. The setup allowed for determination within a linear range of more than two orders of magnitude. The limits of detection (LODs) were between 0.0002 and 0.002 mmol/L and the repeatability precisions were in the range of 1.5-12.9\%. It could be shown that no matrix effects were present and recovery rates between 98 and 104\% were achieved. The methodology was applied to cell culture models incubated with commercial lithium ion battery (LIB) electrolytes to gain more insight into the potential toxic effects of these compounds. The stability of the organic carbonates in cell culture medium after incubation was studied. In a porcine model of the blood-cerebrospinal fluid (CSF) barrier, it could be shown that a transfer of organic carbonates into the brain facing compartment took place.},
  language  = {en}
}