@article{ShityakovSalvadorPastorinetal.2015,
  author    = {Shityakov, Sergey and Salvador, Ellaine and Pastorin, Giorgia and F{\"o}rster, Carola},
  title     = {Blood-brain barrier transport studies, aggregation, and molecular dynamics simulation of multiwalled carbon nanotube functionalized with fluorescein isothiocyanate},
  series = {International Journal of Nanomedicine},
  volume    = {10},
  journal   = {International Journal of Nanomedicine},
  doi       = {10.2147/IJN.S68429},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149233},
  pages     = {1703-1713},
  year      = {2015},
  abstract  = {In this study, the ability of a multiwalled carbon nanotube functionalized with fluorescein isothiocyanate (MWCNT-FITC) was assessed as a prospective central nervous system-targeting drug delivery system to permeate the blood-brain barrier. The results indicated that the MWCNT-FITC conjugate is able to penetrate microvascular cerebral endothelial monolayers; its concentrations in the Transwell® system were fully equilibrated after 48 hours. Cell viability test, together with phase-contrast and fluorescence microscopies, did not detect any signs of MWCNT-FITC toxicity on the cerebral endothelial cells. These microscopic techniques also revealed presumably the intracellular localization of fluorescent MWCNT-FITCs apart from their massive nonfluorescent accumulation on the cellular surface due to nanotube lipophilic properties. In addition, the 1,000 ps molecular dynamics simulation in vacuo discovered the phenomenon of carbon nanotube aggregation driven by van der Waals forces via MWCN-TFITC rapid dissociation as an intermediate phase.},
  language  = {en}
}
@article{SalvadorShityakovFoerster2013,
  author    = {Salvador, Ellaine and Shityakov, Sergey and F{\"o}rster, Carola},
  title     = {Glucocorticoids and endothelial cell barrier function},
  series = {Cell and Tissue Research},
  volume    = {355},
  journal   = {Cell and Tissue Research},
  number    = {3},
  doi       = {10.1007/s00441-013-1762-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132091},
  pages     = {597-605},
  year      = {2013},
  abstract  = {Glucocorticoids (GCs) are steroid hormones that have inflammatory and immunosuppressive effects on a wide variety of cells. They are used as therapy for inflammatory disease and as a common agent against edema. The blood brain barrier (BBB), comprising microvascular endothelial cells, serves as a permeability screen between the blood and the brain. As such, it maintains homeostasis of the central nervous system (CNS). In many CNS disorders, BBB integrity is compromised. GC treatment has been demonstrated to improve the tightness of the BBB. The responses and effects of GCs are mediated by the ubiquitous GC receptor (GR). Ligand-bound GR recognizes and binds to the GC response element located within the promoter region of target genes. Transactivation of certain target genes leads to improved barrier properties of endothelial cells. In this review, we deal with the role of GCs in endothelial cell barrier function. First, we describe the mechanisms of GC action at the molecular level. Next, we discuss the regulation of the BBB by GCs, with emphasis on genes targeted by GCs such as occludin, claudins and VE-cadherin. Finally, we present currently available GC therapeutic strategies and their limitations.},
  language  = {en}
}
@article{ShityakovPuskasPapaietal.2015,
  author    = {Shityakov, Sergey and Pusk{\´a}s, Istv{\´a}n and P{\´a}pai, Katalin and Salvador, Ellaine and Roewer, Norbert and F{\"o}rster, Carola and Broscheit, Jens-Albert},
  title     = {Sevoflurane-sulfobutylether-\(\beta\)-cyclodextrin complex: preparation, characterization, cellular toxicity, molecular modeling and blood-brain barrier transport studies},
  series = {Molecules},
  volume    = {20},
  journal   = {Molecules},
  doi       = {10.3390/molecules200610264},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148543},
  pages     = {10264-10279},
  year      = {2015},
  abstract  = {The objective of the present investigation was to study the ability of sulfobutylether-\(\beta\)-cyclodextrin (SBECD) to form an inclusion complex with sevoflurane (SEV), a volatile anesthetic with poor water solubility. The inclusion complex was prepared, characterized and its cellular toxicity and blood-brain barrier (BBB) permeation potential of the formulated SEV have also been examined for the purpose of controlled drug delivery. The SEV-SBE\(\beta\)CD complex was nontoxic to the primary brain microvascular endothelial (pEND) cells at a clinically relevant concentration of sevoflurane. The inclusion complex exhibited significantly higher BBB permeation profiles as compared with the reference substance (propranolol) concerning calculated apparent permeability values (P\(_{app}\)). In addition, SEV binding affinity to SBE\(\beta\)CD was confirmed by a minimal Gibbs free energy of binding (ΔG\(_{bind}\)) value of -1.727 ± 0.042 kcal・mol\(^{-1}\) and an average binding constant (K\(_{b}\)) of 53.66 ± 9.24 mM indicating rapid drug liberation from the cyclodextrin amphiphilic cavity.},
  language  = {en}
}
@article{RoesingSalvadorGuentzeletal.2020,
  author    = {R{\"o}sing, Nils and Salvador, Ellaine and G{\"u}ntzel, Paul and Kempe, Christoph and Burek, Malgorzata and Holzgrabe, Ulrike and Soukhoroukov, Vladimir and Wunder, Christian and F{\"o}rster, Carola},
  title     = {Neuroprotective Effects of Isosteviol Sodium in Murine Brain Capillary Cerebellar Endothelial Cells (cerebEND) After Hypoxia},
  series = {Frontiers in Cellular Neuroscience},
  volume    = {14},
  journal   = {Frontiers in Cellular Neuroscience},
  issn      = {1662-5102},
  doi       = {10.3389/fncel.2020.573950},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215013},
  year      = {2020},
  abstract  = {Ischemic stroke is one of the leading causes of death worldwide. It damages neurons and other supporting cellular elements in the brain. However, the impairment is not only confined to the region of assault but the surrounding area as well. Besides, it also brings about damage to the blood-brain barrier (BBB) which in turn leads to microvascular failure and edema. Hence, this necessitates an on-going, continuous search for intervention strategies and effective treatment. Of late, the natural sweetener stevioside proved to exhibit neuroprotective effects and therapeutic benefits against cerebral ischemia-induced injury. Its injectable formulation, isosteviol sodium (STVNA) also demonstrated favorable results. Nonetheless, its effects on the BBB have not yet been investigated to date. As such, this present study was designed to assess the effects of STVNA in our in vitro stroke model of the BBB.The integrity and permeability of the BBB are governed and maintained by tight junction proteins (TJPs) such as claudin-5 and occludin. Our data show increased claudin-5 and occludin expression in oxygen and glucose (OGD)-deprived murine brain capillary cerebellar endothelial cells (cerebEND) after STVNa treatment. Likewise, the upregulation of the transmembrane protein integrin-αv was also observed. Finally, cell volume was reduced with the simultaneous administration of STVNA and OGD in cerebEND cells. In neuropathologies such as stroke, the failure of cell volume control is a major feature leading to loss of cells in the penumbra as well as adverse outcomes. Our initial findings, therefore, point to the neuroprotective effects of STVNA at the BBB in vitro, which warrant further investigation for a possible future clinical intervention.},
  language  = {en}
}