title: Effects of copper nanoparticles on rat cerebral microvessel endothelial cells.
abstract: OBJECTIVE
  The purpose of the current study was to determine whether copper nanoparticles (Cu-NPs) can induce the release of proinflammatory mediators that influence the restrictive characteristics of the blood-brain barrier.
  
  
  METHODS
  Confluent rat brain microvessel endothelial cells (rBMECs) were treated with well-characterized Cu-NPs (40 or 60 nm). Cytotoxicity of the Cu-NPs was evaluated by cell proliferation assay (1.5-50 µg/ml). The extracellular concentrations of proinflammatory mediators (IL-1β, IL-2, TNF-α and prostaglandin E(2)) were evaluated by ELISA.
  
  
  RESULTS
  The exposure of Cu-NPs at low concentrations increases cellular proliferation of rBMECs, by contrast, high concentrations induce toxicity. Prostaglandin E(2) release was significantly increased (threefold; 8 h) for Cu-NPs (40 and 60 nm). The extracellular levels of both TNF-α and IL-1β were significantly elevated following exposure to Cu-NPs. The P-apparent ratio, as an indicator of increased permeability of rBMEC was approximately twofold for Cu-NPs (40 and 60 nm).
  
  
  CONCLUSIONS
  These data suggest that Cu-NPs can induce rBMEC, proliferation at low concentrations and/or induce blood-brain barrier toxicity and potential neurotoxicity at high concentrations.
authors.affiliation: Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR 72079, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Trickler
authors.forename: Susan M
authors.initials: SM
authors.lastname: Lantz
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Schrand
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Robinson
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Newport
authors.forename: John J
authors.initials: JJ
authors.lastname: Schlager
authors.forename: Merle G
authors.initials: MG
authors.lastname: Paule
authors.forename: William
authors.initials: W
authors.lastname: Slikker
authors.forename: Alexandru S
authors.initials: AS
authors.lastname: Biris
authors.forename: Saber M
authors.initials: SM
authors.lastname: Hussain
authors.forename: Syed F
authors.initials: SF
authors.lastname: Ali
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003300:Copper / Q000737:chemistry / Q000276:immunology* / Q000633:toxicity; D015232:Dinoprostone / Q000276:immunology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D053583:Interleukin-1beta; D007376:Interleukin-2; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C052994:interleukin-1beta (163-171); D003300:Copper; D015232:Dinoprostone