title: Reduced graphene oxide induces transient blood-brain barrier opening: an in vivo study.
abstract: BACKGROUND
  The blood-brain barrier (BBB) is a complex physical and functional barrier protecting the central nervous system from physical and chemical insults. Nevertheless, it also constitutes a barrier against therapeutics for treating neurological disorders. In this context, nanomaterial-based therapy provides a potential alternative for overcoming this problem. Graphene family has attracted significant interest in nanomedicine because their unique physicochemical properties make them amenable to applications in drug/gene delivery and neural interface.
  
  
  RESULTS
  In this study, reduced graphene oxide (rGO) systemically-injected was found mainly located in the thalamus and hippocampus of rats. The entry of rGO involved a transitory decrease in the BBB paracellular tightness, as demonstrated at anatomical (Evans blue dye infusion), subcellular (transmission electron microscopy) and molecular (junctional protein expression) levels. Additionally, we examined the usefulness of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) as a new imaging method for detecting the temporal distribution of nanomaterials throughout the brain.
  
  
  CONCLUSIONS
  rGO was able to be detected and monitored in the brain over time provided by a novel application for MALDI-MSI and could be a useful tool for treating a variety of brain disorders that are normally unresponsive to conventional treatment because of BBB impermeability.
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil. monique.cpm@gmail.com.|Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil. monique.cpm@gmail.com.
authors.forename: Monique Culturato Padilha
authors.initials: MC
authors.lastname: Mendonça
authors.affiliation: Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil. esiqueirasoares@gmail.com.
authors.forename: Edilene Siqueira
authors.initials: ES
authors.lastname: Soares
authors.affiliation: Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil. dejesusmb@gmail.com.
authors.forename: Marcelo Bispo
authors.initials: MB
authors.lastname: de Jesus
authors.affiliation: Department of Semiconductors, Instruments and Photonics, Faculty of Electrical and Computer Engineering, State University of Campinas, Campinas, SP, Brazil. helderjc@gmail.com.
authors.forename: Helder José
authors.initials: HJ
authors.lastname: Ceragioli
authors.affiliation: Department of Medicine and Experimental Surgery, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil. monicasiq@gmail.com.
authors.forename: Mônica Siqueira
authors.initials: MS
authors.lastname: Ferreira
authors.affiliation: Department of Medicine and Experimental Surgery, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil. rrc@fcm.unicamp.br.
authors.forename: Rodrigo Ramos
authors.initials: RR
authors.lastname: Catharino
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil. hofling@unicamp.br.|Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil. hofling@unicamp.br.
authors.forename: Maria Alice
authors.initials: MA
authors.lastname: da Cruz-Höfling
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015153:Blotting, Western; D002196:Capillaries / Q000648:ultrastructure; D006108:Graphite / Q000494:pharmacology*; D006624:Hippocampus / Q000648:ultrastructure; D008297:Male; D018613:Microscopy, Confocal; D008954:Models, Biological; D010084:Oxidation-Reduction; D010087:Oxides / Q000494:pharmacology*; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013056:Spectrophotometry, Ultraviolet; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D010087:Oxides; D006108:Graphite