title: Microglia Determine Brain Region-Specific Neurotoxic Responses to Chemically Functionalized Carbon Nanotubes.
abstract: Surface tunability and their ability to translocate plasma membranes make chemically functionalized carbon nanotubes (f-CNTs) promising intracellular delivery systems for therapeutic or diagnostic purposes in the central nervous system (CNS). The present study aimed to determine the biological impact of different types of multiwalled CNTs (MWNTs) on primary neuronal and glial cell populations isolated from fetal rat frontal cortex (FCO) and striatum (ST). Neurons from both brain regions were generally not affected by exposure to MWNTs as determined by a modified LDH assay. In contrast, the viability of mixed glia was reduced in ST-derived mixed glial cultures, but not in FCO-derived ones. Cytotoxicity was independent of MWNT type or dose, suggesting an inherent sensitivity to CNTs. Characterization of the cell populations in mixed glial cultures prior to nanotube exposure showed higher number of CD11b/c positive cells in the ST-derived mixed glial cultures. After exposure to MWNTs, CNT were uptaken more effectively by CD11b/c positive cells (microglia), compared to GFAP positive cells (astrocytes). When exposed to conditioned media from microglia enriched cultures exposed to MWNTs, ST-derived glial cultures secreted more NO than FCO-derived cells. These results suggested that the more significant cytotoxic response obtained from ST-derived mixed glia cultures was related to the higher number of microglial cells in this brain region. Our findings emphasize the role that resident macrophages of the CNS play in response to nanomaterials and the need to thoroughly investigate the brain region-specific effects toward designing implantable devices or delivery systems to the CNS.
authors.affiliation: Nanomedicine Lab, Faculty of Medical & Human Sciences & National Graphene Institute, University of Manchester , AV Hill Building, Manchester M13 9PT, United Kingdom.|Faculty of Life Sciences, University College London , Brunswick Square, London WC1N 1AX, United Kingdom.
authors.forename: Cyrill
authors.initials: C
authors.lastname: Bussy
authors.affiliation: Faculty of Life Sciences, University College London , Brunswick Square, London WC1N 1AX, United Kingdom.
authors.forename: Khuloud T
authors.initials: KT
authors.lastname: Al-Jamal
authors.affiliation: INSERM U955, Institut Mondor de Recherche Biomédicale , Créteil F-94010 , France.|Université Paris Est Val de Marne (UPEC) , Créteil F-94010, France.|AP-HP, Hôpital Henri Mondor, Service de Physiologie Explorations Fonctionnelles , Créteil F-94010, France.
authors.forename: Jorge
authors.initials: J
authors.lastname: Boczkowski
authors.affiliation: INSERM U955, Institut Mondor de Recherche Biomédicale , Créteil F-94010 , France.|Université Paris Est Val de Marne (UPEC) , Créteil F-94010, France.|Hôpital Intercommunal de Créteil , Service de Pneumologie et Pathologie Professionnelle, Créteil F-94000, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lanone
authors.affiliation: Center of Excellence for Nanostructured Materials, Department of Pharmaceutical Sciences, University of Trieste , Trieste 34127, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Prato
authors.affiliation: CNRS, Institut de Biologie Moléculaire et Cellulaire , UPR 3572, Immunopathologie et Chimie Thérapeutiques, 67000 Strasbourg, France.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bianco
authors.affiliation: Nanomedicine Lab, Faculty of Medical & Human Sciences & National Graphene Institute, University of Manchester , AV Hill Building, Manchester M13 9PT, United Kingdom.|Faculty of Life Sciences, University College London , Brunswick Square, London WC1N 1AX, United Kingdom.
authors.forename: Kostas
authors.initials: K
authors.lastname: Kostarelos
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001923:Brain Chemistry; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016503:Drug Delivery Systems; D005333:Fetus; D005625:Frontal Lobe / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism; D009928:Organ Specificity; D061251:Primary Cell Culture; D051381:Rats
chemical_list: D015415:Biomarkers; D039481:CD11b Antigen; D039521:CD11c Antigen; D017077:Culture Media, Conditioned; D005904:Glial Fibrillary Acidic Protein; D037742:Nanotubes, Carbon; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase
keywords: brain; carbon nanotubes; implant; nanomaterials; nanotoxicology