title: Influence of nanoparticles on blood-brain barrier permeability and brain edema formation in rats.
abstract: Nanoparticles are small sized (1-100 nm) particles derived from transition metals, silver, copper, aluminum, silicon, carbon and metal oxides that can easily cross the blood-brain barrier (BBB) and/or produce damage to the barrier integrity by altering endothelial cell membrane permeability. However, the influence of nanoparticles on BBB integrity is still not well-known. In this investigation, effect of nanoparticles derived from Ag, Al and Cu (50-60 nm) on BBB permeability in relation to brain edema formation was examined in a rat model. Intravenous (30 mg/kg), intraperitoneal (50 mg/kg) or intracerebral (20 microg in 10 microL) administration of Ag, Cu or Al nanoparticles disrupted the BBB function to Evans blue albumin (EBA) and radioiodine in rats 24 h after administration and induced brain edema formation. The leakage of Evans blue dye was observed largely in the ventral surface of brain and in the proximal frontal cortex. The dorsal surfaces of cerebellum showed mild to moderate EBA staining. These effects were most pronounced in animals that received Ag or Cu nanoparticles compared to Al nanoparticles through intravenous routes. These observations are the first to suggest that nanoparticles can induce brain edema formation by influencing BBB breakdown in vivo.
authors.affiliation: Laboratory of Cerebrovascular Research, Department of Surgical Science, Anesthesiology and Intensive Care Medicine, University Hospital, Uppsala, Sweden. Sharma@surgsci.uu.se
authors.forename: Hari Shanker
authors.initials: HS
authors.lastname: Sharma
authors.forename: Saber
authors.initials: S
authors.lastname: Hussain
authors.forename: John
authors.initials: J
authors.lastname: Schlager
authors.forename: Syed F
authors.initials: SF
authors.lastname: Ali
authors.forename: Aruna
authors.initials: A
authors.lastname: Sharma
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001929:Brain Edema / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D005070:Evans Blue; D008670:Metals / Q000633:toxicity; D053758:Nanoparticles / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008670:Metals; D005070:Evans Blue