title: Distribution of nanoparticles throughout the cerebral cortex of rodents and non-human primates: Implications for gene and drug therapy.
abstract: When nanoparticles/proteins are infused into the brain, they are often transported to distal sites in a manner that is dependent both on the characteristics of the infusate and the region targeted. We have previously shown that adeno-associated virus (AAV) is disseminated within the brain by perivascular flow and also by axonal transport. Perivascular distribution usually does not depend strongly on the nature of the infusate. Many proteins, neutral liposomes and AAV particles distribute equally well by this route when infused under pressure into various parenchymal locations. In contrast, axonal transport requires receptor-mediated uptake of AAV by neurons and engagement with specific transport mechanisms previously demonstrated for other neurotropic viruses. Cerebrospinal fluid (CSF) represents yet another way in which brain anatomy may be exploited to distribute nanoparticles broadly in the central nervous system. In this study, we assessed the distribution and perivascular transport of nanoparticles of different sizes delivered into the parenchyma of rodents and CSF in non-human primates.
authors.affiliation: Department of Neurological Surgery, University of California at San Francisco San Francisco, CA, USA.
authors.forename: Ernesto A
authors.initials: EA
authors.lastname: Salegio
authors.affiliation: Department of Neurological Surgery, University of California at San Francisco San Francisco, CA, USA.
authors.forename: Hillary
authors.initials: H
authors.lastname: Streeter
authors.affiliation: Department of Materials Science & Engineering, University of California at Berkeley Berkeley, CA, USA.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Dube
authors.affiliation: Department of Neurological Surgery, University of California at San Francisco San Francisco, CA, USA.
authors.forename: Piotr
authors.initials: P
authors.lastname: Hadaczek
authors.affiliation: Department of Neurological Surgery, University of California at San Francisco San Francisco, CA, USA.
authors.forename: Lluis
authors.initials: L
authors.lastname: Samaranch
authors.affiliation: Department of Neurological Surgery, University of California at San Francisco San Francisco, CA, USA.
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Kells
authors.affiliation: Department of Neurological Surgery, University of California at San Francisco San Francisco, CA, USA.
authors.forename: Waldy
authors.initials: W
authors.lastname: San Sebastian
authors.affiliation: Department of Neurological Surgery, University of California at San Francisco San Francisco, CA, USA.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Department of Neurological Surgery, University of California at San Francisco San Francisco, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Bringas
authors.affiliation: Department of Materials Science & Engineering, University of California at Berkeley Berkeley, CA, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Neurological Surgery, University of California at San Francisco San Francisco, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Forsayeth
authors.affiliation: Department of Neurological Surgery, University of California at San Francisco San Francisco, CA, USA.
authors.forename: Krystof S
authors.initials: KS
authors.lastname: Bankiewicz
keywords: AAV; CSF; gene delivery; liposomes; perivascular; thalamo-cortico