title: Temporal assessment of nanoparticle accumulation after experimental brain injury: Effect of particle size.
abstract: Nanoparticle (NP) based therapeutic and theranostic agents have been developed for various diseases, yet application to neural disease/injury is restricted by the blood-brain-barrier (BBB). Traumatic brain injury (TBI) results in a host of pathological alterations, including transient breakdown of the BBB, thus opening a window for NP delivery to the injured brain tissue. This study focused on investigating the spatiotemporal accumulation of different sized NPs after TBI. Specifically, animal cohorts sustaining a controlled cortical impact injury received an intravenous injection of PEGylated NP cocktail (20, 40, 100, and 500 nm, each with a unique fluorophore) immediately (0 h), 2 h, 5 h, 12 h, or 23 h after injury. NPs were allowed to circulate for 1 h before perfusion and brain harvest. Confocal microscopy demonstrated peak NP accumulation within the injury penumbra 1 h post-injury. An inverse relationship was found between NP size and their continued accumulation within the penumbra. NP accumulation preferentially occurred in the primary motor and somatosensory areas of the injury penumbra as compared to the parietal association and visual area. Thus, we characterized the accumulation of particles up to 500 nm at different times acutely after injury, indicating the potential of NP-based TBI theranostics in the acute period after injury.
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, USA.
authors.forename: Vimala N
authors.initials: VN
authors.lastname: Bharadwaj
authors.affiliation: Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA.|Department of Child Health, University of Arizona, College of Medicine-Phoenix, Phoenix, AZ, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lifshitz
authors.affiliation: Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA.|Department of Child Health, University of Arizona, College of Medicine-Phoenix, Phoenix, AZ, USA.
authors.forename: P David
authors.initials: PD
authors.lastname: Adelson
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, USA.
authors.forename: Vikram D
authors.initials: VD
authors.lastname: Kodibagkar
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Stabenfeldt
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D006735:Horseradish Peroxidase / Q000378:metabolism; D057446:Hydrodynamics; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D055672:Static Electricity; D013997:Time Factors
chemical_list: D006735:Horseradish Peroxidase