TY - JOUR
T1 - Temporal assessment of nanoparticle accumulation after experimental brain injury
T2 - Effect of particle size
AU - Bharadwaj, Vimala N.
AU - Lifshitz, Jonathan
AU - Adelson, P. David
AU - Kodibagkar, Vikram
AU - Stabenfeldt, Sarah
N1 - Funding Information:
This study was supported by the FLINN Foundation (S.E.S., V.D.K., J.L., P.D.A.) and NIH (1DP2HD084067; SES).
PY - 2016/7/22
Y1 - 2016/7/22
N2 - 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.
AB - 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.
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U2 - 10.1038/srep29988
DO - 10.1038/srep29988
M3 - Article
C2 - 27444615
AN - SCOPUS:84979256576
SN - 2045-2322
VL - 6
JO - Scientific reports
JF - Scientific reports
M1 - 29988
ER -