Blood-brainbarrier disruption dictates nanoparticle accumulation following experimental brain injury.
Nanomedicine
; 14(7): 2155-2166, 2018 10.
Article
in En
| MEDLINE
| ID: mdl-29933022
ABSTRACT
Clinically, traumatic brain injury (TBI) results in complex heterogeneous pathology that cannot be recapitulated in single pre-clinical animal model. Therefore, we focused on evaluating utility of nanoparticle (NP)-based therapeutics following three diffuse-TBI models mildclosed-head injury (mCHI), repetitive-mCHI and midline-fluid percussion injury (FPI). We hypothesized that NP accumulation after diffuse TBI correlates directly with blood-brainbarrier permeability. Mice received PEGylated-NP cocktail (20-500 nm) (intravenously) after single- or repetitive-(1 impact/day, 5 consecutive days) CHI (immediately) and midline-FPI (1 h, 3 h and 6 h). NPs circulated for 1 h before perfusion/brain extraction. NP accumulation was analyzed using fluorescent microscopy in brain regions vulnerable to neuropathology. Minimal/no NP accumulation after mCHI/RmCHI was observed. In contrast, midlineFPI resulted in significant peak accumulation of up to 500 nm NP at 3 h post-injury compared to sham, 1 h, and 6 h groups in the cortex. Therefore, our study provides the groundwork for feasibility of NP-delivery based on NPinjection time and NPsize after mCHI/RmCHI and midline-FPI.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain Injuries
/
Blood-Brain Barrier
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Cell Membrane Permeability
/
Disease Models, Animal
/
Nanoparticles
Limits:
Animals
Language:
En
Journal:
Nanomedicine
Journal subject:
BIOTECNOLOGIA
Year:
2018
Document type:
Article
Affiliation country:
Azerbaijan