Effect of anesthetics on microglial activation and nanoparticle uptake: Implications for drug delivery in traumatic brain injury.
J Control Release
; 263: 192-199, 2017 Oct 10.
Article
em En
| MEDLINE
| ID: mdl-28336376
ABSTRACT
Traumatic brain injury (TBI) is a serious public health problem, often with devastating consequences for patients and their families. Affordable and timely therapies can have a substantial impact on outcomes in severe TBI. Despite the common use of sedatives and anesthetics in the acute phase of TBI management, their effect on glial cells is not well understood. We investigated the effect of a commonly used sedative, pentobarbital, on glial cells and their uptake of nanoparticles. First, we studied how pentobarbital affects BV2 mouse microglial cells in culture. The cell morphology was imaged by confocal microscopy and analyzed. Our results suggest that microglia change to a more swollen, 'activated' shape with pentobarbital (cell area increased by approximately 20%, p<0.001). Such glial activation may have negative implications for the ability of the injured brain to clear edema. Second, we investigated how pentobarbital treatment affected nanoparticle uptake. BV-2 mouse microglial cells in the presence and absence of pentobarbital were treated with fluorescently-labeled, hydroxyl-functionalized poly(amidoamine) dendrimer nanoparticles (Dendrimer-Cy5). We demonstrated that the presence of pentobarbital increased the dendrimer nanoparticle uptake significantly (~2-fold both 2 and 6h following treatment). This semi-quantitative fluorescence assessment was broadly consistent among confocal image analysis, flow cytometry, and fluorescence quantification of cell-extracted dendrimer-Cy5. Although anesthetics appear to activate microglia, the increased uptake of dendrimer nanoparticles in their presence can be exploited to deliver drug-loaded nanoparticles directly to microglia after TBI. These drugs could restore glial and glymphatic function, enabling efficient drainage of waste and fluid from the brain and effectively improving recovery after TBI. A key future direction is to validate these findings in TBI models.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pentobarbital
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Microglia
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Dendrímeros
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Anestésicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Control Release
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos