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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.