Conclusions
These results suggest that DEX provides a means of modulating the duration of BBB permeability enhancement and may reduce the risk of inflammation-induced tissue damage, increasing the safety profile of this drug-delivery strategy. This effect may be especially relevant in scenarios for which the goal of treatment is to restore or preserve neural function and multiple sonications are required.
Methods
A single-element focused transducer (transmit frequency = 580 kHz) and DefinityTM microbubbles were used to increase BBB permeability unilaterally in the dorsal hippocampi of adult male rats. Sonicating pressure was calibrated based on ultraharmonic emissions. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to quantitatively assess BBB permeability at 15 min (baseline) and 2 hrs following sonication. DEX was administered following baseline imaging and at 24 hrs post-FUS+MB exposure. Expression of key inflammatory proteins were assessed at 2 days, and astrocyte activation and blood vessel growth were assessed at 10 days post-FUS+MB exposure.
Results
Compared to saline-treated control animals, DEX administration expedited the restoration of BBB integrity at 2 hrs, and significantly limited the production of key inflammation-related proteins at 2 days, following sonication. Indications of FUS+MB-induced astrocyte activation and vascular growth were diminished at 10 days in DEX-treated animals, compared to controls. Conclusions: These results suggest that DEX provides a means of modulating the duration of BBB permeability enhancement and may reduce the risk of inflammation-induced tissue damage, increasing the safety profile of this drug-delivery strategy. This effect may be especially relevant in scenarios for which the goal of treatment is to restore or preserve neural function and multiple sonications are required.