Aryal, MunaFischer, KrisztinaGentile, CarolineGitto, SalvatoreZhang, Yong-ZhiMcDannold, Nathan2017-02-182017Aryal, Muna, Krisztina Fischer, Caroline Gentile, Salvatore Gitto, Yong-Zhi Zhang, and Nathan McDannold. 2017. “Effects on P-Glycoprotein Expression after Blood-Brain Barrier Disruption Using Focused Ultrasound and Microbubbles.” PLoS ONE 12 (1): e0166061. doi:10.1371/journal.pone.0166061. http://dx.doi.org/10.1371/journal.pone.0166061.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:30371089Many blood-borne substances attempting to pass through the luminal membrane of brain endothelial cells are acted upon by a variety of metabolizing enzymes or are actively expelled back into the capillary lumen by embedded efflux transporters, such as Permeability-glycoprotein (Pgp). Overexpression of this protein has also been linked to multidrug resistance in cancer cells. Previous studies have shown that focused ultrasound (FUS), when combined with a microbubble agent, has ability to temporarily disrupt blood-brain barrier (BBBD). In this work, we investigated whether modulation of Pgp expression is part of the FUS-induced effects. We found that ultrasound can temporarily suppress Pgp expression. When BBBD was produced at 0.55 MPa, Pgp was suppressed up to 48 hours and restored by 72 hours. At 0.81 MPa, suppression can last 72 hours or longer. These findings support the idea that microbubble-enhanced FUS disrupts the functional components of the BBB through suppression of drug efflux.en-USSpecimen Preparation and TreatmentMechanical Treatment of SpecimensSonicationMedicine and Health SciencesDiagnostic MedicineDiagnostic RadiologyMagnetic Resonance ImagingImaging TechniquesRadiology and ImagingPhysical SciencesPhysicsAcousticsPharmaceuticsDrug DeliveryBioacousticsBiology and Life SciencesCell BiologyCellular Structures and OrganellesCell MembranesMembrane ProteinsNeurologyBrain DamageEngineering and TechnologySignal ProcessingSignal FilteringJournal Article2017-02-1810.1371/journal.pone.0166061