title: Effects on P-Glycoprotein Expression after Blood-Brain Barrier Disruption Using Focused Ultrasound and Microbubbles.
abstract: Many 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.
authors.affiliation: Department of Radiology, Brigham & Women's Hospital, Harvard Medical School, Boston, United States of America.
authors.forename: Muna
authors.initials: M
authors.lastname: Aryal
authors.affiliation: Department of Radiology, Brigham & Women's Hospital, Harvard Medical School, Boston, United States of America.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Fischer
authors.affiliation: Department of Radiology, Brigham & Women's Hospital, Harvard Medical School, Boston, United States of America.|Department of Neurobiology, Harvard College, Cambridge, United States of America.
authors.forename: Caroline
authors.initials: C
authors.lastname: Gentile
authors.affiliation: Department of Radiology, University of Pavia, Pavia, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Gitto
authors.affiliation: Department of Radiology, Brigham & Women's Hospital, Harvard Medical School, Boston, United States of America.
authors.forename: Yong-Zhi
authors.initials: YZ
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Brigham & Women's Hospital, Harvard Medical School, Boston, United States of America.
authors.forename: Nathan
authors.initials: N
authors.lastname: McDannold
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D002199:Capillary Permeability; D002560:Cerebrovascular Circulation; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D045423:Microbubbles; D051381:Rats; D017207:Rats, Sprague-Dawley; D013010:Sonication; D013997:Time Factors; D014465:Ultrasonics
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C095122:multidrug resistance protein 3