Blood-brain barrier disruption induced by diagnostic ultrasound combined with microbubbles in mice

• DOI: 10.18632/oncotarget.23527
• Publication Date: 2017-12-21T12:21:25Z
• Authors: Bingxia Zhao; Yihan Chen; Jinfeng Liu; Li Zhang; Jing Wang; Yali Yang; Qing Lv; Mingxing Xie
• Keywords: 0301 basic medicine; 03 medical and health sciences; Research Paper; 3. Good health

To investigate the effects of the microbubble (MB) dose, mechanism index (MI) and sonication duration on blood-brain barrier (BBB) disruption induced by diagnostic ultrasound combined with MBs as well as to investigate the potential molecular mechanism.The extent of BBB disruption increased with MB dose, MI and sonication duration. A relatively larger extent of BBB disruption associated with minimal tissue damage was achieved by an appropriate MB dose and ultrasound exposure parameters with diagnostic ultrasound. Decreased expression of ZO-1, occludin and claudin-5 were correlated with disruption of the BBB, as confirmed by paracellular passage of the tracer lanthanum nitrate into the brain parenchyma after BBB disruption.These findings indicated that this technique is a promising tool for promoting brain delivery of diagnostic and therapeutic agents in the diagnosis and treatment of brain diseases.The extent of BBB disruption was qualitatively assessed by Evans blue (EB) staining and quantitatively analyzed by an EB extravasation measurement. A histological examination was performed to evaluate tissue damage. Expression of tight junction (TJ) related proteins ZO-1, occludin and claudin-5 was determined by western blotting analysis and immunohistofluorescence. Transmission electron microscopy was performed to observe ultrastructure changes of TJs after BBB disruption.