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

作者：Zhao, Bingxia; Chen, Yihan; Liu, Jinfeng; Zhang, Li; Wang, Jing; Yang, Yali; Lv, Qing; Xie, Mingxing^*

来源：Oncotarget, 2018, 9(4): 4897-4914.

DOI：10.18632/oncotarget.23527

• blood-brain barrier
• diagnostic ultrasound
• microbubble
• drug delivery

Objective: 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. @@@ Results: 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. @@@ Conclusions: 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. @@@ Methods: 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.

• 出版日期2018-1-12
• 单位华中科技大学