Oncotarget

Research Papers:

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

Bingxia Zhao, Yihan Chen, Jinfeng Liu, Li Zhang, Jing Wang, Yali Yang, Qing Lv and Mingxing Xie _

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2018; 9:4897-4914. https://doi.org/10.18632/oncotarget.23527

Metrics: PDF 2071 views  |   HTML 2597 views  |   ?  


Abstract

Bingxia Zhao1,2,*, Yihan Chen1,2,*, Jinfeng Liu1,2, Li Zhang1,2, Jing Wang1,2, Yali Yang1,2, Qing Lv1,2 and Mingxing Xie1,2

1Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

2Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

*These authors contributed equally to this work

Correspondence to:

Mingxing Xie, email: xiemx@hust.edu.cn

Keywords: blood-brain barrier; diagnostic ultrasound; microbubble; drug delivery

Received: September 07, 2017     Accepted: December 04, 2017     Published: December 21, 2017

ABSTRACT

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 23527