Blood-brain barrier disruption induced by diagnostic ultrasound combined with microbubbles in mice
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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
Mingxing Xie, email: email@example.com
Keywords: blood-brain barrier; diagnostic ultrasound; microbubble; drug delivery
Received: September 07, 2017 Accepted: December 04, 2017 Published: December 21, 2017
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.
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