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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:9

Enthalten in:

Oncotarget - 9(2018), 4 vom: 12. Jan., Seite 4897-4914

Sprache:

Englisch

Beteiligte Personen:

Zhao, Bingxia [VerfasserIn]
Chen, Yihan [VerfasserIn]
Liu, Jinfeng [VerfasserIn]
Zhang, Li [VerfasserIn]
Wang, Jing [VerfasserIn]
Yang, Yali [VerfasserIn]
Lv, Qing [VerfasserIn]
Xie, Mingxing [VerfasserIn]

Links:

Volltext

Themen:

Blood-brain barrier
Diagnostic ultrasound
Drug delivery
Journal Article
Microbubble

Anmerkungen:

Date Revised 14.03.2022

published: Electronic-eCollection

Citation Status PubMed-not-MEDLINE

doi:

10.18632/oncotarget.23527

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM280941587