Understanding the mechanisms of ultrasound-targeted microbubble cavitation-mediated blood brain barrier opening

Ultrasound-targeted microbubble cavitation (UTMC) transiently opens the blood brain barrier (BBB). We previously determined that UTMC induces BBB hyperpermeability through an influx of calcium. As activation of RhoA is a calcium-dependent pathway that causes cytoskeletal reorganization, leading to t...

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Bibliographic Details
Published in:The Journal of the Acoustical Society of America 2023-03, Vol.153 (3_supplement), p.A99-A99
Main Authors: Conway, Grace E., Paranjape, Anurag N., Chen, Xucai, Villanueva, Flordeliza S.
Format: Article
Language:English
Online Access:Get full text
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Summary:Ultrasound-targeted microbubble cavitation (UTMC) transiently opens the blood brain barrier (BBB). We previously determined that UTMC induces BBB hyperpermeability through an influx of calcium. As activation of RhoA is a calcium-dependent pathway that causes cytoskeletal reorganization, leading to the breakdown of tight junctions, we tested the hypothesis that UTMC-induced activation of RhoA leads to BBB hyperpermeability. We utilized a transwell model with brain endothelial cells and astrocytes on opposite sides of a support membrane. Ultrasound (1 MHz, 250 kPa, 10 μs pulse duration, 10 ms pulse interval) was applied in the presence of lipid microbubbles for 20 s. BBB permeability was assessed using dextran flux and transendothelial electrical resistance (TEER) measured across the membrane. Integrity of tight junctions was evaluated by staining for ZO-1. UTMC reduced TEER (p 
ISSN:0001-4966
1520-8524
DOI:10.1121/10.0018297