Abstract
Focused ultrasound (FUS) with microbubbles opens the blood-brain barrier (BBB) to allow targeted drug delivery into the brain; however, the mechanisms of BBB opening and the response of the neurovascular unit at either low acoustic pressures, known to open the BBB transiently, or high pressures that cause brain damage, remain unclear. Employing a transgenic mouse strain where tight junctions (TJs) are labelled with eGFP, we examined TJ strand morphology at 1 and 72 hours post-FUS at both low and high pressures. We find that transient BBB opening due to FUS is not caused by TJ strand damage, unless FUS is used at high pressures, and this is localized primarily in arterioles and capillaries. At high pressures, TJ strands are obliterated and remain unrepaired even at 72 hours, allowing for fibrinogen passage, and persistent microglial activation. Our findings suggest that at low safe pressures, upregulation of transcytosis may likely increase transiently BBB permeability to deliver therapeutics to the brain.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
