Analysis of focused ultrasound with microbubbles induced BBB disruption on tight junction morphology

Focused ultrasound (FUS) with systemically delivered microbubbles has been established to locally, reversibly and non-invasively increase the permeability of the blood brain barrier to facilitate targeted drug delivery to the brain. Despite FUS constituting a promising therapeutic technique, the cellular mechanism of FUS-mediated BBB opening has yet to be fully described. Immunoelectron microscopy of vessels has reported the removal of tight junction (TJ) proteins from the junctional cleft, yet no study has examined the structural integrity of the entire length of the TJ strand following FUS with microbubbles. Furthermore, permeability studies have identified differences in the rate of leakage between large and small vessels, but it remains to be studied if TJ strand morphology differs among vessel types. The aim of the current study is to investigate TJ strand morphology for structural abnormalities in different vessel types following FUS-induced BBB opening.