Ultrasounds induce blood–brain barrier opening across a sonolucent polyolefin plate in an in vitro isolated brain preparation

Fondazione IRCCS Istituto Neurologico Carlo Besta researchers teamwork, in collaboration with INRiM, demonstrates in the study “Ultrasounds induce blood–brain barrier opening across a sonolucent polyolefin plate in an in vitro isolated brain preparation”, published in Scientific Reports, that US-treated brains displayed blood–brain barrier (BBB) permeabilization exclusively in the volume under the US beam.

The blood–brain barrier (BBB) represents a major obstacle to the drugs delivery in the central nervous system. The combined use of low-intensity pulsed ultrasound waves and intravascular microbubbles (MB) represents a promising solution to this issue, allowing reversible disruption of the barrier. 

In this study, researchers evaluate the feasibility of BBB opening through a biocompatible, polyolefin-based plate in an in vitro whole brain model. Twelve in vitro guinea pig brains were employed; brains were insonated using INRiM made planar transducer with or without interposing the polyolefin plate during arterial infusion of MB. Circulating MBs were visualized with an ultrasonographic device. BBB permeabilization was assessed by quantifying at confocal microscopy the extravasation of FITC-albumin perfused after each treatment. US-treated brains displayed BBB permeabilization exclusively in the volume under the US beam; no significant differences were observed between brains insonated with or without the polyolefin plate. 

Control brains not perfused with MB did not show signs of FITC-albumin extravasation.  Our preclinical study suggests that polyolefin cranial plate could be implanted as a skull replacement to maintain craniotomic windows and perform post-surgical repeated BBB opening with ultrasound guidance to deliver therapeutic agents to the central nervous system.