Ultrasound, microbubbles and the blood–brain barrier

Abstract

The blood-brain barrier (BBB) is a specialized system of capillary endothelial cells that protects the brain from harmful substances in the blood stream, while supplying the brain with the required nutrients for proper function. The BBB controls transport through both tight junctions and metabolic barriers and is often a rate-limiting factor in determining permeation of therapeutic drugs into the brain. It is a significant obstacle for delivery of both small molecules and macromolecular agents. Although many drugs could be potentially used to treat brain disease, there has been no method that allows non-invasive-targeted delivery through the BBB. Recently, promising studies indicate that ultrasound can be used to locally deliver a drug or gene to a specific region of interest in the brain. If microbubbles are combined with ultrasound exposure, the effects of ultrasound can be focused upon the vasculature to reduce the acoustic intensity needed to produce BBB opening. Several avenues of transcapillary passage after ultrasound sonication have been identified including transcytosis, passage through endothelial cell cytoplasmic openings, opening of tight junctions and free passage through injured endothelium. This article reviews the topic of transient disruption of the BBB with ultrasound and microbubbles and addresses related safety issues. It also discusses possible roles of the BBB in brain disease and potential interactions with ultrasound and microbubbles in such disease states.

Perfluorocarbons: Life sciences and biomedical uses Dedicated to the memory of Professor Guy Ourisson, a true RENAISSANCE man.

“…52 Such combinations may also enable noninvasive brain surgery, 53 as well as targeted drug delivery via transient opening of the blood-brain barrier. 54 PFC-based microbubbles are not the only PFC products useful in diagnosis. 42 Neat F-octyl bromide gained FDA approval for oral use as a bowel marker during MRI of the gastrointestinal tract.…”

Primary Porcine Brain Endothelial Cells as In Vitro Model to Study Effects of Ultrasound and Microbubbles on Blood–Brain Barrier Function

“…A number of studies have been dedicated to obtain more knowledge on the effects of ultrasound (US) and microbubbles on BBB permeability [10], [11], and to understand the mechanisms by which US and microbubbles enhance transcytosis or open tight junctions [12]. Cavitation, i.e.…”

"SonoBandage" a transdermal ultrasound drug delivery system for peripheral neuropathy

“…Recently, high intensity focused ultrasound (HIFU) has been shown as an effective tool to target systemic drug treatments (Coussios et al, 2007;Frenkel, 2008). Ultrasound mediated disruption of the blood brain barrier is being studied to help drugs escape the blood stream and enter the brain (Hynynen et al, 2003;Hynynen, 2007;Hynynen and Clement, 2007;Meairs and Alonso, 2007;Yang et al, 2008). US has also been shown to enhance the transport of molecules in agarose, muscle and brain tissue in vitro and in vivo Lewis Jr., 2010a;.…”