Oral Presentations

2007 Cerebrovascular Diseases  
During the last several years great progress has been made in understanding and exploiting the bioeffects of ultrasound, in particular those that occur in conjunction with microbubbles. With the ever expanding diversity of therapeutic ultrasound applications ranging from cell ablation to sonothrombolysis, sonoporation and enhancement of angiogenesis, it is becoming increasingly important to elucidate the molecular mechanisms of ultrasonographic effects in order to provide a sound basis for
more » ... rential usage of this new therapeutic modality. A particularly promising research application with high translational capacity is ultrasound-targeted drug delivery to the brain. As we know, most substances and drugs that would be potentially useful for treatment of a variety of brain disorders cannot be applied due to their inability to penetrate the blood-brain barrier (BBB). This is particularly true for large-molecule agents such as monoclonal antibodies, recombinant proteins, or gene therapeutics. Although a variety of approaches have been investigated to open the BBB for facilitation of drug delivery, none has achieved clinical applicability. Recently, it was shown that ultrasound can facilitate drug delivery across the BBB. Moreover, if microbubbles are introduced to the blood stream prior to ultrasound exposure, the BBB can be opened transiently at the ultrasound focus without neuronal damage. Possible mechanisms for this effect include transcytosis, passage through endothelial cell cytoplasmic openings, opening of tight junctions and free passage through injured endothelium. New developments in drug delivery to the brain exploit this approach with highly innovative microbubbles carrying nanoparticle-loaded agents. In combination with BBB opening, this new targeting strategy will allow non-invasive therapies to the brain with substances such as immunoglobulins, viral vectors, plasmid DNA, siRNA, mRNA and high molecular weight drugs. To accommodate this progress, further research will be required that addresses the effects of ultrasound and microbubbles upon the various transport mechanisms of the BBB. Moreover, investigations aimed at elucidating how ultrasound and microbubbles interact at the molecular level of the BBB will be highly beneficial for guidance of future clinical translation of this promising ultrasound application. TCD assessing chronic ischemia (vasomotor reactivity): clinical significance Bornstein NM, Gur AY
doi:10.1159/000104179 pmid:17708021 fatcat:5eg2g6kklzhmfcyhrnljuhfeze