title: Acute effects of focused ultrasound-induced increases in blood-brain barrier permeability on rat microvascular transcriptome.
abstract: Therapeutic treatment options for central nervous system diseases are greatly limited by the blood-brain barrier (BBB). Focused ultrasound (FUS), in conjunction with circulating microbubbles, can be used to induce a targeted and transient increase in BBB permeability, providing a unique approach for the delivery of drugs from the systemic circulation into the brain. While preclinical research has demonstrated the utility of FUS, there remains a large gap in our knowledge regarding the impact of sonication on BBB gene expression. This work is focused on investigating the transcriptional changes in dorsal hippocampal rat microvessels in the acute stages following sonication. Microarray analysis of microvessels was performed at 6 and 24 hrs post-FUS. Expression changes in individual genes and bioinformatic analysis suggests that FUS may induce a transient inflammatory response in microvessels. Increased transcription of proinflammatory cytokine genes appears to be short-lived, largely returning to baseline by 24 hrs. This observation may help to explain some previously observed bioeffects of FUS and may also be a driving force for the angiogenic processes and reduced drug efflux suggested by this work. While further studies are necessary, these results open up intriguing possibilities for novel FUS applications and suggest possible routes for pharmacologically modifying the technique.
authors.affiliation: University of Toronto, Department of Medical Biophysics, Toronto, M4N 3M5, Canada.|Sunnybrook Research Institute, Toronto, M4N 3M5, Canada.
authors.forename: Dallan
authors.initials: D
authors.lastname: McMahon
authors.affiliation: University of Toronto, Department of Pharmaceutical Sciences, Toronto, M5S 3M2, Canada.
authors.forename: Reina
authors.initials: R
authors.lastname: Bendayan
authors.affiliation: University of Toronto, Department of Medical Biophysics, Toronto, M4N 3M5, Canada.|Sunnybrook Research Institute, Toronto, M4N 3M5, Canada.|University of Toronto, Institute of Biomaterials and Biomedical Engineering, Toronto, M5S 3G9, Canada.
authors.forename: Kullervo
authors.initials: K
authors.lastname: Hynynen
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000528:radiation effects*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply; D008279:Magnetic Resonance Imaging; D008297:Male; D045423:Microbubbles; D055806:Microvessels / Q000378:metabolism / Q000528:radiation effects; D010539:Permeability / Q000528:radiation effects; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome / Q000528:radiation effects*; D000069453:Ultrasonic Waves
chemical_list: D016207:Cytokines