Focused Ultrasound-Induced Neurogenesis Requires an Increase in Blood-Brain Barrier Permeability.

Author: Mooney SJ1, Shah K1, Yeung S1, Burgess A1, Aubert I2,3, Hynynen K1,4
Affiliation: <sup>1</sup>Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada. <sup>2</sup>Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada. <sup>3</sup>Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. <sup>4</sup>Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Conference/Journal: PLoS One.
Date published: 2016 Jul 26
Other: Volume ID: 11 , Issue ID: 7 , Pages: e0159892 , Special Notes: doi: 10.1371/journal.pone.0159892. eCollection 2016. , Word Count: 155


Transcranial focused ultrasound technology used to transiently open the blood-brain barrier, is capable of stimulating hippocampal neurogenesis; however, it is not yet known what aspects of the treatment are necessary for enhanced neurogenesis to occur. The present study set out to determine whether the opening of blood-brain barrier, the specific pressure amplitudes of focused ultrasound, and/or the intravenous administration of microbubbles (phospholipid microspheres) are necessary for the enhancement of neurogenesis. Specifically, mice were exposed to burst (10ms, 1Hz burst repetition frequency) focused ultrasound at the frequency of 1.68MHz and with 0.39, 0.78, 1.56 and 3.0MPa pressure amplitudes. These treatments were also conducted with or without microbubbles, at 0.39 + 0.78MPa or 1.56 + 3.0MPa, respectively. Only focused ultrasound at the ~0.78 MPa pressure amplitude with microbubbles promoted hippocampal neurogenesis and was associated with an increase in blood-brain barrier permeability. These results suggest that focused ultrasound -mediated neurogenesis is dependent upon the opening of the blood-brain barrier.

PMID: 27459643 PMCID: PMC4961388 DOI: 10.1371/journal.pone.0159892