title: Focused Ultrasound-Induced Neurogenesis Requires an Increase in Blood-Brain Barrier Permeability.
abstract: 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.
authors.affiliation: Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Skyler J
authors.initials: SJ
authors.lastname: Mooney
authors.affiliation: Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Kairavi
authors.initials: K
authors.lastname: Shah
authors.affiliation: Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Sharon
authors.initials: S
authors.lastname: Yeung
authors.affiliation: Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Alison
authors.initials: A
authors.lastname: Burgess
authors.affiliation: Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Aubert
authors.affiliation: Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Kullervo
authors.initials: K
authors.lastname: Hynynen
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000528:radiation effects*; D002199:Capillary Permeability; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D045423:Microbubbles; D055495:Neurogenesis; D000069453:Ultrasonic Waves