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

PLoS One

Isabelle Aubert¹  Kullervo Hynynen²  Kairavi Shah³  Sharon Yeung³  Skyler J. Mooney³  Alison Burgess³ 

[1] Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada;Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada

关键词: Hippocampal neurogenesis;    Dentate gyrus;    Neurogenesis;    Neurons;    Mouse models;    Blood-brain barrier;    Sound pressure;    Magnetic resonance imaging;   

DOI  :  10.1371/journal.pone.0159892

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY