Natural Aging Increases Focused Ultrasound-Induced Blood-Brain Barrier Opening in Wild-Type Mice

Focused Ultrasound (FUS) paired with systemically-introduced microbubbles (MB) is a widely-used noninvasive technique for transiently opening the Blood-Brain Barrier (BBB). FUS-BBBO is implicated in the treatment of several age-associated neuropathological disorders. The prevalence of these diseases in aged populations necessitates an investigation into and an understanding of the effect of age on the brain's response to FUS-BBBO. Here we show that advanced natural aging increases the brain's susceptibility to FUS-BBBO by increasing the volume of BBBO in response to equivalent sonication parameters. Additionally, the BBBO volume correlates positively with cavitation dose (CD). However, the extent of BBBO in response to cavitation is greater in two- compared to one-year old mice. Taken together, these results indicate an increased sensitivity in aged compared to younger mice, highlighting an important consideration in therapeutic planning.