Microbubble formulation influences inflammatory response to focused ultrasound exposure in the brain

Focused ultrasound and microbubble (FUS + MB)-mediated blood-brain barrier (BBB) permeability enhancement can facilitate targeted brain-drug delivery. This work investigated the relationship between BBB permeability enhancement and the relative transcription of inflammatory mediators 4 h following sonication using three microbubble formulations (Definity, BG8774, and MSB4). While changes in proinflammatory mediator transcription correlated with BBB permeability enhancement, these correlations depended on microbubble formulation; MSB4 (monodisperse, 4 µm diameter) showed significantly greater slopes in regression analyses compared to Definity or BG8774 (polydisperse, <2 µm diameter). An acoustic feedback control algorithm effectively limited emissions and red blood cell extravasation, but microbubble formulation still influenced BBB leakage and acoustic emission correlations. The study demonstrates that while initial BBB permeability enhancement influences inflammatory responses, microbubble characteristics also play a significant role.

Dallan McMahon, Anne Lassus, Emmanuel Gaud, Victor Jeannot, Kullervo Hynynen