Microbubble-enhanced ultrasonic neuromodulation of motor cortex of mouse

This study investigated the effect of MB oscillations on neuronal activity in the central nervous system (CNS) of mammals. The motor cortex of mouse was subjected to ultrasound (US) stimulation with and without MBs. Electromyogram (EMG) signals were recorded by tungsten electrodes. An immunofluorescence assay with antibodies against c-fos was performed to examine the evoked neuronal activity. The influence of US stimulation with MBs on blood brain barrier (BBB) integrity was also assessed. The presence of MBs significantly increased the success rate of motor response from 6.5% ± 6% to 28% ± 10% at 0.12 MPa acoustic pressure. At 0.25 MPa, the success rate was 38% ± 9% without MBs and it significantly increased to 77% ± 18% with MBs. Compared to the US stimulation alone group, the density of c-fos⁺ cells in the region of stimulation was significantly increased for US+MBs group, which indicated that MBs oscillations would enhance neuronal activity. The examination of BBB integrity showed that 0.12 MPa US stimulation with MBs did not result in disruption of BBB integrity while MB oscillations still produced enhanced effect on ultrasonic neuromodulation, suggesting that the neuromodulatory effects induced by MBs is independent on BBB opening. These findings advance the understanding of the effects of MB oscillation on neuronal activity, and break new avenues for the application of MBs in brain.