The Key Laboratory of Biomedical Information Engineering of the Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
Xijing Hospital, Traditional Chinese Medicine, Xi'an 710032, China.
Ultrason Sonochem. 2019 Dec;59:104745. doi: 10.1016/j.ultsonch.2019.104745. Epub 2019 Aug 23.
Microbubbles (MBs) are known to serve as an amplifier of the mechanical effects of ultrasound, which combined with ultrasound are widely used in brain. The goal of this study is to investigate the effect of oscillating MBs on the neuronal activity in the central nervous system (CNS) of mammals. The motor cortex of mice brain was subjected to ultrasound stimulation with and without MBs, and evoked electromyogram signals were recorded. A c-fos immunofluorescence assay was performed to evaluate the neuronal activation in the region of ultrasound stimulation. BBB integrity during ultrasound stimulation with MBs was assessed in this study. Moreover, the safety of ultrasound stimulation with MBs was examined. Using ultrasound at 620 kHz, the injection of MBs significantly increased the success rate of motor response from 0.065 ± 0.06 to 0.28 ± 0.10 when stimulation was applied at 0.12 MPa and from 0.38 ± 0.09 to 0.77 ± 0.18 at 0.25 MPa (p < 0.001). The results of the c-fos immunofluorescence assay showed that the mean densities of c-fos cells were significantly increased from 15.67 ± 3.51 to 53.01 ± 9.54 at 0.12 MPa acoustic pressure. At 0.25 MPa, the mean density of c-fos + cells was 81 ± 10.97 without MBs and it significantly increased to 124.12 ± 25.71 with MBs (p < 0.05). Enhanced neuronal activities were observed with 0.12 MPa ultrasound stimulation with MBs, while the integrity of BBB was not compromised, but 0.25 MPa ultrasound stimulation with MBs resulted in BBB disruption. These findings reveal that the oscillations of MBs can enhance neuronal activity in the CNS of mammals, and may provide an insight into the application of MBs combined with ultrasound in brain.
微泡（MBs）已知可作为超声机械效应的放大器，与超声结合广泛用于脑。本研究的目的是研究振荡 MBs 对哺乳动物中枢神经系统（CNS）神经元活动的影响。用和不用 MBs 对小鼠脑运动皮层进行超声刺激，并记录诱发的肌电图信号。进行 c-fos 免疫荧光测定以评估超声刺激区域的神经元激活。在本研究中评估了超声刺激期间 BBB 的完整性。此外，还检查了 MBs 与超声联合使用的安全性。使用 620 kHz 的超声，当在 0.12 MPa 时刺激时，MBs 的注射将运动反应的成功率从 0.065 ± 0.06 显著提高到 0.28 ± 0.10，而当在 0.25 MPa 时从 0.38 ± 0.09 提高到 0.77 ± 0.18（p < 0.001）。c-fos 免疫荧光测定的结果表明，在 0.12 MPa 声压下，c-fos 细胞的平均密度从 15.67 ± 3.51 显著增加到 53.01 ± 9.54。在 0.25 MPa 时，没有 MBs 的 c-fos + 细胞的平均密度为 81 ± 10.97，而有 MBs 时显著增加到 124.12 ± 25.71（p < 0.05）。用 MBs 增强的 0.12 MPa 超声刺激观察到增强的神经元活动，而 BBB 的完整性没有受到损害，但用 MBs 的 0.25 MPa 超声刺激导致 BBB 破坏。这些发现表明，MBs 的振荡可以增强哺乳动物 CNS 中的神经元活动，并可能为 MBs 与超声联合应用于大脑提供新的见解。
