Li Dandan, Yong Yu, Qiao Chaofeng, Jiang Hao, Lin Jiawei, Wei Jianpeng, Zhou Yufeng, Li Fenfang
Institute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen, China.
Institute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen, China; School of Basic Medical Sciences, Beihua University, Jilin City, China.
Ultrasound Med Biol. 2025 Mar;51(3):494-507. doi: 10.1016/j.ultrasmedbio.2024.11.010. Epub 2024 Dec 4.
Low-intensity pulsed ultrasound (LIPUS) is a promising modality for neuromodulation. Microglia are the resident immune cells in the brain and their mobility is critical for maintaining brain homeostasis and alleviating neuroimmune pathologies. However, it is unclear whether and how LIPUS modulates microglial migration in physiological conditions.
Here we examined the in vitro effects of LIPUS on the mobility of BV2 microglia by live cell imaging. Single-cell tracing of BV2 microglia migration was analyzed using ImageJ and Chemotaxis and Migration Tool software. Pharmacological manipulation was performed to determine the key molecular players involved in regulating ultrasound-dependent microglia migration.
We found that the distance of microglial migration was enhanced by LIPUS with increasing acoustic pressure. Removing the extracellular Ca influx or depletion of intracellular Ca stores suppressed ultrasound-enhanced BV2 migration. Furthermore, we found that blocking the reorganization of actin, or suppressing purinergic signaling by application of apyrase or hemi-channel inhibitors, both diminished ultrasound-induced BV2 migration. LIPUS stimulation also enhanced microglial migration in a lipopolysaccharide (LPS)-induced inflammatory environment.
LIPUS promoted microglia migration in both physiological and inflammatory environments. Calcium, cytoskeleton, and purinergic signaling were involved in regulating ultrasound-dependent microglial mobility. Our study reveals the biomechanical impact of ultrasound on microglial migration and highlights the potential of using ultrasound-based tools for modulation of microglial function.
低强度脉冲超声（LIPUS）是一种很有前景的神经调节方式。小胶质细胞是大脑中的常驻免疫细胞，它们的迁移对于维持脑内稳态和减轻神经免疫病变至关重要。然而，尚不清楚LIPUS在生理条件下是否以及如何调节小胶质细胞迁移。
在此，我们通过活细胞成像研究了LIPUS对BV2小胶质细胞迁移能力的体外影响。使用ImageJ以及趋化性和迁移工具软件对BV2小胶质细胞迁移进行单细胞追踪分析。进行药理学操作以确定参与调节超声依赖性小胶质细胞迁移的关键分子。
我们发现，随着声压增加，LIPUS增强了小胶质细胞的迁移距离。去除细胞外钙内流或耗尽细胞内钙储存会抑制超声增强的BV2迁移。此外，我们发现阻断肌动蛋白重组，或通过应用腺苷三磷酸双磷酸酶或半通道抑制剂抑制嘌呤能信号传导，均会减弱超声诱导的BV2迁移。LIPUS刺激在脂多糖（LPS）诱导的炎症环境中也增强了小胶质细胞迁移。
LIPUS在生理和炎症环境中均促进小胶质细胞迁移。钙、细胞骨架和嘌呤能信号传导参与调节超声依赖性小胶质细胞迁移能力。我们的研究揭示了超声对小胶质细胞迁移的生物力学影响，并突出了使用基于超声的工具调节小胶质细胞功能的潜力。
