Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei 11221, Taiwan.
Division of Neurosurgery, Cheng Hsin General Hospital, Taipei 11221, Taiwan.
Cereb Cortex. 2020 Jun 30;30(8):4597-4606. doi: 10.1093/cercor/bhaa062.
The purpose of this study was to investigate the effects and underlying mechanisms of low-intensity pulsed ultrasound (LIPUS) against lipopolysaccharide (LPS)-induced neuroinflammation. BV-2 microglia subjected to LPS administration (1 μg/mL) were treated with LIPUS stimulation. The levels of inflammatory mediators and brain-derived neurotrophic factor (BDNF) were quantified using the western blot. The results showed that LIPUS stimulation promoted the associated cAMP response element-binding protein (CREB)/BDNF expression in the LPS-treated microglia. Meanwhile, LIPUS treatment effectively suppressed the LPS-induced production of tumor necrosis factor-α, interleukin-1β, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 in the microglial cells, in addition to inhibiting the LPS-induced expressions of toll-like receptor 4 and myeloid differentiation factor 88, as well as the LPS-induced activation of c-Jun N-terminal kinase and nuclear factor kappa B. Furthermore, LIPUS significantly decreased the Bax/Bcl-2 ratio in the microglia following LPS treatment. Our data indicated that LIPUS attenuated the proinflammatory responses as well as the decline in BDNF in LPS-treated microglia. This study provides a better understanding of how LIPUS stimulation regulates anti-inflammatory actions in microglia, providing further evidence suggesting that such stimulation may be regarded as a novel strategy for the treatment of neuroinflammation.
本研究旨在探讨低强度脉冲超声（LIPUS）对脂多糖（LPS）诱导的神经炎症的作用及其潜在机制。用 LPS（1μg/mL）处理 BV-2 小胶质细胞，然后用 LIPUS 刺激进行处理。使用 Western blot 定量测定炎症介质和脑源性神经营养因子（BDNF）的水平。结果表明，LIPUS 刺激促进了 LPS 处理的小胶质细胞中相关的 cAMP 反应元件结合蛋白（CREB）/BDNF 表达。同时，LIPUS 处理有效抑制了 LPS 诱导的小胶质细胞中肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6、诱导型一氧化氮合酶和环氧化酶-2 的产生，抑制了 LPS 诱导的 Toll 样受体 4 和髓样分化因子 88 的表达，以及 LPS 诱导的 c-Jun N 端激酶和核因子 kappa B 的激活。此外，LIPUS 还显著降低了 LPS 处理后小胶质细胞中 Bax/Bcl-2 比值。我们的数据表明，LIPUS 减弱了 LPS 处理的小胶质细胞中的促炎反应和 BDNF 下降。本研究更好地理解了 LIPUS 刺激如何调节小胶质细胞中的抗炎作用，进一步证明这种刺激可能被视为治疗神经炎症的一种新策略。
