Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, 999077, P. R. China.
Adv Sci (Weinh). 2021 Nov;8(21):e2101934. doi: 10.1002/advs.202101934. Epub 2021 Sep 21.
Ultrasound is a promising new modality for non-invasive neuromodulation. Applied transcranially, it can be focused down to the millimeter or centimeter range. The ability to improve the treatment's spatial resolution to a targeted brain region could help to improve its effectiveness, depending upon the application. The present paper details a neurostimulation scheme using gas-filled nanostructures, gas vesicles (GVs), as actuators for improving the efficacy and precision of ultrasound stimuli. Sonicated primary neurons display dose-dependent, repeatable Ca responses, closely synced to stimuli, and increased nuclear expression of the activation marker c-Fos in the presence of GVs. GV-mediated ultrasound triggered rapid and reversible Ca responses in vivo and could selectively evoke neuronal activation in a deep-seated brain region. Further investigation indicate that mechanosensitive ion channels are important mediators of this effect. GVs themselves and the treatment scheme are also found not to induce significant cytotoxicity, apoptosis, or membrane poration in treated cells. Altogether, this study demonstrates a simple and effective method to achieve enhanced and better-targeted neurostimulation with non-invasive low-intensity ultrasound.
超声在非侵入性神经调节中是一种很有前途的新方法。经颅应用时，它可以聚焦到毫米或厘米的范围内。提高治疗的空间分辨率，使其达到靶向脑区的能力，可能会根据应用的不同，从而提高其有效性。本文详细介绍了一种使用充气纳米结构（气穴）作为致动器的神经刺激方案，以提高超声刺激的效果和精度。超声刺激原代神经元后，可观察到剂量依赖性、可重复的 Ca 响应，且与刺激紧密同步，在存在气穴的情况下，激活标志物 c-Fos 的核表达增加。GV 介导的超声在体内可引发快速且可逆的 Ca 响应，并可选择性地在深部脑区诱发电活性神经元激活。进一步的研究表明，机械敏感离子通道是这种效应的重要介导物。还发现气穴本身和治疗方案不会在处理过的细胞中引起明显的细胞毒性、细胞凋亡或膜穿孔。总的来说，这项研究展示了一种简单有效的方法，可通过非侵入性低强度超声实现增强和更靶向的神经刺激。
