2020-06-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/711789摘要：目前醫療界已開始注意到超音波對神經調節的作用，並開始嘗試用於腦部疾病的治療。但是對於超音波的生物物理機轉還不是很清楚，也因此限制了超音波的應用。為了瞭解超音波刺激如何影響細胞的分子機轉，我們研發了一套可精確控制的微能量超音波(VLIUS)系統，該系統的優點是可排除超音波的熱效應或空蝕效應。經由這套系統，我們發現了VLIUS的確可以影響細胞-細胞間與細胞-基質間的黏著，並可激發細胞骨架中有關黏著的分子開關。因此，我們將嘗試使用這套設備來刺激腦細胞與鼠腦，評估VLIUS是否可以用來治療腦血管疾病。總計畫將與工業界合作開發VLIUS設備以便提供給所有的子計畫使用，並與法國腦科學跨學科研究所(Interdisciplinary Institute for Neuroscience, IINS)展開跨國合作。子計畫一將觀察VLIUS對腦部內多種細胞的機械傳導反應，子計畫二則觀察VLIUS刺激下的神經軸突生長與突觸成形，子計畫三則研究VLIUS刺激對人工3D中樞神經組織之影響，這三項子計畫將釐清VLIUS刺激對腦細胞影響的生物理論基礎。同時，我們亦分別以動物模型探討VLIUS刺激對缺血性中風(子計畫四)和血管性失智(子計畫五)是否有正面影響。藉由檢驗VLIUS對細胞、組織和動物層級的影響，我們希望研發出一使用超音波治療缺血性中風和血管性失智方法。<br> Abstract: Ultrasound neuromodulation has received increasing attention from medical community as a potential therapeutic treatment for brain diseases. However, a clear understanding of the biophysical processes in action with ultrasonic treatments remain lacking. This limits the application of ultrasound in brain stimulation. To help answer how cells react to ultrasound stimulation and which molecular machinery is involved in these responses, we have developed a very low intensity ultrasound (VLIUS) device to investigate biological mechanisms in cells activated by ultrasound. The advantage of VLIUS is to exclude invasive effects, such as heat and cavitation, during stimulation. With VLIUS, we have established that ultrasound influences cell adhesion (both cell/substrate and cell/cell) and promotes the engagement of molecular clutches linking the adhesion complex to actin networks. In this project, we propose to extend the application of VLIUS devices for stimulation of brain cells/tissues and mouse brain. The main project will be working with industrial partners to develop suitable VLIUS devices and collaborate with IINS in France to incorporate VLIUS in their super resolution imaging facility. Subproject 1 will investigate the responses of brain cells to VLIUS stimulation while Subproject 2 will look into the effect of VLIUS on axonal outgrowth and synapse formation. Subproject 3 will explore the effect of VLIUS on CNS tissues. The results from these three subproject will form the biological basis for VLIUS effect on brain cells and tissues. These findings will be used to formulate a therapeutic protocol for brain disease treatment. We focus on two popular brain diseases in this project: ischemic stroke in subproject 4 and vascular dementia in subproject 5. Equipped with the understanding of brain cellular reactions to VLIUS, subprojects 4 & 5 explore the possibility of using VLIUS as a treatment protocol for brain diseases in animal models. Combining the results of all 5 subprojects, we aim to illuminate the underlining biological mechanisms for brain cellular responses to VLIUS and demonstrate the potential of VLIUS as a therapeutic treatment for brain cerebrovascular diseases.微能量超音波(VLIUS)腦血管疾病腦細胞機械傳導人工三維中樞神經組織動物模型缺血性中風血管性失智Very low intensity ultrasound (VLIUS)cerebrovascular diseasebrain cellmechanotransductionengineered 3D CNS tissueanimal modelischemic strokevascular dementia,