低强度聚焦超声深部脑刺激提高γ-氨基丁酸水平的抗癫痫效应及机制研究

超声对癫痫的疗效已被证实，但其机理尚不清楚。抑制性突触输入减少是癫痫发病的重要机制。我们新近发现超声可提高抑制性突触输入，预实验也提示超声刺激使抑制性神经递质γ-氨基丁酸(GABA)水平增加，且可激活GABA能中间神经元和星形胶质细胞并引起各自钙内流增加。据此我们提出科学假说：超声的抗癫痫效应与GABA水平的升高有关，超声一方面可激活中间神经元的机械敏感离子通道，使大量GABA囊泡被释放，另一方面可激活星形胶质细胞的TRPA1通道，引起GABA回收受阻而蓄积。本项目拟研制低强度聚焦超声深部脑刺激装置和离体超声刺激装置，对小鼠癫痫模型进行在体和脑片水平超声刺激，研究GABA水平与超声抗癫痫效应的关系，然后分别验证超声对GABA能中间神经元和星形胶质细胞的激活作用，观察这两类细胞引起GABA水平升高的效应并探讨其机制。本研究将揭示超声的抗癫痫效应及其机制，为超声深部脑刺激技术的应用提供依据。

Ultrasound deep brain stimulation technology has been proven to be effective for epilepsy, but its mechanism remains unclear. Inhibitory synaptic input reduction is an important mechanism of epilepsy. We have recently discovered that ultrasound can increase inhibitory synaptic input, and preliminary experiments have also indicated that ultrasound stimulation increases the level of inhibitory neurotransmitters GABA, and can activate GABAergic interneurons and astrocytes and cause increased calcium influx. According to this, we propose a scientific hypothesis: the antiepileptic effect of ultrasound is mainly related to the increase of GABA levels. On the one hand, ultrasound can activate the mechanically sensitive ion channels of GABAergic interneurons, so that a large number of GABA vesicles are released. On the other hand, it can activate astrocytes. The TRPA1 channel of the cell, which in turn causes GABA recovery to be blocked and accumulates. This project intends to develop low-intensity focused ultrasound deep brain stimulation equipment and in vitro ultrasound stimulation equipment to stimulate the mouse epilepsy model in vivo and brain slice in vitro, to study the relationship between GABA level and ultrasound antiepileptic effect. Verify the ultrasound activation of GABAergic interneurons and astrocytes. Observe the effect of these two types of cells on increasing GABA levels and explore their mechanisms. This study will reveal the antiepileptic effect and mechanism of ultrasound, and provide a basis for the application of ultrasound deep brain stimulation technology.