低强度经颅超声治疗创伤性脑损伤及其机制研究

Traumatic brain injury (TBI) with the characteristics of high incidence and disability has become a major public health problem. The TBI study focused mainly on neuron-synaptic concerns but little was reported on extracellular space (ECS), extracellular matrix (ECM), interstitial fluid (ISF) and interstitial space (ISS). Previous studies have shown that low-intensity transcranial ultrasound (LIPUS) therapy with the advantages of non-invasive, high spatial resolution and high penetration depth could prompt patients to be awake, however the related mechanism is not yet clear. We combine the above-mentioned latest developments with our previous foundations to propose the new research ideas. This project uses TBI rats as the research object, focuses on whether TBI affects the ECS-ECM structure and the ISF function of ISS system, and explores whether LIPUS can promote the key issues of TBI brain rehabilitation to fusion. We combine magnetic resonance imaging and LIPUS technology and use Gd-DTPA magnetic tracer method and MRI-based multimodal analysis method to improve the scientific parameters of low-intensity transcranial ultrasound and explore related therapy mechanisms of TBI. Furthermore, we optimize the key parameters of LIPUS therapy for TBI to improve the best therapeutic rehabilitation effect. This study has theoretical significance and potential medical value.

创伤性脑损伤(TBI)具有高发生率和致残率，已成为重大的社会公共卫生问题。TBI研究主要关注于神经元-突触，对细胞外间隙（ECS）、细胞外基质（ECM）、脑组织通道（ISS）、脑组织间液（ISF）报道甚少。研究表明，具有无创、高空间分辨和高穿透深度优点的低强度经颅超声（LIPUS）治疗能够促使患者清醒，但机制尚不清。我们综合国内外最新进展及我们的前期基础，提出新的研究构想。本项目以TBI大鼠为研究对象，紧紧围绕TBI是否影响ECS-ECM结构及ISS体系的ISF功能，探索LIPUS治疗能否促进TBI脑康复的关键问题，融合核磁成像技术与LIPUS治疗技术，使用Gd-DTPA磁示踪法及MRI为主的多模态分析方法，完善低强度经颅超声的科学参数，探索TBI最适宜的LIPUS治疗康复疗法及机制。进一步优化LIPUS对TBI治疗的关键参数，获得最佳的治疗康复效果。此研究具有理论意义和潜在的医疗价值。

本项目通过低强度经颅超声刺激（Low intensity transcranial ultrasound stimulation, LITUS）对TBI中度损伤的大鼠进行试验性治疗，并通过各种不同方式进行疗效评价，主要包括：（1）利用磁共振成像的弥散加权成像序列中的ADC值、DKI序列、各向同性三维T2序列、T2加权序列等，对中度TBI大鼠的损伤及恢复情况进行定量评估，多维度、多角度评估了LITUS对TBI大鼠脑的保护作用，证实了LITUS对于TBI的确切疗效；同时，证实了这些序列对于TBI评估的价值；（2）通过对实验动物行为学以及实验动物脑组织病理学、生化分析，发现LITUS治疗TBI的机制可能与提高神经功能、改善突触可塑性、减轻脑水肿有着密切关系。（3）通过LITUS诱导的小鼠视皮层钙振荡和BOM、钙振荡与BOM的时域耦合、闭环经颅超声刺激使LITUS对TBI的治疗作用达到最佳效果,研究治疗TBI的最适宜参数，为临床TBI的治疗提供一种新的思路。本项目共发表SCI论文10篇。国家发明专利一篇。