脑缺血远隔部位炎性反应的多模式神经影像学活体实验研究

The secondary damage in remote area after focal cerebral ischemia is one of the important causes of poor functional rehabilitation after stroke. The applicant has found that inflammatory reaction plays a significant part in the secondary damage of the remote area post-stroke, and there are differences in the inflammatory responses with the primary ischemic foci in terms of time evolution, spatial distribution, and cell types. But the physiological significance of inflammatory response in the remote area has not yet been clarified. We speculated that inflammatory response in the remote area causes the damage of the neurovascular unit, while promotes the angiogenesis and neurogenesis as well, and have different timing characteristics compared to that of the primary ischemic foci. For confirm this hypothesis, we will apply multiple morphological and functional neuroimaging techniques, especially the manganese-enhanced magnetic resonance imaging, combining neuro-pathological method to study the dynamic process of cerebral ischemia, reflect the changes of neurons, glial cell, blood vessel, tissue perfusion and neural pathway. Thus, it is to reveal the features and role of inflammatory reaction in the remote area, and to justify both similarities and differences with those of the primary ischemic foci. The aim of this project is to image the multiple role of inflammatory reaction after cerebral ischemia in vivo, to establish the secure and efficient means of detecting and evaluating the inflammatory reaction, in order to select proper time window and treat with the more specific intervention for the inflammatory target. It will promote the research process of regarding the inflammatory response as a therapeutic target after cerebral ischemia.

局灶性脑缺血远隔部位发生的继发性损害，是脑卒中后功能康复不良的重要原因之一。本申请者发现，炎性反应参与了脑缺血远隔部位的损害，并证实其与原发缺血灶的炎性反应在时间演变、细胞类型、空间分布等方面存在差异。但是炎性反应的病生理意义尚未阐明。我们推测，脑缺血后远隔部位发生的炎性反应，即具有对神经血管单元的损害作用，同时又具有促进神经发生、血管生成的修复作用，并且与原发缺血灶炎性反应的作用具有不同的时间特征。为证实这一假说，我们应用具有前期基础的多种形态学和功能学神经影像活体技术，特别是锰增强磁共振成像，结合神经病理学方法，反映脑缺血后神经元、胶质细胞、血管、组织灌注和神经连接通路等动态变化，阐明远隔部位炎性反应的特点和作用，比较其与原发病灶的异同，为合理恰当地利用炎性反应的双重作用、选择合适的干预时间窗、进行针对性治疗，提供安全高效的活体检测和评价手段，推动脑缺血炎性反应作为时间靶点的研究进程。

本资助项目充分发挥各种神经影像技术的优势，验证了脑缺血后炎性反应具有广泛性、不均质性和多重效应性，揭示了脑缺血后远隔部位的炎性反应特点，阐明了远隔部位与原发缺血灶炎性反应在发生时间、分布空间、细胞类型、血脑屏障完整性、血流灌注等不同方面存在差异，确立了炎性反应的病生理意义，探明了其与神经发生、神经连接通路损伤和修复、和血管生成的关系，并摸索出一套高效的影像评价手段，在基础研究和临床应用中架起桥梁，为缺血性脑卒中的诊治研究奠定了坚实基础，提供了可靠的检测和评估手段。