申请人立足国内，聚焦急性脑血管病(ACD)炎症损伤启动机制，系统研究了ACD神经免疫炎症机制和调控措施。发现HMGB1/TLR4通路启动脑缺血炎症损伤，针对性地阻抑显著降低患者神经损伤。发现TLR4新配体Heme以及TLR2/TLR4新型二聚体，揭示了其启动脑出血炎症损伤的分子机制，获得了二聚体形成的特异抑制剂SsnB。从炎症反应上游环节的角度阐明了ACD神经损伤机制，为临床治疗提供了新思路。获得973课题、NSFC（5项）等资助，以第一/通讯作者在Ann Neurol、J Immunol、Stroke、JCBFM等发表SCI论文21篇，其中IF>10的2篇，被Nat Med、Nat Rev Neurol等杂志他引688次，单篇最高他引182次，为Prog Neurobiol撰写综述，入选重庆市科技创新领军人才。后续研究衰老相关表观遗传学特征在脑出血脑保护中的作用机制，拓展脑保护研究领域。

The applicant has focused on the initial mechanism of inflammatory injury induced by acute cerebral vascular disease (ACD). We systematically studied the mechanism of neuroimmune and the regulation pathways induced by ACD. We found that HMGB1/TLR4 signaling initiated the inflammatory injury induced by cerebral ischemia, and inhibiting the TLR4 signaling could significant reduce the brain injury. We found the Heme was a novel ligand for TLR4 and a novel TLR2/TLR4 heterodimer. Our results also revealed how the heterodimer initial the ICH induced inflammatory injury and got a specific inhibitor which could inhibit the formation of the heterodimers. The results elucidated the initial mechanism of ACD induced inflammatory injury and provided a new target for clinical treatment. We got 973, 5 times NSFC etc funding. As a first and/or corresponding author, I have published 21SCI-indexed papers on the essential journals of this field such as Ann Neurol, stroke, J immunol, JCBFM (two of their IF＞10). These papers have been cited 688 times by journals such as Nat Med, Nat Rev Neurol and etc(highest single article citation of 182). I wrote topic review for Prog Neurobiol and was selected as a scientific innovation first level talented person of Chongqing. We will further investigate the role and mechanism of epigenetic network in brain protection following intracerebral hemorrhage, and extend research field of brain protection.