缺血脑卒中早期，血脑屏障(BBB)完整性对于减轻脑损伤至关重要。小胶质/巨噬细胞在脑卒中早期即通过参与中枢及外周免疫炎症反应调控BBB完整性，但其对BBB的作用及机制尚不清。我们前期研究发现，脑卒中后早期缺血神经元分泌白介素（IL）-34增加，侧脑室注射IL-34可显著减轻卒中后BBB损伤。由于IL-34是集落刺激因子-1受体（CSF-1R）的天然配体，且预实验发现增强小胶质/巨噬细胞的吞噬功能标记物CD206、CD36和TREM2显著增强，由此提出假说：缺血性脑卒中后，IL-34可作为缺血神经元释放的求救信号，通过小胶质/巨噬细胞表面CSF-1R，增强其吞噬功能，清除BBB损伤后渗漏至脑组织的纤维蛋白Fibrin，减轻神经炎症反应，保护卒中后BBB及神经血管单元。本研究拟应用骨髓移植、共聚焦及细胞培养等技术证明上述假说，为缺血性脑卒中早期BBB免疫保护机制理论支撑和治疗靶点。

The integrity of blood brain barrier(BBB) is extremely important to reduce brain injury in the early stage of ischemic stroke. Microglia/macrophages involved in central and peripheral inflammatory response could regulate the integrity of BBB, but its effect and mechanism on BBB remains unclear. Our previous study found that IL-34 secreted by injured neurons was upregulated in stroke and intracerebroventricular administration of IL-34 could significantly reduce BBB injury by increasing the number of colony stimulating factor-1 receptor (CSF-1R) positive microglia/macrophages, and enhancing the phagocytic function of CSF-1R+ microglia/macrophages as upregulated expression of CD206, CD36 and TREM2. We hypothesized that the central neurons secrete help-me signaling molecules like IL-34 in the early stage of stroke to promote the phagocytic phenotype of microglia/macrophage via IL-34/CSF-1R pathway, clear the fibrin and then protecting BBB and improving neurovascular function. In the present study, we will test the hypothesis by using bone marrow transplantation mouse, confocol microscopic imaging in MCAO model, cell co-culture techniques and other methods. Our studies will provide new target for the research and development of BBB protection in ischemic stroke.