EV71具有嗜神经性，能引起致死性中枢神经系统（CNS）并发症。血脑屏障（Blood-Brain Barrier, BBB）是维持CNS内环境稳定的重要结构。EV71感染引起的CNS并发症与BBB损伤有关，但BBB损伤的机制尚未明确。研究表明，补体C5a/C5aR通路介导的炎症反应可能参与BBB损伤。我们前期研究发现，EV71感染小鼠脑组织补体C5a升高、小胶质细胞C5aR活化，这表明C5a/C5aR通路活化。本研究采用hSCARB2+/+C5aR1-/-小鼠和C5aR阻断剂干预探讨C5a/C5aR通路是否参与EV71感染后BBB损伤；通过构建体外BBB模型结合体内外细胞信号转导研究策略，进一步揭示C5a/C5aR通路调控小胶质细胞TNF-α表达促进BBB损伤的分子机制。本研究有助于揭示EV71感染致BBB损伤的机制，为EV71感染重症患者的治疗提供潜在干预靶点。

Enterovirus 71 (EV71) is neurotrophic and can cause fatal central nervous system (CNS) complications. The homeostasis of CNS is maintained by blood-brain barrier (BBB). CNS complications caused by EV71 infection is likely due to the disruption of BBB, but how EV71 causes BBB damage after EV71 is not yet clear. It has been reported that C5a, a complement (C) split product of C5, and its receptor (C5aR)-mediated inflammation is involved in BBB damage. Indeed, our previous study showed an increase of C5a in EV71-infected mice brains and C5aR activation in microglia, implying the activation of C5a/C5aR pathway. In this study, we will use hSCARB2+/+C5aR1-/- mice and a C5aR-specific inhibitor to explore whether the C5a/C5aR pathway contributes to BBB damage after EV71 infection. We will further investigate which signaling pathways activated in microglia through the C5aR induce TNF-α expression to promote BBB damage after EV71 infection in vitro and in vivo. This study will be helpful to reveal the mechanism of BBB damage caused by EV71 infection and provide a potential target for therapeutic intervention of severe patients with EV71 infection.