Ischemic stroke is one of the leading causes of death and disability worldwide. The severe sequelae caused by ischemic thrombolysis and the narrow time window are now the main clinical challenges. Our previous study has reported 4-Trifluoromethyl-(E)-cinnamoyl]-L-4-F-phenylalanine Acid (AE-18) was a promising candidate for Parkinson’s Disease. In this study, the preventive and therapeutic effects of AE-18 on focal cerebral ischemia-reperfusion injury and the mechanisms are explored. In oxygen glucose deprivation/reoxygenation (OGD/R)-induced well-differentiated PC12 cells model, AE-18 (10 or 20 μM) can significantly reduce nerve damage when administered before or after molding. In middle cerebral artery occlusion-reperfusion (MCAO/R) rat model, pre-modelling, or post-modelling administration of AE-18 (5 or 10 mg/kg) was effective in reducing neurological damage, decreasing infarct volume and improving motor disturbances. In addition, AE-18 (5 mg/kg) given by intravenous injection immediately after occlusion significantly reduce the infarct volume caused by reperfusion for different durations, indicating that AE-18 could extend the time window of thrombolytic therapy. Further studies demonstrate that AE-18 exerts the effects in the prevention, treatment, and prolongation of the time window of cerebral ischemic injury mainly through inhibiting excitotoxicity and improving BBB permeability, VEGF and BDNF. These results suggest that AE-18 is a good candidate for the treatment of ischemic stroke.

缺血性中风是全世界死亡和残疾的主要原因之一。缺血性溶栓引起的严重后遗症和狭窄的时间窗是目前临床的主要挑战。我们之前的研究报道了 4-三氟甲基-( E )-肉桂酰基] -L -4-F-苯丙氨酸 ( AE-18 ) 是帕金森病的有希望的候选者。本研究探讨AE-18对局灶性脑缺血再灌注损伤的预防和治疗作用及其机制。在氧葡萄糖剥夺/复氧 (OGD/R) 诱导的高分化 PC12 细胞模型中，AE-18（10 或 20 μM）在成型前或成型后给药可显着减少神经损伤。在大脑中动脉闭塞-再灌注 (MCAO/R) 大鼠模型中，建模前或建模后施用AE-18（5 或 10 mg/kg）可有效减少神经损伤、减少梗塞体积和改善运动障碍. 此外，闭塞后立即静脉注射AE-18 （5 mg/kg）可显着减少不同持续时间再灌注引起的梗死体积，表明AE-18可以延长溶栓治疗的时间窗。进一步的研究表明，AE-18主要通过抑制兴奋性毒性，改善血脑屏障通透性、VEGF和BDNF，发挥预防、治疗和延长脑缺血损伤时间窗的作用。这些结果表明AE-18是治疗缺血性中风的良好候选者。