The present study was designed to determine the effect of different doses of oxytocin (OXT) on neuronal injury, spatial memory, blood-brain barrier (BBB) integrity and to explore possible underlying molecular mechanisms in the early stage of stroke in mice. Stroke model was generated by middle cerebral artery occlusion (MCAO) for 60 min and 24 h reperfusion in mice. OXT at doses of 1, 2, 4 and 8 IU/per mouse was administrated intranasally at the beginning of brain ischemia. Brain injury, BBB integrity, and spatial memory were evaluated by standard methods. Changes in the expression of nuclear factor-kappa B (NF-κB), and TUNEL positive cell were detected by immunohistochemistry. The levels of vascular endothelial growth factor (VEGF), aquaporin-4 (AQP4) and brain-derived neurotrophic factor (BDNF) proteins were determined by western blotting and ELISA methods. OXT at doses of 4 and 8 IU/per mouse reduced the infarct size by 42% and 52%, respectively, and improved spatial memory function (p < 0.001). OXT (8 IU/per mouse) significantly reduced brain edema, BBB disruption and upregulated the AQP4 expression (p < 0.001). Finally, OXT significantly diminished the number of apoptotic, NF-κB positive cells and enhanced the expression of BDNF and VEGF proteins in the brain tissue (p < 0.001). These findings provide important evidences that OXT significantly suppresses neuronal damage in the early stage of stroke by inhibiting apoptotic and NF-κB signaling pathway, increasing the expression of VEGF, AQP4 and BDNF proteins and reducing the BBB leakage.

本研究旨在确定不同剂量的催产素 (OXT) 对神经元损伤、空间记忆、血脑屏障 (BBB) 完整性的影响，并探讨小鼠中风早期可能的潜在分子机制。中风模型是通过大脑中动脉闭塞 (MCAO) 60 分钟和 24 小时再灌注小鼠产生的。在脑缺血开始时鼻内施用 1、2、4 和 8 IU/每只小鼠的 OXT。通过标准方法评估脑损伤、血脑屏障完整性和空间记忆。免疫组化检测核因子κB（NF-κB）和TUNEL阳性细胞表达的变化。血管内皮生长因子（VEGF）的水平，通过蛋白质印迹和ELISA方法测定水通道蛋白4（AQP4）和脑源性神经营养因子（BDNF）蛋白。每只小鼠 4 和 8 IU 剂量的 OXT 分别使梗塞面积减少了 42% 和 52%，并改善了空间记忆功能。p  < 0.001)。OXT（8 IU/每只小鼠）显着减少脑水肿、BBB 破坏并上调 AQP4 表达（p  < 0.001）。最后，OXT 显着减少了凋亡、NF-κB 阳性细胞的数量，并增强了脑组织中 BDNF 和 VEGF 蛋白的表达（p  < 0.001）。这些发现为OXT通过抑制细胞凋亡和NF-κB信号通路，增加VEGF、AQP4和BDNF蛋白的表达，减少BBB渗漏，显着抑制卒中早期神经元损伤提供了重要证据。