Nitro-oleic acid (OA-NO₂), a nitroalkene formed in nitric oxide-dependent oxidative reactions, has been found in human plasma and is thought to regulate pathophysiological functions. Recently, accumulating evidence suggests that OA-NO₂ may function as an anti-inflammatory mediator, and ameliorate the progression of diabetes and cardiovascular diseases. However, the role of OA-NO₂ in ischemic brain injury remains unexplored. In this study, C57BL/6 mice were subjected to 1 h transient middle cerebral artery occlusion (MCAO) and followed by 1– 7 days of reperfusion. These mice were treated with vehicle, OA, or OA-NO₂ (10 mg/kg) via tail vein injection at 2 h after the onset of MCAO. Our results show that intravenous administration of OA-NO₂ led to reduced BBB leakage in ischemic brains, reduced brain infarct, and improved sensorimotor functions in response to ischemic insults when compared to OA and vehicle controls. Also, OA-NO₂ significantly reduced BBB leakage-triggered infiltration of neutrophils and macrophages in the ischemic brains. Moreover, OA-NO₂ treatment reduced the M1-type microglia and increased M2-type microglia. Mechanistically, OA-NO₂ alleviated the decline of mRNA and protein level of major endothelial TJs including ZO-1 in stroke mice. Treatment of OA-NO₂ also significantly inhibited stroke-induced inflammatory mediators, iNOS, E-selectin, P-selectin, and ICAM1, in mouse brains. In conclusion, OA-NO₂ preserves BBB integrity and confers neurovascular protection in ischemic brain damage. OA-NO₂-mediated brain protection may help us to develop a novel therapeutic strategy for the treatment of ischemic stroke.

硝基油酸 (OA-NO ₂ ) 是一种在一氧化氮依赖性氧化反应中形成的硝基烯烃，已在人体血浆中发现并被认为可调节病理生理功能。最近，越来越多的证据表明 OA-NO ₂可能起到抗炎介质的作用，并改善糖尿病和心血管疾病的进展。然而，OA-NO ₂在缺血性脑损伤中的作用仍未探索。在这项研究中，C57BL/6 小鼠接受 1 小时短暂大脑中动脉闭塞 (MCAO)，然后再灌注 1-7 天。用载体、OA 或 OA-NO _{2治疗这些小鼠}(10 mg/kg) 在 MCAO 发作后 2 小时通过尾静脉注射。我们的研究结果表明，与 OA 和载体对照相比，静脉注射 OA-NO ₂可减少缺血性脑中的 BBB 渗漏，减少脑梗死，并改善对缺血性损伤的感觉运动功能。此外，OA-NO ₂显着降低了 BBB 渗漏引发的缺血性脑中中性粒细胞和巨噬细胞的浸润。此外，OA-NO ₂处理减少了 M1 型小胶质细胞并增加了 M2 型小胶质细胞。从机制上讲，OA-NO ₂减轻了中风小鼠主要内皮 TJ 的 mRNA 和蛋白质水平的下降，包括 ZO-1。OA-NO _2的治疗还显着抑制小鼠大脑中中风诱导的炎症介质 iNOS、E-选择素、P-选择素和 ICAM1。总之，OA-NO ₂保持 BBB 完整性并在缺血性脑损伤中提供神经血管保护。OA-NO ₂介导的脑保护可能有助于我们开发一种治疗缺血性中风的新治疗策略。