Ischemic stroke initiated by transient or permanent cerebral blood flow decline remains the leading cause of permanent disability in industrialized nations. Therapeutic strategies to improve patient recovery are remain limited. Hypoxia post-conditioning (HPostC) has been known to be neuroprotective against ischemic injuries in vivo and in vitro. Understanding its mechanism of action may promote its clinical translation. In this study, we devised a method of HPostC treatment to provide protection from a focal cerebral ischemic induced injury and to explore the underling mechanism. We found that our HPostC method improved energy supply by elevating the level of glucose, pyruvate and ATP/ADP ratio within the cerebral hemisphere in mice. In the distal middle cerebral artery occlusion (dMCAO) mice, this HPostC treatment reduced infarct size, and was associated with increased levels of pyruvate, pyruvate/lactate ratio and ATP/ADP ratio. Western blot analysis indicated that the HPostC treatment up-regulated AMPK signaling activities in the cerebral hemisphere. Our results suggest that this HPostC treatment exerts its neuroprotective effect by promoting glycolysis to elevate the ATP/ADP level, and the AMPK/PFKFB3 signaling pathway. These findings may provide biomarkers for clinical use of HPostC methods.

由短暂或永久性脑血流量下降引发的缺血性中风仍然是工业化国家永久性残疾的主要原因。改善患者康复的治疗策略仍然有限。已知缺氧后处理 (HPostC)在体内和体外对缺血性损伤具有神经保护作用. 了解其作用机制可能会促进其临床转化。在这项研究中，我们设计了一种 HPostC 治疗方法，以防止局灶性脑缺血引起的损伤并探索其潜在机制。我们发现我们的 HPostC 方法通过提高小鼠大脑半球内葡萄糖、丙酮酸和 ATP/ADP 的水平来改善能量供应。在远端大脑中动脉闭塞 (dMCAO) 小鼠中，这种 HPostC 治疗减少了梗塞面积，并与丙酮酸、丙酮酸/乳酸比和 ATP/ADP 比的水平增加有关。蛋白质印迹分析表明，HPostC 处理上调了大脑半球的 AMPK 信号活动。我们的结果表明，这种 HPostC 治疗通过促进糖酵解来提高 ATP/ADP 水平来发挥其神经保护作用，和 AMPK/PFKFB3 信号通路。这些发现可能为 HPostC 方法的临床应用提供生物标志物。