China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
Neurochem Int. 2020 May;135:104690. doi: 10.1016/j.neuint.2020.104690. Epub 2020 Jan 22.
Remote ischemic preconditioning (RIPreC) and postconditioning (RIPostC) have been demonstrated to attenuate brain injury after ischemic stroke in healthy animals. This study investigated whether RIPreC and RIPostC exerted neuroprotection against cerebral ischemic injury in type 2 diabetic mice. RIPreC (24 h before ischemia) and RIPostC (immediately after reperfusion) were performed in an ischemia/reperfusion induced stroke model with type 2 diabetes. Ischemic outcomes, flow cytometry, multiplex cytokine assay, and western blotting were analyzed after 45 min of ischemia followed by 48 h of reperfusion. Our data indicated that RIPreC and RIPostC attenuated cerebral injuries and neurological deficits. RIPreC significantly reduced CD4 T cell and CD8 T cell infiltration and increased B cell infiltration into the ischemic brain. It also upregulated CD4 and CD8 T cell levels in the peripheral blood. However, RIPostC significantly decreased CD8 T cells infiltration and increased B cell infiltration into the ischemic brain. RIPreC inhibited IL-6 level in both the brain and blood, while RIPostC treatment attenuated IL-6 level upregulation in the peripheral blood. In addition, both RIPreC and RIPostC significantly increased p-ERK expression in the ipsilateral hemisphere in diabetic mice. This study indicated that RIPreC and RIPostC neuroprotection is present in type 2 diabetic mice via the modulation of brain ERK activity and inflammatory responses in both the peripheral blood and ischemic brain. However, the benefit was lower in RIPostC.
远程缺血预处理（RIPreC）和后处理（RIPostC）已被证明可减轻健康动物缺血性中风后的脑损伤。本研究旨在探讨 RIPreC 和 RIPostC 是否对 2 型糖尿病小鼠脑缺血损伤具有神经保护作用。在 2 型糖尿病诱导的缺血/再灌注引起的中风模型中进行了 RIPreC（缺血前 24 小时）和 RIPostC（再灌注后即刻）。在缺血 45 分钟后再灌注 48 小时后，分析了缺血结局、流式细胞术、多重细胞因子测定和 Western blot。我们的数据表明，RIPreC 和 RIPostC 减轻了脑损伤和神经功能缺损。RIPreC 显著减少了 CD4 T 细胞和 CD8 T 细胞浸润，并增加了 B 细胞浸润到缺血性大脑。它还上调了外周血中 CD4 和 CD8 T 细胞的水平。然而，RIPostC 显著减少了 CD8 T 细胞浸润，并增加了 B 细胞浸润到缺血性大脑。RIPreC 抑制了大脑和血液中的 IL-6 水平，而 RIPostC 处理减轻了外周血中 IL-6 水平的上调。此外，RIPreC 和 RIPostC 均显著增加了糖尿病小鼠对侧半球中 p-ERK 的表达。本研究表明，RIPreC 和 RIPostC 通过调节外周血和缺血性大脑中的 ERK 活性和炎症反应，为 2 型糖尿病小鼠提供神经保护作用。然而，RIPostC 的益处较低。
