Department of Anesthesiology, National Taiwan University College of Medicine and National University Hospital, Taipei, Taiwan.
Graduate Institutes of Anatomy and Cell Biology, National Taiwan University College of Medicine, 1 Jen-Ai Road, Section 1, Taipei, 100233, Taiwan.
Mol Neurobiol. 2022 Nov;59(11):7045-7055. doi: 10.1007/s12035-022-03020-0. Epub 2022 Sep 8.
Adenosine, lidocaine, and magnesium (ALM) are clinically available cardioplegic solutions. We examined the effects of low-dose ALM on ischemic stroke in cell and animal models. Cobalt chloride (CoCl)-treated SH-SY5Y cells were used as a surrogate model to mimic oxygen-glucose deprivation conditions. The cells were incubated with different dilutions of ALM authentic solution (1.0 mM adenosine, 2.0 mM lidocaine, and5 mM MgSO4 in Earle's balanced salt solution). At a concentration of 2.5%, ALM significantly reduced CoCl-induced cell loss. This protective effect persisted even when ALM was administered 1 h after the insult. We used transient middle cerebral artery occlusion to investigate the therapeutic effects of ALM in vivo. Rats were randomly assigned to two groups-the experimental (ALM) and control (saline) groups-and infusion was administered during the ischemia for 1 h. The infarction area was significantly reduced in the ALM group compared with the control group (5.0% ± 2.0% vs. 23.5% ± 5.5%, p = 0.013). Neurological deficits were reduced in the ALM group compared with the control group (modified Longa score: 0 [0-1] vs. 2 [1-2], p = 0.047). This neuroprotective effect was substantiated by a reduction in the levels of various neuronal injury markers in plasma. These results demonstrate the neuroprotective effects of ALM and may provide a new therapeutic strategy for ischemic stroke.
腺苷、利多卡因和镁(ALM)是临床上可用的心脏停搏液。我们在细胞和动物模型中研究了低剂量 ALM 对缺血性中风的影响。氯化钴(CoCl)处理的 SH-SY5Y 细胞被用作模拟缺氧-葡萄糖剥夺条件的替代模型。将细胞用不同稀释度的 ALM 真实溶液(Earle 平衡盐溶液中的 1.0 mM 腺苷、2.0 mM 利多卡因和 5 mM MgSO4)孵育。在 2.5%的浓度下,ALM 显著减少了 CoCl 诱导的细胞丢失。即使在损伤后 1 小时给予 ALM,这种保护作用仍然存在。我们使用短暂性大脑中动脉闭塞来研究 ALM 在体内的治疗效果。大鼠随机分为两组-实验组(ALM)和对照组(盐水)-并在缺血期间进行 1 小时的输注。与对照组相比,ALM 组的梗死面积明显减小(5.0%±2.0% vs. 23.5%±5.5%,p=0.013)。与对照组相比,ALM 组的神经功能缺损减少(改良 Longa 评分:0[0-1] vs. 2[1-2],p=0.047)。血浆中各种神经元损伤标志物水平的降低证实了这种神经保护作用。这些结果表明了 ALM 的神经保护作用,并可能为缺血性中风提供一种新的治疗策略。