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首页> 外文期刊>Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism >A probable dual mode of action for both L- and D-lactate neuroprotection in cerebral ischemia
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A probable dual mode of action for both L- and D-lactate neuroprotection in cerebral ischemia

机译：L-和D-乳酸神经保护作用在脑缺血中可能的双重作用模式。

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摘要

Lactate has been shown to offer neuroprotection in several pathologic conditions. This beneficial effect has been attributed to its use as an alternative energy substrate. However, recent description of the expression of the HCA1 receptor for lactate in the central nervous system calls for reassessment of the mechanism by which lactate exerts its neuroprotective effects. Here, we show that HCA1 receptor expression is enhanced 24 hours after reperfusion in an middle cerebral artery occlusion stroke model, in the ischemic cortex. Interestingly, intravenous injection of L-lactate at reperfusion led to further enhancement of HCA1 receptor expression in the cortex and striatum. Using an in vitro oxygen-glucose deprivation model, we show that the HCA1 receptor agonist 3,5-dihydroxybenzoic acid reduces cell death. We also observed that D-lactate, a reputedly non-metabolizable substrate but partial HCA1 receptor agonist, also provided neuroprotection in both in vitro and in vivo ischemia models. Quite unexpectedly, we show D-lactate to be partly extracted and oxidized by the rodent brain. Finally, pyruvate offered neuroprotection in vitro whereas acetate was ineffective. Our data suggest that L-and D-lactate offer neuroprotection in ischemia most likely by acting as both an HCA1 receptor agonist for non-astrocytic (most likely neuronal) cells as well as an energy substrate.
机译：乳酸已显示出在几种病理状态下均能提供神经保护作用。该有益效果归因于其用作替代性能量底物。但是，最近关于乳酸盐的HCA1受体在中枢神经系统中表达的描述要求重新评估乳酸盐发挥其神经保护作用的机制。在这里，我们显示缺血大脑皮层中脑动脉闭塞性中风模型再灌注后24小时，HCA1受体表达增强。有趣的是，在再灌注时静脉内注射L-乳酸导致皮质和纹状体中HCA1受体的表达进一步增强。使用体外氧-葡萄糖剥夺模型，我们显示HCA1受体激动剂3,5-二羟基苯甲酸减少细胞死亡。我们还观察到，D-乳酸盐（一种据说不可代谢的底物，但部分HCA1受体激动剂）在体外和体内缺血模型中也提供了神经保护作用。出乎意料的是，我们显示D-乳酸被啮齿动物的大脑部分提取和氧化。最后，丙酮酸在体外提供神经保护作用，而乙酸盐则无效。我们的数据表明，L-乳酸和D-乳酸在神经缺血中最可能通过充当非星形细胞（最可能是神经元）细胞的HCA1受体激动剂以及能量底物来提供神经保护。

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