Narayanan Srinivasan V, Perez-Pinzon Miguel A
Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, Miami, Florida, USA.
Neuroscience Program, University of Miami Miller School of Medicine, Miami, Florida, USA.
Cond Med. 2017 Dec;1(1):2-8.
Ischemic preconditioning (IPC) represents a potential therapy against cerebral ischemia. While our group has previously shown IPC to induce neuroprotection through various pathways, the role of astrocytes in supporting IPC-induced neuroprotection has not been extensively studied. Astrocyte-derived lactate has gained attention as a potential soluble mediator through which astrocytes could impart ischemic tolerance to neurons. Therefore, the goal of this study was to determine if i) IPC-treatment of astrocytes alone could transfer ischemic tolerance to neurons; ii) if IPC-treatment of astrocytes increases lactate production; and if iii) exogenous lactate administration to neurons could induce neuroprotection against lethal ischemia in vitro. For this purpose, a co-culture system was used and modified from a previous method. This system allows astrocytes and neurons to be separated by a physical barrier, while allowing secreted substances from either cell type to interact with each other. Oxygen-glucose deprivation was used as a model of cerebral ischemia and IPC in cultured rodent astrocytes and neurons. Neurons incubated with IPC-treated astrocytes were significantly protected against lethal ischemic injury compared to neurons incubated with sham-treated astrocytes. In addition, IPC-treatment of astrocytes significantly increased lactate secretion into the extracellular media. Finally, exogenous lactate administration can significantly attenuate cell death in neuronal cultures following exposure to lethal OGD. Our results suggest that IPC-treatment of astrocytes alone can transfer ischemic tolerance to neurons. In addition, the ability of IPC to increase lactate production in astrocytes suggest that lactate could represent a neuroprotective agent to protect neurons against lethal ischemic injury.
缺血预处理（IPC）是一种针对脑缺血的潜在治疗方法。虽然我们的研究小组之前已表明IPC可通过多种途径诱导神经保护作用，但星形胶质细胞在支持IPC诱导的神经保护中的作用尚未得到广泛研究。星形胶质细胞衍生的乳酸作为一种潜在的可溶性介质受到关注，星形胶质细胞可通过它赋予神经元缺血耐受性。因此，本研究的目的是确定：i）单独对星形胶质细胞进行IPC处理是否能将缺血耐受性传递给神经元；ii）对星形胶质细胞进行IPC处理是否会增加乳酸生成；以及iii）向神经元外源性给予乳酸是否能在体外诱导针对致死性缺血的神经保护作用。为此，使用了一种共培养系统，并对先前的方法进行了改进。该系统允许星形胶质细胞和神经元被物理屏障分隔开，同时允许任何一种细胞类型分泌的物质相互作用。氧糖剥夺被用作培养的啮齿动物星形胶质细胞和神经元中脑缺血和IPC的模型。与用假处理的星形胶质细胞孵育的神经元相比，与用IPC处理的星形胶质细胞孵育的神经元对致死性缺血损伤有显著的保护作用。此外，对星形胶质细胞进行IPC处理可显著增加细胞外培养基中的乳酸分泌。最后，外源性给予乳酸可显著减轻暴露于致死性氧糖剥夺后的神经元培养物中的细胞死亡。我们的结果表明，单独对星形胶质细胞进行IPC处理可将缺血耐受性传递给神经元。此外，IPC增加星形胶质细胞中乳酸生成的能力表明，乳酸可能是一种神经保护剂，可保护神经元免受致死性缺血损伤。
