Ischemic preconditioning treatment of astrocytes transfers ischemic tolerance to neurons.
Ischemic preconditioning treatment of astrocytes transfers ischemic tolerance to neurons.
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发表时间：
2017-12
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通讯作者：
Srinivasan V. Narayanan;M. Perez-Pinzon
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作者：
Srinivasan V. Narayanan;M. Perez-Pinzon
缺血预处理（IPC）是一种潜在的脑缺血治疗方法。虽然我们的小组以前已经表明IPC通过各种途径诱导神经保护，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。星形胶质细胞来源的乳酸作为一种潜在的可溶性介质引起了人们的注意，星形胶质细胞可以通过这种介质赋予神经元缺血耐受性。因此，本研究的目的是确定i）单独的星形胶质细胞的IPC处理是否可以将缺血耐受转移到神经元; ii）星形胶质细胞的IPC处理是否增加乳酸产生;以及iii）向神经元施用外源性乳酸是否可以诱导针对体外致死性缺血的神经保护。为此目的，使用共培养系统，并从先前的方法修改。该系统允许星形胶质细胞和神经元通过物理屏障分开，同时允许来自任一细胞类型的分泌物质相互作用。在培养的啮齿动物星形胶质细胞和神经元中，使用氧-糖剥夺作为脑缺血和IPC的模型。与假处理的星形胶质细胞孵育的神经元相比，IPC处理的星形胶质细胞孵育的神经元显着保护免受致命的缺血性损伤。此外，IPC处理的星形胶质细胞显着增加乳酸分泌到细胞外介质。最后，外源性乳酸的管理可以显着减弱细胞死亡后，暴露于致死OGD神经元培养。我们的研究结果表明，IPC处理星形胶质细胞单独可以转移缺血耐受神经元。此外，IPC增加星形胶质细胞中乳酸产生的能力表明，乳酸可以代表神经保护剂，以保护神经元免受致死性缺血损伤。
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.