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小胶质细胞对暴露于过氧化氢诱导的氧化应激下的星形胶质细胞的保护作用的时间和激活依赖性。

Time- and activation-dependency of the protective effect of microglia on astrocytes exposed to peroxide-induced oxidative stress.

作者信息

Armbrust E, Röhl C

机构信息

Department of Anatomy, University of Kiel, Olshausenstrasse 40, D-24098 Kiel, Germany.

出版信息

Toxicol In Vitro. 2008 Aug;22(5):1399-404. doi: 10.1016/j.tiv.2008.02.008. Epub 2008 Feb 20.

DOI:10.1016/j.tiv.2008.02.008
PMID:18367369
Abstract

Microglial as well as astroglial activation (gliosis) are common phenomena of neuropathological processes in the brain. Nevertheless, the role of glial cell communication during gliosis is still not completely understood. The data we present with this work are a part of a bigger study on microglial-astroglial cell communication. The purpose of this study was to examine the impact of microglial-astroglial cell interactions on the cytotoxic effect of hydrogen peroxide (H2O2) on astrocytes and to characterize the microglia-induced astroprotective effect in detail. Therefore, purified cell cultures of microglia and astroglia from neonatal rat brains were used. Astrocytes were pre-treated with conditioned medium from lipopolysaccharides (LPS)-activated microglia and then exposed to oxidative stress induced by H2O2 under varying conditions. Activated microglia significantly reduced the cytotoxic effect of H2O2. As well in the indirect co-culture model using conditioned medium of microglia as in a direct co-culture model with different portions of microglial cells on the astroglial monolayer the astroprotective effect clearly correlated with the degree of microglial activation. The protective effect on astrocytes was induced in less than 24 h and lasted more than 4 days. Taken together, our results indicate that microglial activation might play an important role in the modulation of the oxidative stress resistance of glial tissue during gliosis.

摘要

小胶质细胞以及星形胶质细胞的激活(胶质增生)是大脑神经病理过程中的常见现象。然而,胶质增生过程中胶质细胞通讯的作用仍未完全明确。我们在这项工作中展示的数据是关于小胶质细胞 - 星形胶质细胞通讯的一项更大规模研究的一部分。本研究的目的是检测小胶质细胞 - 星形胶质细胞相互作用对过氧化氢(H₂O₂)对星形胶质细胞细胞毒性作用的影响,并详细表征小胶质细胞诱导的星形胶质细胞保护作用。因此,使用了从新生大鼠大脑中分离得到的纯化小胶质细胞和星形胶质细胞培养物。星形胶质细胞先用脂多糖(LPS)激活的小胶质细胞的条件培养基进行预处理,然后在不同条件下暴露于由H₂O₂诱导的氧化应激。活化的小胶质细胞显著降低了H₂O₂的细胞毒性作用。无论是在使用小胶质细胞条件培养基的间接共培养模型中,还是在星形胶质细胞单层上与不同比例小胶质细胞的直接共培养模型中,星形胶质细胞保护作用都与小胶质细胞活化程度明显相关。对星形胶质细胞的保护作用在不到24小时内诱导产生,并持续超过4天。综上所述,我们的结果表明,小胶质细胞活化可能在胶质增生过程中调节胶质组织氧化应激抗性方面发挥重要作用。

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引用本文的文献

1
Mechanisms involved in the modulation of astroglial resistance to oxidative stress induced by activated microglia: antioxidative systems, peroxide elimination, radical generation, lipid peroxidation.星形胶质细胞对激活的小胶质细胞诱导的氧化应激的抵抗的调节机制:抗氧化系统、过氧化物消除、自由基生成、脂质过氧化。
Neurotox Res. 2010 May;17(4):317-31. doi: 10.1007/s12640-009-9108-z. Epub 2009 Sep 10.