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Hypoxic Preconditioning Attenuates Neuronal Cell Death by Preventing MEK/ERK Signaling Pathway Activation after Transient Global Cerebral Ischemia in Adult Rats

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Abstract

Our previous data indicated that hypoxic preconditioning (HPC) ameliorates transient global cerebral ischemia (tGCI)-induced neuronal death in hippocampal CA1 subregion of adult rats. However, the possible molecular mechanisms for neuroprotection of this kind are largely unknown. This study was performed to investigate the role of the mitogen-activated protein kinase/extra-cellular signal-regulated kinase kinase (MEK)/extra-cellular signal-regulated kinase (ERK) pathway in HPC-induced neuroprotection. tGCI was induced by applying the four-vessel occlusion method. Pretreatment with 30 min of hypoxia applied 1 day before 10 min tGCI significantly decreased the level of MEK1/2 and ERK1/2 phosphorylation in ischemic hippocampal CA1 subregion. Also, HPC decreased the expression of phosphorylated ERK1/2 in degenerating neurons and astrocytes. However, the administration of U0126, a MEK kinase inhibitor, partly blocked MEK1/2 and ERK1/2 phosphorylation induced by tGCI. Meanwhile, neuronal survival was improved, and glial cell activation was significantly reduced. Collectively, these data indicated that the MEK/ERK signaling pathway might be involved in HPC-induced neuroprotection following tGCI. Also, HPC resulted in a reduction of glial activation.

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Acknowledgments

This work was supported by National Research Foundation for the Doctoral Program of Higher Education of China (Grant No. 20124423110002), and partly supported by the National Natural Science Foundation of China (Grant No. 81100800). Our sincere thanks go to Mr. Peifeng DU (Institute for Standardization of Nuclear Industry) and Donghai Liang (Environmental Health Sciences, Yale School of Public Health) for editing this paper.

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Authors and Affiliations

  1. Institute of Neurosciences and the Second Affiliated Hospital of Guangzhou Medical College, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, 510260, People’s Republic of China

    Lixuan Zhan, Hongxin Yan, Huarong Zhou, Weiwen Sun, Qinghua Hou & En Xu

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  1. Lixuan Zhan
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  2. Hongxin Yan
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Correspondence to En Xu.

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Zhan, L., Yan, H., Zhou, H. et al. Hypoxic Preconditioning Attenuates Neuronal Cell Death by Preventing MEK/ERK Signaling Pathway Activation after Transient Global Cerebral Ischemia in Adult Rats. Mol Neurobiol 48, 109–119 (2013). https://doi.org/10.1007/s12035-013-8436-4

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