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Sulbactam Plays Neuronal Protective Effect Against Brain Ischemia via Upregulating GLT1 in Rats

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Abstract

The study was undertaken to investigate whether sulbactam protects cerebral neurons against ischemia and whether the protection is mediated by regulating the expression and uptake activity of glial glutamate transporter-1 (GLT1) in a rat global brain ischemia model. The CA1 hippocampus was selected as the observing target. Real time quantitative PCR, Western blot and immunohistochemistry assays were used to detect GLT1 expression. Neuropathological evaluation was performed after thionin staining to determine the extent of the delayed neuronal death (DND) of pyramidal neurons. It was found that cerebral ischemia for 8 min induced obvious DND of pyramidal neurons and GLT1 downregulation. Sulbactam pretreatment significantly upregulated GLT1 expression in sham rats and prevented or reversed the GLT1 downregulation normally induced in the ischemic rat brain. Meanwhile, sulbactam pretreatment effectively prevented the DND of pyramidal neurons normally induced by brain ischemia in a dose-dependent manner. Sulbactam posttreatment also protected pyramidal neurons against DND induced by brain ischemia although the magnitude of the protective effect was weaker than that in sulbactam pretreatment. Furthermore, either antisense knockdown of GLT1 expression or inhibition of the GLT1 uptake activity with dihydrokainate, a selective inhibitor of GLT1, significantly blocked the neuronal protective effect of sulbactam. These findings indicate that sulbactam has a neuronal protective effect though upregulating GLT1.

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Acknowledgments

This work was supported by the following foundations: (1) National Natural Science Foundation of China (No: 81271454, No: 31271149, No: 81000477 and No: 31100781); (2) Key Basic Research Project in Application Plan of Hebei Province, P.R. China (No: 11966121D); and (3) Special Foundation for Doctoral Education in University from Ministry of Education, PR China (No: 20111323110005).

Conflict of Interest

No author has a conflict of interest in this study.

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Authors and Affiliations

  1. Department of Pathophysiology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017, People’s Republic of China

    Xin Cui, Yu-Yan Hu, Shuang Ren, Min Zhang & Wen-Bin Li

  2. Department of Science and Technology, The Second Hospital of Hebei Medical University, 215 Heping West Road, Shijiazhuang, 050000, People’s Republic of China

    Li Li

  3. Aging and Cognition Neuroscience Laboratory of Hebei Province, 89 Donggang Road, Shijiazhuang, 050031, People’s Republic of China

    Wen-Bin Li

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  1. Xin Cui
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Correspondence to Wen-Bin Li.

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Cui, X., Li, L., Hu, YY. et al. Sulbactam Plays Neuronal Protective Effect Against Brain Ischemia via Upregulating GLT1 in Rats. Mol Neurobiol 51, 1322–1333 (2015). https://doi.org/10.1007/s12035-014-8809-3

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  • DOI: https://doi.org/10.1007/s12035-014-8809-3

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