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Activation of mGluR5 Attenuates Microglial Activation and Neuronal Apoptosis in Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats

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Abstract

Activation of metabotropic glutamate receptor 5 (mGluR5) provided neuroprotection in multiple central nervous system injury, but the roles of mGluR5 in subarachnoid hemorrhage (SAH) remain unclear. In present study, we aimed to evaluate whether activation of mGluR5 attenuates early brain injury (EBI) after experimental SAH in rats. We found that selective mGluR5 orthosteric agonist CHPG or positive allosteric modulator VU0360172 administration significantly improves neurological function and attenuates brain edema at 24 h after SAH. Furthermore, mGluR5 obviously expresses in activated microglia (ED-1 positive) after SAH. CHPG or VU0360172 administration significantly reduces the numbers of activated microglia and the protein and mRNA levels of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α at 24 h after SAH. Moreover, CHPG or VU0360172 administration obviously reduces the number of TUNEL-positive cells and active caspase-3/NeuN-positive neurons in cortex at 24 h after SAH. CHPG or VU0360172 administration significantly up-regulates the expression of Bcl-2, and down-regulates the expression of Bax and active caspase-3, which in turn increases the ratio of Bcl-2/Bax. Our results indicate that activation of mGluR5 attenuates microglial activation and neuronal apoptosis, and improves neurological function in EBI after SAH.

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Acknowledgments

The National Natural Science Foundation of China (NSFC) (No. 81301018, No. 81271275 and No. 31100548) supported this work.

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The authors declare that they have no conflict of interest.

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    Authors and Affiliations

    1. Key Lab of Cerebral Microcirculation at the Universities of Shandong, Life Science Research Centre of Taishan Medical University, Taian, 271016, Shandong, China

      Zong-yong Zhang, Bao-liang Sun, Ming-feng Yang, Da-wei Li, Jie Fang & Shuai Zhang

    2. Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China

      Jun-ke Liu, Qi-lin Yuan & Si-luo Huang

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    1. Zong-yong Zhang
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    Correspondence to Zong-yong Zhang or Si-luo Huang.

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    Zong-yong Zhang and Bao-liang Sun have contributed equally to this work.

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    Zhang, Zy., Sun, Bl., Liu, Jk. et al. Activation of mGluR5 Attenuates Microglial Activation and Neuronal Apoptosis in Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats. Neurochem Res 40, 1121–1132 (2015). https://doi.org/10.1007/s11064-015-1572-7

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