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Neuroprotection of Ro25-6981 Against Ischemia/Reperfusion-Induced Brain Injury via Inhibition of Autophagy

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Abstract

In this study, we investigated the neuroprotective effect of Ro25-6981 against cerebral ischemia/reperfusion injury. Ro25-6981 alone or in combination with rapamycin was intracerebroventricularly administered to rats which suffered transient forebrain ischemia inducing by 4-vessel occlusion and reperfusion. Nissl staining was used to determine the survival of CA1 pyramidal cells of the hippocampus, while immunohistochemistry was performed to measure neuron-specific enolase (NSE) expression. The expression of autophagy-related proteins, such as microtubule-associated protein l light chain 3 (LC3), Beclin 1, and sequestosome 1 (p62), was assessed by immunoblotting. Nissl staining showed that neuronal damage was reduced in the hippocampal CA1 pyramidal layer in rats that received Ro25-6981. The protective effect of Ro25-6981 was dose-dependent, with a significant effect in the middle-dose range. The expression of NSE increased after Ro25-6981 treatment. Ro25-6981 significantly decreased LC3II (which is membrane bound) and Beclin 1, and increased p62. In addition, Ro25-6981 decreased rapamycin-induced neuronal damage and excessive activation of autophagy after I/R. Taken together, the results suggest that Ro25-6981 could suppress ischemic brain injury by regulating autophagy-related proteins during ischemia/reperfusion.

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Acknowledgments

This work was supported by National Natural Science Foundation of China (81271345), the Natural Science Foundation of Jiangsu Higher Education Institutions of China (15KJB180018), and Project of Xuzhou Science and Technology (KC15SH009).

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  1. Research Center for Neurobiology, Xuzhou Medical University, No. 209, Tongshan Road, Yunlong District, Xuzhou, 221004, Jiangsu, People’s Republic of China

    Fuxing Dong, Ruiqin Yao & Hongli Yu

  2. Laboratory of National Experimental Teaching and Demonstration Center of Basic Medicine, Xuzhou Medical University, No. 209, Tongshan Road, Yunlong District, Xuzhou, 221004, Jiangsu, People’s Republic of China

    Yaping Liu

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  1. Fuxing Dong
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  2. Ruiqin Yao
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Dong, F., Yao, R., Yu, H. et al. Neuroprotection of Ro25-6981 Against Ischemia/Reperfusion-Induced Brain Injury via Inhibition of Autophagy. Cell Mol Neurobiol 37, 743–752 (2017). https://doi.org/10.1007/s10571-016-0409-5

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