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Cellular and Molecular Neurobiology

, Volume 37, Issue 4, pp 743–752 | Cite as

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

  • Fuxing Dong
  • Ruiqin Yao
  • Hongli Yu
  • Yaping Liu
Original Research

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.

Keywords

Ro25-6981 Ischemia/reperfusion Autophagy N-methyl-d-aspartate receptor 

Notes

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).

Compliance with Ethical Standards

Conflict of interest

All authors declare that there is no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Fuxing Dong
    • 1
  • Ruiqin Yao
    • 1
  • Hongli Yu
    • 1
  • Yaping Liu
    • 2
  1. 1.Research Center for NeurobiologyXuzhou Medical UniversityXuzhouPeople’s Republic of China
  2. 2.Laboratory of National Experimental Teaching and Demonstration Center of Basic MedicineXuzhou Medical UniversityXuzhouPeople’s Republic of China

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