Research Paper Volume 11, Issue 21 pp 9556—9568
Dexmedetomidine inhibits neuronal apoptosis by inducing Sigma-1 receptor signaling in cerebral ischemia-reperfusion injury
- 1 Department of Anesthesiology, Tianjin Central Hospital of Gynecology Obstetrics, Gynecology Obstetrics Hospital of Nankai University, Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin 300052, China
- 2 Department of Anesthesiology, Central Laboratory, Tianjin 4th Centre Hospital, The Fourth Central Hospital Affiliated to Nankai University, Tianjin 300140, China
- 3 Department of Anesthesiology, Tianjin Xiqing Hospital, Tianjin 300380, China
- 4 Department of Neurology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang Province 318000, China
received: August 8, 2019 ; accepted: October 26, 2019 ; published: November 4, 2019 ;https://doi.org/10.18632/aging.102404
How to Cite
Copyright © 2019 Zhai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Dexmedetomidine is known to alleviate cerebral ischemia-reperfusion injury (CIRI). We established a rat model of CIRI, which exhibited higher neurological deficit scores and a greater number of apoptotic cells in the cerebral ischemic penumbra than controls. Dexmedetomidine reversed the neuronal apoptosis and improved neurological function in this model. We then examined Sigma-1 receptor (Sig-1R) expression on the endoplasmic reticulum (ER) in brain tissues at different reperfusion time points. Sig-1R expression increased with CIRI and decreased with increasing reperfusion times. After 24 hours of reperfusion, dexmedetomidine upregulated Sig-1R expression, and ER stress proteins (GRP78, CHOP, JNK and Caspase-3) were detected in brain tissues with Western blotting. Moreover, GRP78 expression followed a pattern similar to Sig-1R. Dexmedetomidine induced GRP78 expression but inhibited CHOP, Caspase-3 and phosphorylated-JNK expression in brain tissues. A Sig-1R-specific inhibitor reduced GRP78 expression and partially inhibited the upregulation of GRP78 by dexmedetomidine. The inhibitor also increased CHOP and Caspase-3 expression and partially reversed the inhibitory effects of dexmedetomidine on these pro-apoptotic ER stress proteins. These results suggest that dexmedetomidine at least partially inhibits ER stress-induced apoptosis by activating Sig-1R, thereby attenuating brain damage after 24 hours of ischemia-reperfusion.