Abstract
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.
Highlights
Cerebral infarction, known as ischemic stroke, is the most common neurological disease
Sigma-1 receptor (Sig-1R) expression was significantly lower in the middle cerebral artery occlusion (MCAO) group than in the sham group, but this decrease was significantly attenuated in the MCAO + dexmedetomidine group (P
GRP78 expression was significantly lower in the MCAO + BD1063 + dexmedetomidine group than in the MCAO + dexmedetomidine group (P
Summary
Known as ischemic stroke, is the most common neurological disease. The incidence of cerebral infarction has been increasing, creating an enormous burden for families and society. No effective treatment has been found for this common disease [1]. The tissues are damaged to varying degrees, and the damage is often irreversible. After a period of ischemia, the blood supply to the brain gradually recovers, but a large number of nerve cells fail to return to normal function in time. This can cause more serious neurological damage, in what is called cerebral ischemia-reperfusion injury (CIRI) [2]. CIRI leads to neuronal death in the core area of the occlusive www.aging-us.com artery within a few minutes, while a certain number of surviving but vulnerable neurons form an ischemic penumbra around the core area [3]
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