The Application and Analytical Pathway of Dexmedetomidine in Ischemia/Reperfusion Injury

Abstract

Ischemia/reperfusion cerebral injury can cause serious damage to nerve cells. e injured organelles are cleared by autophagy eventually, which is critical for cell survival. Dexmedetomidine is neuroprotective in various ischemia/reperfusion models. Mitochondrial calcium uniporter (MCU) is the most important channel of mitochondrial Ca 2+ influx into mitochondria, where Ca 2+ has a potential effect on mitochondrial autophagy. However, the role of MCU in the changes of mitophagy and autophagy caused by dexmedetomidine is unknown. In this study, we constructed an in vitro I/R model by subjecting the oxygen and glucose deprivation/reperfusion model to SH-SY5Y cells to mimic the cerebral I/R injury. We found that postconditioning with dexmedetomidine and 3-methyladenine (3MA, an autophagy inhibitor) increased the cell survival meanwhile reduced the production of autophagic vesicles and the expression of LC3 and Beclin 1. is process also increased the expression of BCL-2, P62, and TOM20. After applied with spermine (MCU-specific agonist), the expression of autophagy proteins by dexmedetomidine was reversed, and the same changes were also observed in immunofluorescence. e results of our study suggested that dexmedetomidine can inhibit MCU and reduce excessive mitophagy and autophagy for conferring protection against I/R injury.

The potential role of dexmedetomidine on neuroprotection and its possible mechanisms: Evidence from in vitro and in vivo studies

“…J. Wu et al, 2017). Inhibition of mitochondrial calcium uniporter after dexmedetomidine treatment reduced excessive mitophagy and autophagy in SH-SY5Y cells (Tang et al, 2019). Dexmedetomidine also reduced -adrenoceptor subtype (Ma et al, 2004) mitochondrial apoptosis in rats with H/R-induced brain injury (Gao et al, 2019(Gao et al, , 2020.…”

“…In in vitro and in vivo, dexmedetomidine post treatment modulated neuronal apoptosis, mitochondrial function, inflammation, and oxidative stress (Chen, Cao, et al, 2019;Choi et al, 2017;Liu et al, 2017;C. Luo et al, 2017;Tang et al, 2019;Wang et al, 2018;G. J. Wu et al, 2017;M.…”

“…Dexmedetomidine reduced neuronal damage by modulating mitochondrial function (Akpinar et al, 2016;Gao et al, 2019Gao et al, , 2020C. Luo et al, 2017;Tang et al, 2019;G. J. Wu et al, 2017).…”

“…This pathway is essential for cellular homeostasis and dealing with stress conditions. Dexmedetomidine protected SH-SY5Y cells and rodents from ischaemic injury by inhibiting autophagy signalling (C. Luo et al, 2017;Tang et al, 2019;. In contrast, dexmedetomidine protected astrocytes from OGDinduced injury by activating autophagy via the TSC2/ mTOR pathway (C. Zhu et al, 2020).…”

Perioperative Dexmedetomidine attenuates brain ischemia reperfusion injury possibly via up-regulation of astrocyte Connexin 43

“…It could relieve neuronal necrosis and inflammation during I/R, as well as regulate GJs in astrocytes [ 7 ]. Dexmedetomidine may inhibit brain ischemia/reperfusion-induced neuroinflammation via activation of AMPK or reducing excessive mitophagy and autophagy [ 8 , 9 ]. It is reported that dexmedetomidine pretreatment can attenuate intestinal injury in intestinal ischemia-reperfusion rat model [ 10 ].…”