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

Abstract

Background Astrocyte Connexin 43 (Cx43) is essential for the trophic and protective support of neurons during brain ischemia reperfusion (I/R) injury. It is believed that dexmedetomidine participates in Cx43-mediated effects. However, its mechanisms remained unclear. This study aims to address the relationship and regulation among them. Methods Adult male Sprague-Dawley rats were allocated to the 90-min right middle cerebral arterial occlusion with or without dexmedetomidine pretreatment (5 μg/kg). Neurological functions were evaluated and brain lesions, as well as inflammatory factors (IL-1β, IL-6, TNF-α), were assessed. Ischemic penumbral cortex was harvested to determine the expression of astrocyte Cx43. Primary astrocytes were cultured to evaluate the effect of dexmedetomidine on Cx43 after oxygen-glucose deprivation. Results Dexmedetomidine pretreatment attenuated neurological injury, brain lesions and expression of inflammatory factors (IL-1β, IL-6, TNF-α) after brain ischemia (P < 0.05). Astrocyte Cx43 was down-regulated by brain I/R injury, both in vivo and in vitro, which were reversed by dexmedetomidine (P < 0.05). This effect was mediated by the phosphorylation of Akt and GSK-3β. Further studies with LY294002 (PI3K inhibitor) or SB216763 (GSK-3β inhibitor) confirmed the effect of dexmedetomidine on astrocyte Cx43. Conclusions Perioperative dexmedetomidine administration attenuates neurological injury after brain I/R injury, possibly through up-regulation of astrocyte Cx43. Activation of PI3K-Akt-GSK-3β pathway might contribute to this protective effect.

Neurovascular protection of alisol A on cerebral ischemia mice through activating the AKT/GSK3β pathway

“…Microglia-mediated inflammation affects basal lamina integrity and leads to increased permeability of the BBB, ultimately resulting in significant neurovascular disruption [ 35 ]. A previous study showed that the activation of AKT/GSK3β inhibited the proinflammatory “M1” phenotype of microglia and then downregulated IL-6, IL-1β and TNF-α levels [ 36 – 38 ]. The present study showed that alisol A significantly inhibited the expression of GFAP and Iba1 and reduced the overactivation of glial cells.…”

Effect of dexmedetomidine administration on analgesic, respiration and inflammatory responses in patients undergoing percutaneous endoscopic lumbar discectomy: a prospective observational study

“…The significant reduction in the VAS in Group A reveals that DEX could provide analgesia during PELD so as to attenuate inflammatory response and pain-induced oxidative stress. According to the previous study, perioperative DEX administration can effectively reduce the generation of inflammatory mediators in the plasma, which relys on TLR4/MyD88/MAPK/ NF-κB signaling pathway and PI3K-Akt-GSK-3βsignaling pathway [ 24 , 25 ]. In addition, through amelioration of HMGB1-NLRP3 inflammasome-AMPK signaling could DEX play protective action [ 26 ] and DEX has STAT3-dependent anti-inflammatory effects to attenuate the tissue inflammatory cascade response by modulating the JAK2/STAT3 signaling pathway [ 27 ].…”

Dexmedetomidine alleviates oxygen and glucose deprivation-induced apoptosis in mesenchymal stem cell via downregulation of MKP-1

“…In another study, Zhai et al (2019) highlighted that Dex attenuates ischemia-induced neuronal apoptosis (Zhai et al, 2019). Dex can protect both cardiomyocytes (Chang et al, 2020) and neurons (Zheng et al, 2020) against ischemia-reperfusion injury through the inhibition of apoptosis. Based on the above findings, we hypothesize that Dex might protect MSCs against ischemia-induced cell death.…”