Cerebral Protection of Intraoperative Infusion of Dexmedetomidine in Patients with Chronic Cerebrovascular Stenosis Undergoing Endovascular Interventional Therapies: A Prospective Randomized Controlled Trial.

BACKGROUND: To investigate the cerebral protective effect of intraoperative dexmedetomidine infusion on patients with chronic cerebral vascular stenosis receiving endovascular interventional therapy. METHODS: Sixty patients with carotid artery or cerebral artery stenosis or occlusion stenting under elective general anesthesia were divided into dexmedetomidine group (group D) and normal saline group (group N). Group D was given dexmedetomidine loading dose 1.0 µg/kg after peripheral vein opening for 10 min, and then adjusted infusion rate to 0.5 µg/kg/h until stopped 30 min before end. RESULTS: At 7 days after operation, the contents of S100ß, neuron-specific enolase (NSE) and interleukin-6 (IL-6) in group D were apparently lower than those in group N (P < 0.05), while the contents of IL-1ß and tumor necrosis factor-α in 2 groups showed no statistical significance (P > 0.05). Additionally, at 4 days and 7 days after operation, the scores of Mini-Mental State Scale (MMSE) and Wechsler Memory Scale (WMS) in group D were significantly higher than those in group N (P < 0.05). Thirty days after surgery, the cerebral hemodynamic indexes (relative mean transit time, relative time to peak) in group D were significantly improved, and obviously better than those in group N (P < 0.05). CONCLUSIONS: The S-100ß, NSE, and inflammatory mediator IL-6 in group D were significantly decreased compared with group N, the MMSE and WMS cognitive function scores, and the cerebral blood perfusion were apparently improved in group D, clarifying dexmedetomidine has protective effect on nerve tissue injury by inhibiting inflammation.

Dexmedetomidine inhibits inflammatory response and oxidative stress through regulating miR-205-5p by targeting HMGB1 in cerebral ischemic/reperfusion.

OBJECTIVE: To investigate effects of dexmedetomidine (DEX) on miR-205-5p/HMGB1 axis in cerebral ischemic/reperfusion (I/R) injury. METHODS: Both in vivo I/R rat model and in vitro hypoxia/reoxygenation (H/R) cell model using rat hippocampal neurons cells were established. miR-205-5p was overexpressed or inhibited by transfection of miR-205-5p mimics or inhibitor. HMGB1 was overexpressed by transfection overexpression plasmids (OE-HMGB1). TTC staining was used for measurement of infraction volume. Oxidative stress was evaluated by measurement of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) and inflammation was evaluated by measurement of IL-1ß, IL-6 and TNF-α. Dual luciferase reporter assay was performed to confirm binding between miR-205-5p and HMGB1. The expression levels of miR-205-5p, and HMGB1 were measured using RT-qPCR. Western blotting was used to test the protein expression levels of HMGB1, nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase (GPx), glutathione reductase (GR), heme oxygenase 1 (HO-1) and catalase (CAT). RESULTS: Treatment of DEX significantly reduced brain infraction volume, decreased Longa's neurological function score and inhibited oxidative stress and inflammation in brain tissues of I/R rats, which were all reversed by inhibition of miR-205-5p. Both treatment of DEX or overexpression of miR-205-5p restricted oxidative stress and inflammation in H/R rat hippocampal neurons cells. The inhibition of miR-205-5p reversed the effects of DEX, while the overexpression of HMGB1 reversed the effects of miR-205-5p overexpression in H/R rat hippocampal neurons cells. Dual luciferase reporter assay showed miR-205-5p directly targeted HMGB1. CONCLUSION: DEX improved I/R injury by suppressing brain oxidative stress and inflammation DEX improved I/R injury by suppressing brain oxidative stress and inflammation through activating miR-205-5p/HMGB1 axis through activating miR-205-5p/HMGB1 axis.