Drug Design, Development and Therapy (Oct 2018)
Dexmedetomidine protects the developing rat brain against the neurotoxicity wrought by sevoflurane: role of autophagy and Drp1–Bax signaling
Abstract
Yangyang Shan,1 Shiwei Sun,1 Fan Yang,1 Nan Shang,2 Hongtao Liu11Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang, 110004, China; 2Department of Respiration, No. 202 Hospital of PLA, Shenyang, 110003, ChinaBackground: The effect of sevoflurane on the nervous system is controversial. As an adjuvant anesthetic, dexmedetomidine has a protective role in various nerve-injury diseases. We investigated the effect of dexmedetomidine on injury to the developing brain induced by sevoflurane anesthesia, and if autophagy and mitochondrial damage are involved in the neuroprotective effects of dexmedetomidine.Methods: Pregnant rats on gestational day 20 were exposed to 3% sevoflurane for 4 hours. Saline and dexmedetomidine were injected intraperitoneally 15 minutes before exposure to sevoflurane or control gas. Bilateral hippocampi were harvested on postnatal day 1. Hippocampal morphology was observed by Nissl staining and expression of the microtubule-related protein LC3I/II, p62, Drp1, Bax, and Bcl2 were evaluated by Western blotting and immunohistochemistry.Results: Nissl staining showed that sevoflurane anesthesia during the third trimester caused neuronal damage to the hippocampi of rat pups. Western blotting and immunohistochemistry showed that pregnant rats exposed to sevoflurane during the third trimester led to pups having increased expression of LC3 and p62, suggesting that sevoflurane blocked autophagic flow in the hippocampus. Expression of Drp1 and Bax was increased after sevoflurane exposure, whereas Bcl2 expression was downregulated. All these effects were alleviated by pretreatment with dexmedetomidine.Conclusion: Sevoflurane exposure during the third trimester caused neurological injury to rat pups. Autophagy and abnormalities in mitochondrial dynamics were involved in this neurotoxic process and were antagonized by dexmedetomidine. Keywords: dexmedetomidine, sevoflurane, autophagy, Drp1, developing brain
