• Dan Wang, Yongxin Guo, Huiming Li, Jiannan Li, Mingzi Ran, Juan Guo, Lu Yin, Shiyi Zhao, Qianzi Yang, and Hailong Dong.
• Department of Anaesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
• Br J Anaesth. 2021 Jan 1; 126 (1): 279-292.

BackgroundThe neuropeptide orexin promotes arousal from general anaesthesia, however the neuronal circuits that mediate this effect have not been defined. We investigated whether orexinergic neurones modulate the basal forebrain (BF) and locus coeruleus (LC) in emergence from anaesthesia.MethodsHcrtcre rats were generated using a CRISPR/Cas9-based approach. Viruses encoding optogenetic probes were injected into the perifornical lateral hypothalamic (PeFLH) area, optogenetic fibres were embedded in the PeFLH, BF, or LC, and changes in anaesthesia state under 1.4 vol% or 0.8 vol% isoflurane were determined.ResultsIn the PeFLH, 98.8% (0.4%) of orexin-A-positive cells expressed tdTomato, and 91.9% (2.2%) of tdTomato cells were orexin-A-positive. Under 1.4 vol% isoflurane anaesthesia, compared with control groups, burst suppression ratio was less, and emergence time was shorter in groups with optogenetic activation of orexinergic cell bodies in the PeFLH (923 [162] vs 493 [68] s, P=0.0003) or orexinergic terminals in the BF (937 (122) vs 674 (108) s, P=0.0049) or LC (913 [128] vs 742 [76] s, P=0.022). Optical stimulation of orexinergic terminals in the BF and LC also improved the movement scores of rats under 0.8 vol% isoflurane anaesthesia.ConclusionsActivation of orexinergic terminals in the FB or LC mediates facilitation of emergence from anaesthesia by orexinergic neurones during isoflurane anaesthesia.Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

25 keywords...

hide…