• Zheng Xu, Su-Wan Hu, Yu Zhou, Qingchen Guo, Di Wang, Yi-Hong Gao, Wei-Nan Zhao, Hui-Mei Tang, Jun-Xia Yang, Xiaolu Yu, Hai-Lei Ding, and Jun-Li Cao.
• Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou, China; NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, China.
• Br J Anaesth. 2023 Apr 1; 130 (4): 446458446-458.

BackgroundCorticotropin-releasing factor (CRF) neurones in the paraventricular nucleus (PVN) of the hypothalamus (PVNCRF neurones) can promote wakefulness and are activated under anaesthesia. However, whether these neurones contribute to anaesthetic effects is unknown.MethodsWith a combination of chemogenetic and molecular approaches, we examined the roles of PVNCRF neurones in isoflurane anaesthesia in mice and further explored the underlying cellular and molecular mechanisms.ResultsPVN neurones exhibited increased Fos expression during isoflurane anaesthesia (mean [standard deviation], 218 [69.3] vs 21.3 [7.3]; P<0.001), and ∼75% were PVNCRF neurones. Chemogenetic inhibition of PVNCRF neurones facilitated emergence from isoflurane anaesthesia (11.7 [1.1] vs 13.9 [1.2] min; P=0.001), whereas chemogenetic activation of these neurones delayed emergence from isoflurane anaesthesia (16.9 [1.2] vs 13.9 [1.3] min; P=0.002). Isoflurane exposure increased CRF protein expression in PVN (4.0 [0.1] vs 2.2 [0.3], respectively; P<0.001). Knockdown of CRF in PVNCRF neurones mimicked the effects of chemogenetic inhibition of PVNCRF neurones in facilitating emergence (9.6 [1.1] vs 13.0 [1.4] min; P=0.003) and also abolished the effects of chemogenetic activation of PVNCRF neurones on delaying emergence from isoflurane anaesthesia (10.3 [1.3] vs 16.0 [2.6] min; P<0.001). Acute, but not chronic, stress delayed emergence from isoflurane anaesthesia (15.5 [1.5] vs 13.0 [1.4] min; P=0.004). This effect was reversed by chemogenetic inhibition of PVNCRF neurones (11.7 [1.6] vs 14.7 [1.4] min; P=0.001) or knockdown of CRF in PVNCRF neurones (12.3 [1.5] vs 15.3 [1.6] min; P=0.002).ConclusionsCRF neurones in the PVN of the hypothalamus neurones modulate isoflurane anaesthesia and acute stress effects on anaesthesia through CRF signalling.Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

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