Identification of Brain Regions Activated by Sevoflurane and Propofol and Regional Changes in Gene Expression

Abstract

General anesthetics have different efficacies and side effect incidences based on their mechanism of action. However, detailed comparative studies of anesthetics are incomplete. In this study, target brain regions and gene expression changes in these brain regions were determined for sevoflurane and propofol to understand the mechanisms that cause differences among anesthetics. Rats were anesthetized with sevoflurane or propofol for 1 hr, and brain regions with anesthesia-induced changes in neuronal activity were examined by immunohistochemistry and in situ hybridization for c-Fos. Among the identified target brain regions, gene expression analysis was performed in the habenula, the solitary nucleus and the medial vestibular nucleus from laser microdissected samples. Genes altered by sevoflurane and propofol were different and included genes involved in the incidence of postoperative nausea and vomiting and emergence agitation, such as Egr1 and Gad2. GO enrichment analysis showed that the altered genes tended to be evenly distributed in all functional category. The detailed profiles of target brain regions and induced gene expression changes of sevoflurane and propofol in this study will provide a basis for analyzing the effects of each anesthetic agent and the risk of adverse events.

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“…After hybridization, the same procedure was performed as described above. The specificity of the Fos probe has been confirmed previously by hybridizing with a sense probe as a negative control [38].…”

“…After washing, the sections were incubated with Alexa Fluor 568-conjugated donkey anti-mouse IgG antibody (1:500) and Alexa Fluor 488-conjugated donkey anti-rabbit IgG antibody (1:500, Cat# A-21206, RRID:AB_2535792; Thermo Fisher Scientific Inc.) for 2 h at RT. The specificities of anti-GnRH antibody [40] and antic-Fos antibody [38] have been described previously.…”

“…In free-floating method, brain sections containing POA were incubated with anti-GnRH mouse monoclonal antibody (1:1000; LRH13, RRID: AB 2636958, kindly provided by Dr. Min Kyun Park, The University of Tokyo, Japan) and anti-c-Fos rabbit polyclonal antibody (1:1000, Cat# 226003, RRID:AB 2231974; Synaptic Systems, Göttingen, Germany) overnight at 4 • C. After washing, the sections were incubated with Alexa Fluor 568-conjugated donkey antimouse IgG antibody (1:500) and Alexa Fluor 488-conjugated donkey anti-rabbit IgG antibody (1:500, Cat# A-21206, RRID:AB 2535792; Thermo Fisher Scientific Inc.) for 2 h at RT. The specificities of anti-GnRH antibody [40] and antic-Fos antibody [38] have been described previously.…”

Carnosol alleviates sevoflurane‑induced cognitive dysfunction by mediating NF‑κB pathway in aged rats

“…Studies of brain activity during SEV‐induced loss of consciousness have found that not only are cerebral blood flow altered in frontal, parietal, and thalamic regions, but also abnormal brain metabolic activity (Oshima et al, 2003; Zhu et al, 2020). In addition, several recent studies have found that SEV also weakens signaling linkages between brain regions, induces cytotoxicity, and induces mitophagy to mediate apoptosis (Kafashan et al, 2016; Kamei et al, 2022; Yang et al, 2017; J. M. Zhang & An, 2007).…”