GABAA Receptor/STEP61 Signaling Pathway May Be Involved in Emulsified Isoflurane Anesthesia in Rats

Abstract

(1) Background: Emulsified isoflurane (EISO) is a type of intravenous anesthetic. How emulsified isoflurane works in the brain is still unclear. The aim of this study was to explore whether epigenetic mechanisms affect anesthesia and to evaluate the anesthetic effects of emulsified isoflurane in rats. (2) Methods: Rats were randomly divided into four groups (n = 8/group): The tail vein was injected with normal saline 0.1 mL·kg−1·min−1 for the control (Con) group, with intralipid for the fat emulsion (FE) group, with EISO at 60 mg·kg−1·min−1 for the high-concentration (HD) group, and 45 mg·kg−1·min−1 for the low-concentration (LD) group. The consciousness state, motor function of limbs, and response to nociceptive stimulus were observed after drug administration. (3) Results: Using real-time polymerase chain reaction (PCR) to assess the promoter methylation of ion channel proteins in the cerebral cortex of rats anesthetized by EISO, we demonstrated that the change in the promoters’ methylation of the coding genes for gamma-aminobutyric acid A receptor α1 subunit (GABAAα1), N-methyl-D-aspartate receptor subunit 1 (NMDAR1), and mu opioid receptor 1 (OPRM1) was accompanied by the change in messenger ribonucleic acid (mRNA) and protein expression by these genes. (4) Conclusion: These data suggest that the epigenetic factors’ modulation might offer a novel approach to explore the anesthetic mechanism of EISO.

Expression and Regulation of the GABAA Receptor/STEP61 Signaling Pathway in Cerebral Cortical Neurons Treated with Emulsified Isoflurane In Vitro

“…According to previous studies, mitogen-activated protein kinase (MAPK) plays a key role in the protective effect of EISO on ischemia-reperfusion and directly regulates OPRM. 37,19 In the present study, the increased expression of NF-κB, a downstream transcription factor of the P38 MAPK signaling pathway, did not correspond to decreased expression of NMDA receptors, which might be related to other transcription factors or the effect of methylation at the promotor region.…”

“…In our previous study, the administration of anesthesia to rats by a tail vein injection of emulsified isoflurane altered the expression of factors related to the GABA A /STEP61 signaling pathway and the methylation rate of genes encoding ligandgated ion channel proteins. 19 We cultured parietal cortical neurons and explored the changes in genes related to these signaling pathways in vitro to further clarify the actions of emulsified isoflurane.…”

Isoflurane alleviates systemic inflammation-induced neuroinflammation by decreasing the blood-brain barrier's damage and regulating the microglia's polarization

“…To make ISO act on cells more directly and precisely, pure ISO was added to 30% fat emulsion to prepare an 8% volume ratio of emulsi ed iso urane-solution vortexed at 50Hz for 2min every 10min, lasting 4 h [41]. They are then stored at 4℃.…”

The Bioequivalence of Emulsified Isoflurane With a New Formulation of Emulsion: A Single-Center, Single-Dose, Double-Blinded, Randomized, Two-Period Crossover Study

“…EI has greater C max and AUC (Yang et al, 2013). At some doses, the exposure of EI was greater than that of isoflurane (Huang et al, 2016;Wang et al, 2016;Yang et al, 2020;Zhao et al, 2020). In general, EI combines the advantages of both volatile and intravenous anesthetics (Huang et al, 2014), making it valuable in the clinical application (Zhou and Liu 2012).…”

“…Second, EI does not need the lung uptake to take effects; it also avoids the dilution of the drug resulting from the respiratory circuit and functional alveolar residue capacity; therefore, induction is faster ( Yang et al, 2008 ). Third, EI is eliminated mostly via expiration; anesthesia level can be easily controlled by injection speed and ventilation adjustment in the stage of anesthesia maintenance and emergence ( Huang et al, 2010 ; Zhou, et al, 2011b ; Huang et al, 2016 ; Wang et al, 2016 ; Yang et al, 2020 ; Zhao et al, 2020 ). Fourth, EI is more potent than isoflurane.…”