The differential effects of isoflurane and sevoflurane on neonatal mice

Abstract

Previous research has shown that exposure to volatile anesthetics can induce acute neuroinflammation and neuroapoptopsis in neonatal rodents and that these events can lead to cognitive dysfunction at later stages. Isoflurane and sevoflurane are two of the most popular anesthetics used in the field of pediatrics. However, the relative impact of these two anesthetics on the developing brain at distinct time points after the induction of anesthesia has not been compared. In the present study, we exposed 7-day-old mice to clinically equivalent doses of isoflurane (1.5%) and sevoflurane (2.5%) for 4 h and then investigated consequential changes in the brains of these mice at six different time points. We analyzed the levels of proteins that are directly related to neuroapoptosis, neuroinflammation, synaptic function, and memory, in the brains of neonatal mice. Exposure of neonatal mice to isoflurane and sevoflurane resulted in acute neuronal apoptosis. Our analysis observed significant levels of neuroinflammation and changes in the expression levels of proteins associated with both synaptic transmission and memory in mice from the isoflurane group but not the sevoflurane group. Our results therefore indicate that isoflurane and sevoflurane induce differential effects in the brains of neonatal mice.

Sevoflurane-Induced Apoptosis in the Mouse Cerebral Cortex Follows Similar Characteristics of Physiological Apoptosis

“…Isoflurane is also a commonly used volatile anesthetic in clinical and has frequently been reported to induce widespread apoptotic neurodegeneration when administered to neonatal animals. Despite the similar effects on enhancing GABA A receptor function and activating certain types of K + channels, isoflurane has been reported to induced a significantly greater amount of apoptotic neurons in different brain regions than an equipotent exposure of sevoflurane (Liang et al, 2010;Zhao et al, 2020). Isoflurane induced neuronal apoptosis in neonatal brain mainly by activation the mitochondrial pathway, while sevoflurane is more prone to causing endoplasmic reticulum (ER) stress-induced apoptosis (Zhao et al, 2020).…”

“…Despite the similar effects on enhancing GABA A receptor function and activating certain types of K + channels, isoflurane has been reported to induced a significantly greater amount of apoptotic neurons in different brain regions than an equipotent exposure of sevoflurane (Liang et al, 2010;Zhao et al, 2020). Isoflurane induced neuronal apoptosis in neonatal brain mainly by activation the mitochondrial pathway, while sevoflurane is more prone to causing endoplasmic reticulum (ER) stress-induced apoptosis (Zhao et al, 2020). In terms of the vulnerable cell population targeted by isoflurane, more detailed observation have been reported on neonatal non-human primates (NHPs).…”

Ganoderma lucidum polysaccharide ameliorated diabetes mellitus-induced erectile dysfunction in rats by regulating fibrosis and the NOS/ERK/JNK pathway

“…Members of the caspase family are regarded as crucial mediators for mitochondrial-mediated apoptosis, among which caspase-3 and caspase-9 are representative executors ( 32 ). Activated caspase-9 triggers the activation of caspase-3, which in turn cleaves its protein substrate and finally induces apoptosis ( 33 ).…”

Dual roles of anesthetics in postoperative cognitive dysfunction: Regulation of microglial activation through inflammatory signaling pathways

“…Additionally, prolonged isoflurane inhalation for 6 h leads to microglial activation and M1 polarization via the upregulation of TLR4/NF-kB pathway (98,99), and cognitive impairment correlates directly with the multiple isoflurane exposures (139). One study comparing the pro-inflammatory properties of isoflurane with sevoflurane, discovered that at equivalent doses, isoflurane induces a significantly greater neuroinflammatory response (96), although whether this leads to more severe cognitive impairment remains to be explored.…”