Repeated inhalation of sevoflurane inhibits the information transmission of Purkinje cells and delays motor development via the GABAA receptor ε subunit in neonatal mice

Abstract

General anesthesia is widely used in pediatric surgery, although the influence of general anesthesia on cerebellar information transmission and motor function is unclear. In the present study, neonatal mice received repeated inhalation of sevoflurane, and electrophysiological alterations in Purkinje cells (PCs) and the development of motor functions were detected. In addition, γ-aminobutyric acidA receptor ε (GABAA-R ε) subunit knockout mice were used to investigate the mechanism of action of sevoflurane on cerebellar function. In the neonatal mice, the field potential response of PCs induced by sensory stimulation and the motor function indices were markedly inhibited by sevoflurane, and the inhibitory effect was positively associated with the number of repetitions of anesthesia. In additional the GABAA-R ε subunit level of PCs was promoted by sevoflurane in a dose-dependent manner, and the inhibitory effects of sevoflurane on PC field potential response and motor function were alleviated in GABAA-R ε subunit knockout mice. The GABAA-R ε subunit was activated by sevoflurane, leading to inhibition of sensory information transmission in the cerebellar cortex, field potential responses of PCs and the development of cerebellar motor function. The present study provided experimental evidence for the safe usage of sevoflurane in clinical anesthesia, and suggested that GABAA-R ε subunit antagonists may be considered for combined application with general anesthesia with repeated inhalation of sevoflurane, for adverse effect prevention in the clinic.

Ferroptosis involved in sevoflurane-aggravated young rats brain injury induced by liver transplantation

“…Exposure to sevoflurane increased iron content in hippocampal neurons compared with cells not exposed to sevoflurane [ 29 ]. Sevoflurane enhances oxidative stress in the neonatal rat brains and induces ROS production and neuronal cell death [ 30 ]. However, it is unknown whether sevoflurane can affect brain injury after liver transplantation in young rats by modulating ferroptosis.…”

A narrative review of the impact of cerebellar dysfunction and sleep disturbances after general anesthesia in patients with Alzheimer’s disease

“…However, even at low doses, propofol treatment reduces the levels of Notch1 and Jagged1, which promotes Bergmann glial cell reduction and Bergmann abnormal processes, further slowing down granule cell migration and weakening of cerebellar PC development (33). Fang et al noted that the inhalation of sevoflurane seemed to inhibit sensory information transmission in the cerebellar cortex and had a partially dose-dependent effect, further delaying cerebellar motor function development (34). Moreover, inhaled anesthetics may also increase the level of small oligomers in the cerebellum (35), such as Aβ peptide aggregates, and impair learning and memory function in AD.…”

The Effects of YAP and Its Related Mechanisms in Central Nervous System Diseases

“…Purkinje cells are an important part of the signal transmission (Fang et al, 2018), and dendritic dysfunction can cause the related signal transmission to be blocked. The current study found that the YAP signaling pathway can maintain the normal structure of the Purkinje cell dendrites, thereby promoting normal cerebellum morphology and motor coordination function (Liu et al, 2017).…”