Sevoflurane is a widely used inhalational anesthetic in pediatric surgeries, which is considered reasonably safe and reversible upon withdrawal. However, recent preclinical studies suggested that peri-neonatal sevoflurane exposure may cause developmental abnormalities in the brain. The present review aimed to present and discuss the accumulating experimental data regarding the undesirable effects of sevoflurane on brain development as revealed by the laboratory studies. First, we summarized the long-lasting side effects of neonatal sevoflurane exposure on cognitive functions. Subsequently, we presented the structural changes, namely, neuroapoptosis, neurogenesis and synaptogenesis, following sevoflurane exposure in the immature brain. Finally, we also discussed the potential mechanisms underlying subsequent cognitive impairments later in life, which are induced by neonatal sevoflurane exposure and pointed out potential strategies for mitigating sevoflurane-induced long-term cognitive impairments. The type A gamma-amino butyric acid (GABAA) receptor, the main targets of sevoflurane, is excitatory rather than inhibitory in the immature neurons. The excitatory effects of the GABAA receptors have been linked to increased neuroapoptosis, elevated serum corticosterone levels and epigenetic modifications following neonatal sevoflurane exposure in rodents, which might contribute to sevoflurane-induced long-term cognitive abnormalities. We proposed that the excitatory GABAA receptor-mediated HPA axis activity might be a novel mechanism underlying sevoflurane-induced long-term cognitive impairments. More studies are needed to investigate the effectiveness and mechanisms by targeting the excitatory GABAA receptor as a prevention strategy to alleviate cognitive deficits induced by neonatal sevoflurane exposure in future.

中文翻译：

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GABAA 受体在新生儿七氟醚暴露引起的长期认知障碍中的作用

七氟醚是一种在儿科手术中广泛使用的吸入麻醉剂，被认为是相当安全且在停药后可逆的。然而，最近的临床前研究表明，围新生儿接触七氟醚可能会导致大脑发育异常。本综述旨在介绍和讨论实验室研究揭示的关于七氟醚对大脑发育的不良影响的累积实验数据。首先，我们总结了新生儿七氟醚暴露对认知功能的长期副作用。随后，我们介绍了在未成熟大脑中暴露于七氟醚后的结构变化，即神经细胞凋亡、神经发生和突触发生。最后，我们还讨论了晚年认知障碍的潜在机制，这是由新生儿七氟醚暴露引起的，并指出了减轻七氟醚引起的长期认知障碍的潜在策略。A型γ-氨基丁酸（GABA一种) 受体，七氟醚的主要靶标，在未成熟神经元中是兴奋性的而不是抑制性的。GABA的兴奋作用一种受体与啮齿动物新生儿七氟醚暴露后神经细胞凋亡增加、血清皮质酮水平升高和表观遗传修饰有关，这可能导致七氟醚诱导的长期认知异常。我们提出兴奋性 GABA一种受体介导的 HPA 轴活性可能是七氟醚诱导的长期认知障碍的一种新机制。需要更多的研究来研究针对兴奋性 GABA 的有效性和机制一种受体作为一种预防策略，以减轻未来新生儿七氟醚暴露引起的认知缺陷。