Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Neuroscience Research Institute, Zhengzhou University Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
CNS Neurosci Ther. 2024 Jan;30(1):e14554. doi: 10.1111/cns.14554. Epub 2023 Dec 17.
Sevoflurane is widely used for general anesthesia in children. Previous studies reported that multiple neonatal exposures to sevoflurane can induce long-term cognitive impairment in adolescent rats, but the underlying mechanisms were not defined.
Postnatal day 6 (P6) to P8 rat pups were exposed to 30% oxygen with or without 3% sevoflurane balanced with air. The Y maze test (YMT) and Morris water maze (MWM) tests were performed in some cohorts from age P35 to assess cognitive functions, and their brain samples were harvested at age P14, 21, 28, 35, and 42 for measurements of various molecular entities and in vivo electrophysiology experiments at age P35.
Sevoflurane exposure resulted in cognitive impairment that was associated with decreased synCAM1 expression in parvalbumin (PV) interneurons, a reduction of PV phenotype, disturbed gamma oscillations, and dendritic spine loss in the hippocampal CA3 region. Enriched environment (EE) increased synCAM1 expression in the PV interneurons and attenuated sevoflurane-induced cognitive impairment. The synCAM1 overexpression by the adeno-associated virus vector in the hippocampal CA3 region restored sevoflurane-induced cognitive impairment, PV phenotype loss, gamma oscillations decrease, and dendritic spine loss.
Our data suggested that neonatal sevoflurane exposure results in cognitive impairment through decreased synCAM1 expression in PV interneurons in the hippocampus.
七氟醚被广泛用于儿童全身麻醉。先前的研究报道，新生大鼠多次接触七氟醚可导致青少年期大鼠长期认知功能障碍，但潜在机制尚未明确。
将出生后第 6 天（P6）至第 8 天的幼鼠暴露于 30%氧气中，同时给予或不给予与空气平衡的 3%七氟醚。在一些队列中，从 P35 龄开始进行 Y 迷宫试验（YMT）和 Morris 水迷宫（MWM）试验，以评估认知功能，在 P14、21、28、35 和 42 龄时采集其脑组织样本，用于测量各种分子实体，并在 P35 龄时进行体内电生理实验。
七氟醚暴露导致认知功能障碍，与 PV 中间神经元中 synCAM1 表达减少、PV 表型减少、γ 振荡紊乱以及海马 CA3 区树突棘丢失有关。丰富环境（EE）增加了 PV 中间神经元中的 synCAM1 表达，并减轻了七氟醚诱导的认知障碍。通过腺相关病毒载体在海马 CA3 区过表达 synCAM1 可恢复七氟醚诱导的认知障碍、PV 表型丧失、γ 振荡减少和树突棘丢失。
我们的数据表明，新生期七氟醚暴露通过降低海马 PV 中间神经元中的 synCAM1 表达导致认知功能障碍。
