Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China and Sichuan Provincial Women's and Children's Hospital, Chengdu, China.
Department of Operating Room Nursing, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Neurotox Res. 2022 Oct;40(5):1405-1414. doi: 10.1007/s12640-022-00529-z. Epub 2022 Aug 2.
Sevoflurane anesthesia during neonatal period was reported to sensitize the rodent animals to stress later in life. The authors tested the hypothesis that repeated sevoflurane exposures in neonatal rats increased the brain vulnerability to future stress exposure and resulted in fear extinction deficit and investigated whether the neonatal brain depolarizing γ-aminobutyric acid type A receptor (GABAR) is involved in mediating these abnormalities. Neonatal Sprague-Dawley male rats, pretreated with vehicle or the NKCC1 inhibitor, bumetanide, received sequential exposures to 3% sevoflurane for 2 h on postnatal days (P) 5, P6, and P7 and then were exposed to electric foot shock stress in fear conditioning training at P14. Juvenile rats at different developmental brain stage receiving identical sevoflurane exposures on P25, P26, and P27 were also studied. The results showed repeated sevoflurane exposures in neonatal rats and increased the cation-chloride cotransporters NKCC1/KCC2 ratio in the PFC at P14. Repeated exposures to sevoflurane in neonatal rather than juvenile rats enhanced the stress response and exacerbated neuroapoptosis in the PFC after exposed to electric foot shock in fear conditioning training. Neonatal rather than juvenile sevoflurane-exposed rats exhibited deficits in fear extinction training and recall. Pretreatment of neonatal rats prior to sevoflurane exposures with bumetanide reduced the NKCC1/KCC2 ratio at P14 and ameliorated most of the subsequent adverse effects. Our study indicates that repeated sevoflurane exposures in neonatal rats might increase the brain vulnerability to future stress exposure and resulted in fear extinction deficit, which might be associated with the neonatal enhanced brain depolarizing GABAR activity.
有报道称，新生儿期的七氟醚麻醉会使啮齿动物在以后的生活中对压力敏感。作者测试了以下假设：在新生大鼠中重复七氟醚暴露会增加大脑对未来应激暴露的脆弱性，并导致恐惧消退缺陷，并研究了新生儿大脑去极化γ-氨基丁酸 A 型受体 (GABAR) 是否参与介导这些异常。预处理用载体或 NKCC1 抑制剂布美他尼的新生 Sprague-Dawley 雄性大鼠，在出生后第 5、6 和 7 天接受 3%七氟醚 2 小时的连续暴露，然后在 P14 进行电足底应激恐惧条件反射训练。在 P25、P26 和 P27 接受相同七氟醚暴露的不同发育阶段的幼年大鼠也进行了研究。结果表明，新生大鼠重复七氟醚暴露会增加 P14 时 PFC 中的阳离子-氯离子共转运蛋白 NKCC1/KCC2 比值。与幼年大鼠相比，在新生大鼠中重复暴露于七氟醚会增强应激反应，并在恐惧条件反射训练中暴露于电足底应激后加剧 PFC 中的神经细胞凋亡。与幼年大鼠相比，在七氟醚暴露的新生大鼠中进行恐惧消退训练和回忆时表现出缺陷。在七氟醚暴露前用布美他尼预处理新生大鼠可降低 P14 时的 NKCC1/KCC2 比值，并改善随后的大部分不良影响。我们的研究表明，新生大鼠中重复的七氟醚暴露可能会增加大脑对未来应激暴露的脆弱性，并导致恐惧消退缺陷，这可能与新生儿增强的大脑去极化 GABAR 活性有关。
