Fu Ningning, Wang Yangyang, Zhu Ruilou, Li Ningning, Zeng Shuang, Miao Mengrong, Yang Yitian, Sun Mingyang, Zhang Jiaqiang
Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, P.R. China.
Academy of Medical Sciences of Zhengzhou University, Zhengzhou, Henan 450001, China.
ACS Chem Neurosci. 2023 Mar 15;14(6):1146-1155. doi: 10.1021/acschemneuro.2c00764. Epub 2023 Feb 21.
Sevoflurane (Sevo) is one of the most commonly used general anesthetics for infants and young children. We investigated whether Sevo impairs neurological functions, myelination, and cognition via the γ-aminobutyric acid A receptor (GABAR) and Na-K-2Cl cotransporter (NKCC1) in neonatal mice. On postnatal days 5-7, mice were exposed to 3% Sevo for 2 h. On postnatal day 14, mouse brains were dissected, and oligodendrocyte precursor cell line level lentivirus knockdown of GABRB3, immunofluorescence, and transwell migration assays were performed. Finally, behavioral tests were conducted. Multiple Sevo exposure groups exhibited increased neuronal apoptosis levels and decreased neurofilament protein levels in the mouse cortex compared with the control group. Sevo exposure inhibited the proliferation, differentiation, and migration of the oligodendrocyte precursor cells, thereby affecting their maturation process. Electron microscopy revealed that Sevo exposure reduced myelin sheath thickness. The behavioral tests showed that multiple Sevo exposures induced cognitive impairment. GABAR and NKCC1 inhibition provided protection against Sevo-induced neurotoxicity and cognitive dysfunction. Thus, bicuculline and bumetanide can protect against Sevo-induced neuronal injury, myelination impairment, and cognitive dysfunction in neonatal mice. Furthermore, GABAR and NKCC1 may be mediators of Sevo-induced myelination impairment and cognitive dysfunction.
七氟醚（Sevo）是婴幼儿最常用的全身麻醉剂之一。我们研究了七氟醚是否通过新生小鼠的γ-氨基丁酸A受体（GABAR）和钠-钾-2氯协同转运蛋白（NKCC1）损害神经功能、髓鞘形成和认知。在出生后第5至7天，将小鼠暴露于3%的七氟醚中2小时。在出生后第14天，解剖小鼠大脑，并进行少突胶质前体细胞系水平的慢病毒敲低GABRB3、免疫荧光和transwell迁移试验。最后，进行行为测试。与对照组相比，多次七氟醚暴露组小鼠皮层的神经元凋亡水平增加，神经丝蛋白水平降低。七氟醚暴露抑制了少突胶质前体细胞的增殖、分化和迁移，从而影响其成熟过程。电子显微镜显示，七氟醚暴露降低了髓鞘厚度。行为测试表明，多次七氟醚暴露会导致认知障碍。GABAR和NKCC1抑制可预防七氟醚诱导的神经毒性和认知功能障碍。因此，荷包牡丹碱和布美他尼可预防七氟醚诱导的新生小鼠神经元损伤、髓鞘形成障碍和认知功能障碍。此外，GABAR和NKCC1可能是七氟醚诱导的髓鞘形成障碍和认知功能障碍的介质。
