Abstract：
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 (GABAAR) 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. GABAAR 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, GABAAR and NKCC1 may be mediators of Sevo-induced myelination impairment and cognitive dysfunction.
摘要：
七氟醚（Sevo）是婴幼儿最常用的全身麻醉药之一。我们调查了Sevo是否损害神经功能，髓鞘形成,和通过γ-氨基丁酸A受体（GABAAR）和Na-K-2Cl-协同转运蛋白（NKCC1）在新生小鼠中的认知。在出生后第5-7天，将小鼠暴露于3％Sevo2小时。在出生后第14天，解剖小鼠大脑，和少突胶质细胞前体细胞水平慢病毒敲低GABRB3，免疫荧光，并进行了transwell迁移测定。最后,进行了行为测试。与对照组相比，多个Sevo暴露组表现出小鼠皮质中神经元凋亡水平升高和神经丝蛋白水平降低。Sevo暴露抑制了增殖，分化,少突胶质细胞前体细胞的迁移，从而影响其成熟过程。电子显微镜显示，Sevo暴露减少了髓鞘的厚度。行为测试表明，多次Sevo暴露会导致认知障碍。GABAAR和NKCC1抑制提供了针对Sevo诱导的神经毒性和认知功能障碍的保护作用。因此，bicuculline和bumetanide可以防止Sevo诱导的神经元损伤，髓鞘形成损伤,和新生小鼠的认知功能障碍。此外，GABAAR和NKCC1可能是Sevo诱导的髓鞘形成障碍和认知功能障碍的介质。
