Cao Tianyu, Jiang Sufang, Wang Xueji, Huang Peiying, Zhou Lijie, Di Lichao, Han Shuang, Huang Lining
Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Department of Anesthesiology, The First Hospital of Qinhuangdao, Qinhuangdao, Hebei, China.
Mol Neurobiol. 2025 Feb;62(2):2348-2361. doi: 10.1007/s12035-024-04413-z. Epub 2024 Aug 6.
Sevoflurane is one of the most commonly used general anesthetics for children and infants. Recent research indicates that repeated exposure to sevoflurane in neonates induces cognitive and fine motor deficits. Peroxisome proliferator-activated receptor-γ (PPARγ) agonists have garnered significant attention as potential therapies for a variety of neurological conditions. In this research, we evaluated whether pretreatment with rosiglitazone in neonatal mice could address myelination defects, cognitive impairment, and fine motor dysfunction via PPARγ. The mice were exposed to 3% sevoflurane for 2 h on postnatal days 6-8 (P6-P8). Behavioral tests were conducted from P29 to P34. Additionally, we evaluated morphological and functional changes related to myelin. Our results showed that rosiglitazone pretreatment significantly ameliorated the cognitive and fine motor impairments of repeated neonatal sevoflurane exposure. In addition, rosiglitazone pretreatment promoted oligodendrocyte precursor cells (OPCs) differentiation and myelination. This suggests that rosiglitazone may be used in clinical settings to enhance the security of neonatal sevoflurane exposure. Furthermore, PPARγ and fatty acid synthase (FASN) may be mediators for rosiglitazone, which alleviates myelination defects, cognitive impairment, and fine motor dysfunction.
七氟醚是儿童和婴儿最常用的全身麻醉剂之一。最近的研究表明，新生儿反复接触七氟醚会导致认知和精细运动功能缺陷。过氧化物酶体增殖物激活受体γ（PPARγ）激动剂作为多种神经系统疾病的潜在治疗方法已受到广泛关注。在本研究中，我们评估了在新生小鼠中用罗格列酮预处理是否可以通过PPARγ解决髓鞘形成缺陷、认知障碍和精细运动功能障碍。在出生后第6 - 8天（P6 - P8），将小鼠暴露于3%的七氟醚中2小时。在P29至P34进行行为测试。此外，我们评估了与髓鞘相关的形态和功能变化。我们的结果表明，罗格列酮预处理显著改善了新生儿反复暴露于七氟醚后的认知和精细运动损伤。此外，罗格列酮预处理促进了少突胶质前体细胞（OPC）的分化和髓鞘形成。这表明罗格列酮可用于临床环境中，以提高新生儿七氟醚暴露的安全性。此外，PPARγ和脂肪酸合酶（FASN）可能是罗格列酮的介导因子，其可减轻髓鞘形成缺陷、认知障碍和精细运动功能障碍。
