全身麻醉药暴露,特别是长时间或反复暴露,是神经损伤的重要原因.值得注意的是,异氟烷(ISO),用于儿科麻醉实践,对发育中的大脑有毒。早期相对较弱的抗氧化系统需要抗氧化支持来保护大脑免受麻醉。氧化铈纳米颗粒(CeO2-NP,nanoceria)是纳米抗氧化剂,由于其独特的表面化学而脱颖而出,高稳定性,和生物相容性。尽管CeO2-NP已被证明具有神经保护和认知功能促进作用,没有关于它们对麻醉诱导的神经毒性和认知障碍的保护作用的报道。在这里,Wistar白化病幼鼠暴露于ISO(1.5%,3-h)在出生后第(P)7+P9+P11天,以及CeO2-NP预处理的保护特性(0.5mg/kg,腹膜内途径)进行了首次调查。在P7+9+11的对照组接受50%O2(3-h)而不是ISO。在ISO保护发育中的大鼠大脑的海马神经元抵抗凋亡前一小时暴露于纳米二氧化铈[通过苏木精-伊红(HE)染色测定,使用caspase-3进行免疫组织化学(IHC)分析,并使用Bax/Bcl2,裂解的caspase-3和PARP1]氧化应激进行免疫印迹,和炎症[通过用4-羟基壬烯醛(4HNE)免疫印迹确定,核因子κB(NF-κB),和肿瘤坏死因子-α(TNF-α)]。CeO2-NP预处理还减少了由Morris水迷宫评估的ISO诱导的学习(在P28-32)和记忆(在P33)缺陷。然而,在药物对照组中检测到记忆缺陷和thigmotic行为;通过剂量研究可以消除这些有害影响,从而提供支持更安全使用的证据。总的来说,我们的研究结果支持使用纳米二氧化硅进行预处理作为一种简单的策略,可用于儿科麻醉实践,以保护婴儿和儿童免受ISO诱导的细胞死亡以及学习和记忆缺陷的影响.
General anesthetics exposure, particularly prolonged or repeated exposure, is a crucial cause of neurological injuries. Notably, isoflurane (ISO), used in pediatric anesthesia practice, is toxic to the developing brain. The relatively weak antioxidant system at early ages needs antioxidant support to protect the brain against anesthesia. Cerium oxide nanoparticles (CeO2-NPs, nanoceria) are nano-antioxidants and stand out due to their unique surface chemistry, high stability, and biocompatibility. Although CeO2-NPs have been shown to exhibit neuroprotective and cognitive function-facilitating effects, there are no reports on their protective effects against anesthesia-induced neurotoxicity and cognitive impairments. Herein, Wistar albino rat pups were exposed to ISO (1.5 %, 3-h) at postnatal day (P)7+P9+P11, and the protective properties of CeO2-NP pretreatment (0.5 mg/kg, intraperitoneal route) were investigated for the first time. The control group at P7+9+11 received 50 % O2 (3-h) instead of ISO. Exposure to nanoceria one-hour before ISO protected hippocampal neurons of the developing rat brain against apoptosis [determined by hematoxylin-eosin (HE) staining, immunohistochemistry (IHC) analysis with caspase-3, and immunoblotting with Bax/Bcl2, cleaved caspase-3 and PARP1] oxidative stress, and inflammation [determined by immunoblotting with 4-hydroxynonenal (4HNE), nuclear factor kappa-B (NF-κB), and tumor necrosis factor-alpha (TNF-α)]. CeO2-NP pretreatment also reduced ISO-induced learning (at P28-32) and memory (at P33) deficits evaluated by Morris Water Maze. However, memory deficits and thigmotactic behaviors were detected in the agent-control group; elimination of these harmful effects will be possible with dose studies, thus providing evidence supporting safer use. Overall, our findings support pretreatment with nanoceria application as a simple strategy that might be used for pediatric anesthesia practice to protect infants and children from ISO-induced cell death and learning and memory deficits.