研究动态
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氧化铈纳米颗粒(nanoceria)预处理可减轻新生大鼠反复异氟醚麻醉导致的海马细胞死亡和认知功能障碍。

Cerium oxide nanoparticles (nanoceria) pretreatment attenuates cell death in the hippocampus and cognitive dysfunction due to repeated isoflurane anesthesia in newborn rats.

发表日期:2024 Aug 29
作者: Ezgi Kargi-Gemici, Aslıhan Şengelen, Yunus Aksüt, Onat Akyol, Selma Şengiz-Erhan, Mehmet Bay, Evren Önay-Uçar, Ayşin Selcan, Serdar Demirgan
来源: ANTIOXIDANTS & REDOX SIGNALING

摘要:

全身麻醉剂暴露,特别是长期或反复暴露,是神经损伤的一个重要原因。值得注意的是,用于儿科麻醉实践的异氟烷 (ISO) 对发育中的大脑有毒。早期的抗氧化系统相对较弱,需要抗氧化支持来保护大脑免受麻醉。氧化铈纳米粒子(CeO2-NPs、nanoceria)是纳米抗氧化剂,因其独特的表面化学、高稳定性和生物相容性而脱颖而出。尽管 CeO2-NPs 已被证明具有神经保护和认知功能促进作用,但尚无关于其对麻醉引起的神经毒性和认知障碍的保护作用的报道。在此,Wistar 白化大鼠幼仔在出生后 (P)7 P9 P11 天暴露于 ISO(1.5%,3 小时),并研究了 CeO2-NP 预处理(0.5mg/kg,腹膜内途径)的保护特性。第一次。对照组在 P7 9 11 接受 50% O2(3 小时)而不是 ISO。 ISO 前一小时暴露于纳米陶瓷可以保护发育中的大鼠大脑的海马神经元免受细胞凋亡[通过苏木精-伊红 (HE) 染色、使用 caspase-3 的免疫组织化学 (IHC) 分析以及使用 Bax/Bcl2、裂解的 caspase-3 进行免疫印迹来确定和 PARP1] 氧化应激和炎症 [通过使用 4-羟基壬烯醛 (4HNE)、核因子 kappa-B (NF-κB) 和肿瘤坏死因子-α (TNF-α) 进行免疫印迹测定]。 CeO2-NP 预处理还减少了莫里斯水迷宫评估的 ISO 诱导的学习(P28-32)和记忆(P33)缺陷。然而,在药物对照组中检测到记忆缺陷和趋触行为;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。总体而言,我们的研究结果支持使用纳米陶瓷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。版权所有 © 2024 Elsevier B.V. 保留所有权利。
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 (0.5mg/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.Copyright © 2024 Elsevier B.V. All rights reserved.