Abstract：
Central nervous system oxygen toxicity (CNS-OT) is a complication of hyperbaric oxygen (HBO) treatment, with limited prevention and treatment options available. In this study, we aimed to explore the effect of polyethylene glycol 300 (PEG300) on CNS-OT and underlying mechanisms. Motor and cognitive functions of mice in normobaric conditions were evaluated by Morris water maze, passive active avoidance, and rotarod tests. HBO was applied at 6 atmospheres absolute (ATA) for 30 min after drug administration. The latency period of convulsion in mice was recorded, and hippocampal tissues were extracted for biochemical experiments. Our experimental results showed that PEG300 extended the convulsion latencies in CNS-OT mice, reduced oxidative stress and inflammation levels in hippocampal tissues. Furthermore, PEG300 preserved mitochondrial integrity and maintained mitochondrial membrane potential in hippocampal tissue by upregulating Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (PGC-1α). This protective effect was enhanced following the administration of ZLN005, an agonist of PGC-1a. Hence, our study suggests that PEG300 might exert protective effects by upregulating PGC-1α expression and preserving mitochondrial health, offering promising prospects for CNS-OT treatment.
摘要：
中枢神经系统氧中毒（CNS-OT）是高压氧（HBO）治疗的并发症，有限的预防和治疗选择。在这项研究中,我们旨在探讨聚乙二醇300（PEG300）对CNS-OT的影响及其潜在机制。通过Morris水迷宫评估了正常压力条件下小鼠的运动和认知功能，被动主动回避,和旋转杆测试。在给药后以6个绝对大气压(ATA)施用HBO30分钟。记录小鼠惊厥的潜伏期，提取海马组织进行生化实验。我们的实验结果表明，PEG300延长了CNS-OT小鼠的惊厥潜伏期，降低海马组织的氧化应激和炎症水平。此外，PEG300通过上调过氧化物酶体增殖物激活的受体γ-共激活因子1-α(PGC-1α)保持线粒体完整性并维持海马组织的线粒体膜电位。在施用PGC-1a的激动剂ZLN005后,这种保护作用得到增强。因此，我们的研究表明，PEG300可能通过上调PGC-1α表达和保持线粒体健康而发挥保护作用，为CNS-OT治疗提供了有希望的前景。
