Abstract：
Inflammation within the central nervous system (CNS), which may be triggered by surgical trauma, has been implicated as a significant factor contributing to postoperative cognitive dysfunction (POCD). The relationship between mitigating inflammation at peripheral surgical sites and its potential to attenuate the CNS inflammatory response, thereby easing POCD symptoms, remains uncertain. Notably, carbon monoxide (CO), a gasotransmitter, exhibits pronounced anti-inflammatory effects. Herein, we have developed carbon monoxide-releasing micelles (CORMs), a nanoparticle that safely and locally liberates CO upon exposure to 650 nm light irradiation. In a POCD mouse model, treatment with CORMs activated by light (CORMs + hv) markedly reduced the concentrations of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-α) in both the peripheral blood and the hippocampus, alongside a decrease in ionized calcium-binding adapter molecule 1 in the hippocampal CA1 region. Furthermore, CORMs + hv treatment diminished Evans blue extravasation, augmented the expression of tight junction proteins zonula occludens-1 and occludin, enhanced neurocognitive functions, and fostered fracture healing. Bioinformatics analysis and experimental validation has identified Htr1b and Trhr as potential key regulators in the neuroactive ligand-receptor interaction signaling pathway implicated in POCD. This work offers new perspectives on the mechanisms driving POCD and avenues for therapeutic intervention.
摘要：
中枢神经系统（CNS）内的炎症，这可能是由手术创伤引发的，已被认为是导致术后认知功能障碍（POCD）的重要因素。减轻外周手术部位的炎症与减轻中枢神经系统炎症反应的潜力之间的关系，从而缓解POCD症状，仍然不确定。值得注意的是,一氧化碳(CO),一个气体发射器,表现出明显的抗炎作用。在这里，我们已经开发了释放一氧化碳的胶束（CORM），一种纳米粒子，在暴露于650nm的光照射时安全和局部释放CO。在POCD小鼠模型中，光激活的CORM治疗（CORM+hv）显着降低了白细胞介素（IL）-6，IL-1β的浓度，和肿瘤坏死因子-α（TNF-α）在外周血和海马，伴随着海马CA1区离子化钙结合衔接分子1的减少。此外，CORM+hv治疗减少了伊文思蓝外渗，增强紧密连接蛋白小带闭塞蛋白1和闭塞蛋白的表达，增强神经认知功能，促进骨折愈合。生物信息学分析和实验验证已将Htr1b和Trhr确定为与POCD有关的神经活性配体-受体相互作用信号通路的潜在关键调节剂。这项工作为推动POCD的机制和治疗干预的途径提供了新的视角。
