Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Key Laboratory of Anesthesia and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei 230022, China.
CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Science at the Microscale, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei 230026, China.
Biomaterials. 2025 Jan;312:122744. doi: 10.1016/j.biomaterials.2024.122744. Epub 2024 Aug 5.
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.
中枢神经系统（CNS）内的炎症可能由手术创伤引发，被认为是导致术后认知功能障碍（POCD）的重要因素。减轻外周手术部位炎症与减轻 CNS 炎症反应、从而缓解 POCD 症状之间的关系仍不确定。值得注意的是，一氧化碳（CO）作为一种气体递质，具有显著的抗炎作用。在此，我们开发了一种一氧化碳释放胶束（CORMs），这是一种纳米颗粒，在暴露于 650nm 光照射时可安全且局部释放 CO。在 POCD 小鼠模型中，用光激活的 CORMs（CORMs+hv）治疗显著降低了外周血和海马体中白细胞介素（IL）-6、IL-1β 和肿瘤坏死因子-α（TNF-α）的浓度，同时减少了海马 CA1 区的钙结合接头蛋白 1 的离子化。此外，CORMs+hv 治疗减少了 Evans 蓝外渗，增加了紧密连接蛋白 zonula occludens-1 和 occludin 的表达，增强了神经认知功能，并促进了骨折愈合。生物信息学分析和实验验证确定 Htr1b 和 Trhr 是与 POCD 相关的神经活性配体-受体相互作用信号通路中的潜在关键调节因子。这项工作为驱动 POCD 的机制和治疗干预途径提供了新的视角。
