Cigarette Smoke-Induced COPD Exacerbates Postoperative Cognitive Impairment via Hippocampal Neuroinflammation: A Dual-Hit Rat Model

<title>Abstract</title> <p>Chronic obstructive pulmonary disease (COPD) is often associated with cognitive dysfunction, which may worsen during the recovery from bone fractures. This study aims to investigate the impact of chronic cigarette smoke-induced COPD on cognitive function following right tibial fracture in rats, filling an important gap in the current literature. We established a COPD model through chronic cigarette smoke exposure, followed by surgical intervention for right tibial fracture, and assessed cognitive function using behavioral tests such as the Morris water maze. Our results indicate that COPD rats exhibited significant cognitive decline after right tibial fracture, while the expression of NLRP3 inflammasome components, reactive oxygen species (ROS), and pro-inflammatory cytokines in the hippocampal tissue was significantly elevated, suggesting a additive effect between COPD and fractures on cognitive decline. Furthermore, changes in apoptosis and autophagy-related proteins further elucidated the potential molecular mechanisms. Our findings emphasize that the combined effects of COPD and tibial fractures exacerbate cognitive dysfunction, indicating possible therapeutic targets for cognitive impairment in the context of chronic diseases. Future research should explore intervention strategies targeting inflammation and oxidative stress to improve cognitive outcomes in COPD patients.</p>