Huang Shiqian, Zhou Yuxi, Ji Haipeng, Zhang Tianhao, Liu Shiya, Ma Lulin, Deng Daling, Ding Yuanyuan, Han Linlin, Shu Shaofang, Wang Yu, Chen Xiangdong
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Avenue, Wuhan, 430022, China.
Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Respir Res. 2025 May 19;26(1):190. doi: 10.1186/s12931-025-03272-z.
The lung-brain axis represents a complex bidirectional communication network that is pivotal in the crosstalk between respiratory and neurological functions. This review summarizes the current understanding of the mechanisms and protein markers that mediate the effects of lung diseases on brain health.
In this review, we explore the mechanisms linking lung injury to neurocognitive impairments, focusing on neural pathways, immune regulation and inflammatory responses, microorganism pathways, and hypoxemia. Specifically, we highlight the role of the vagus nerve in modulating the central nervous system response to pulmonary stimuli; Additionally, the regulatory function of the immune system is underscored, with evidence suggesting that lung-derived immune mediators can traverse the blood-brain barrier, induce neuroinflammation and cognitive decline; Furthermore, we discuss the potential of lung microbiota to influence brain diseases through microbial translocation and immune activation; Finally, the impact of hypoxemia is examined, with findings indicating that it can exacerbate cerebral injury via oxidative stress and impaired perfusion. Moreover, we analyze how pulmonary conditions, such as pneumonia, ALI/ARDS, and asthma, contribute to neurological dysfunction. Prolonged mechanical ventilation can also contribute to cognitive impairment. Conversely, brain diseases (e.g., stroke, traumatic brain injury) can lead to acute respiratory complications. In addition, protein markers such as TLR4, ACE2, A-SAA, HMGB1, and TREM2 are crucial to the lung-brain axis and correlate with disease severity. We also discuss emerging therapeutic strategies targeting this axis, including immunomodulation and microbiome engineering. Overall, understanding the lung-brain interplay is crucial for developing integrated treatment strategies and improving patient outcomes. Further research is needed to elucidate the molecular mechanisms and foster interdisciplinary collaboration.
肺-脑轴代表一个复杂的双向通信网络，在呼吸和神经功能的相互作用中起关键作用。本综述总结了目前对介导肺部疾病对脑健康影响的机制和蛋白质标志物的理解。
在本综述中，我们探讨了将肺损伤与神经认知障碍联系起来的机制，重点关注神经通路、免疫调节和炎症反应、微生物通路以及低氧血症。具体而言，我们强调了迷走神经在调节中枢神经系统对肺部刺激反应中的作用；此外，免疫系统的调节功能也得到了强调，有证据表明肺源性免疫介质可以穿过血脑屏障，诱导神经炎症和认知衰退；此外，我们讨论了肺微生物群通过微生物易位和免疫激活影响脑部疾病的潜力；最后，研究了低氧血症的影响，结果表明它可通过氧化应激和灌注受损加剧脑损伤。此外，我们分析了肺炎、急性肺损伤/急性呼吸窘迫综合征和哮喘等肺部疾病如何导致神经功能障碍。长时间机械通气也可导致认知障碍。相反，脑部疾病（如中风、创伤性脑损伤）可导致急性呼吸并发症。此外，TLR4、ACE2、A-SAA、HMGB1和TREM2等蛋白质标志物对肺-脑轴至关重要，并与疾病严重程度相关。我们还讨论了针对该轴的新兴治疗策略，包括免疫调节和微生物组工程。总体而言，了解肺-脑相互作用对于制定综合治疗策略和改善患者预后至关重要。需要进一步研究以阐明分子机制并促进跨学科合作。
