Xu Feng-Hua, Sun Xiao, Zhu Jun, Kong Ling-Yang, Chang Yuan, Li Ning, Hui Wen-Xiang, Zhang Cong-Peng, Cheng Yi-Ming, Han Wen-Xin, Tian Zhi-Min, Qiao Yan-Ning, Chen Dong-Feng, Liu Lei, Feng Da-Yun, Han Jing
Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xi'an, China.
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, China.
Front Cell Infect Microbiol. 2025 Mar 4;14:1413018. doi: 10.3389/fcimb.2024.1413018. eCollection 2024.
Recent research has made significant progress in elucidating gastrointestinal complications following acute cerebral infarction (ACI), which includes disorders in intestinal motility and dysbiosis of the gut microbiota. Nevertheless, the role of the gut (which is acknowledged as being the largest immune organ) in the immunoreactive effects of polydopamine nanoparticles (PDA) on acute ischemic stroke remains inadequately understood. In addition to its function in nutrient absorption, the gut acts as a protective barrier against microbes. Systemic immune responses, which are triggered by the disruption of gut barrier integrity, are considered as one of the mechanisms underlying acute ischemic stroke, with the gut-brain axis (GBA) playing a pivotal role in this process.
In this study, we used a PDA intervention in an ACI model to investigate ACI-like behavior, intestinal barrier function, central and peripheral inflammation, and hippocampal neuron excitability, thus aiming to elucidate the mechanisms through which PDA improves ACI via the GBA.
Our findings indicated that as ACI mice experienced dysbiosis of the gut microbiota and intestinal barrier damage, the levels of proinflammatory factors in the serum and brain significantly increased. Additionally, the activation of astrocytes in the hippocampal region and neuronal apoptosis were observed in ACI mice. Importantly, our study is the first to provide evidence demonstrating that PDA effectively suppresses the neuroimmune interactions of the gut-brain axis and significantly improves intestinal epithelial barrier integrity.
We hope that our discoveries will serve as a foundation for further explorations of the therapeutic mechanisms of PDA in ACI, particularly in elucidating the protective roles of gut microbiota and intestinal barrier function, as well as in the development of more targeted clinical interventions for ACI.
近期研究在阐明急性脑梗死（ACI）后的胃肠道并发症方面取得了重大进展，其中包括肠道动力障碍和肠道微生物群失调。然而，肠道（被认为是最大的免疫器官）在聚多巴胺纳米颗粒（PDA）对急性缺血性中风的免疫反应作用方面仍未得到充分了解。除了在营养吸收方面的功能外，肠道还作为抵御微生物的保护屏障。肠道屏障完整性破坏引发的全身免疫反应被认为是急性缺血性中风的潜在机制之一，而肠-脑轴（GBA）在此过程中起关键作用。
在本研究中，我们在ACI模型中使用PDA干预，以研究ACI样行为、肠道屏障功能、中枢和外周炎症以及海马神经元兴奋性，从而旨在阐明PDA通过GBA改善ACI的机制。
我们的研究结果表明，随着ACI小鼠出现肠道微生物群失调和肠道屏障损伤，血清和脑中的促炎因子水平显著升高。此外，在ACI小鼠中观察到海马区星形胶质细胞的激活和神经元凋亡。重要的是，我们的研究首次提供证据表明，PDA有效抑制肠-脑轴的神经免疫相互作用，并显著改善肠道上皮屏障完整性。
我们希望我们的发现将为进一步探索PDA在ACI中的治疗机制奠定基础，特别是在阐明肠道微生物群和肠道屏障功能的保护作用以及开发更具针对性的ACI临床干预措施方面。
