Gui-Nan Jiang, Qiu-Yue Lin, Xiang-Bo An, Wei-Jia Yu, Jie Bai, Xin Yu, Feng Wang, Hui-Hua Li
{"title":"Integrin CD11b Alleviates Cerebral Ischemia/Reperfusion Injury via a Mechanism Involving Microglia/Macrophage Polarization","authors":"Gui-Nan Jiang, Qiu-Yue Lin, Xiang-Bo An, Wei-Jia Yu, Jie Bai, Xin Yu, Feng Wang, Hui-Hua Li","doi":"10.1007/s12031-025-02414-8","DOIUrl":null,"url":null,"abstract":"<div><p>The polarization of microglia/macrophages is crucial for maintaining the neuroinflammatory response during cerebral ischemia/reperfusion (I/R) injury. Integrin CD11b is implicated in the processes of neuroinflammation, immune regulation, and nerve injury repair. However, its role in microglia- and macrophage-mediated neuroinflammation during cerebral I/R injury remains poorly understood. Wild-type (WT), CD11b knockout (KO), or neutralizing antibody-treated mice were subjected to a transient cerebral artery I/R injury (tMCAO) model. CD11b expression was detected by qPCR, immunofluorescence, and western blotting. Histopathological features were evaluated by H&E and Nissl staining, ROS production was detected by DHE staining, neuronal apoptosis was detected by TUNEL assays, and microglia polarization was evaluated by immunofluorescence staining. We discovered that CD11b was significantly increased in the ischemic penumbra following tMCAO. CD11b KO significantly alleviated tMCAO-induced infarct, neurological deficits, oxidative stress, and neuronal apoptosis in the ischemic penumbra. Moreover, CD11b KO significantly enhanced the anti-inflammatory phenotype transition of microglia/macrophages, leading to accelerated inflammation resolution. Furthermore, pharmacological blockade of CD11b demonstrated a protective effect similar to that of CD11b KO. Meanwhile, CD11b deficiency significantly inhibited the activation of p-p65/p-STAT1 signaling pathway and upregulated p-STAT6 expression. In conclusion, CD11b protects against cerebral I/R injury by modulating microglial and macrophage polarization, thereby reducing subsequent neuroinflammation and neuronal death. Our findings suggest that CD11b intervention could be a potential therapeutic strategy for acute cerebral ischemic stroke.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s12031-025-02414-8","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The polarization of microglia/macrophages is crucial for maintaining the neuroinflammatory response during cerebral ischemia/reperfusion (I/R) injury. Integrin CD11b is implicated in the processes of neuroinflammation, immune regulation, and nerve injury repair. However, its role in microglia- and macrophage-mediated neuroinflammation during cerebral I/R injury remains poorly understood. Wild-type (WT), CD11b knockout (KO), or neutralizing antibody-treated mice were subjected to a transient cerebral artery I/R injury (tMCAO) model. CD11b expression was detected by qPCR, immunofluorescence, and western blotting. Histopathological features were evaluated by H&E and Nissl staining, ROS production was detected by DHE staining, neuronal apoptosis was detected by TUNEL assays, and microglia polarization was evaluated by immunofluorescence staining. We discovered that CD11b was significantly increased in the ischemic penumbra following tMCAO. CD11b KO significantly alleviated tMCAO-induced infarct, neurological deficits, oxidative stress, and neuronal apoptosis in the ischemic penumbra. Moreover, CD11b KO significantly enhanced the anti-inflammatory phenotype transition of microglia/macrophages, leading to accelerated inflammation resolution. Furthermore, pharmacological blockade of CD11b demonstrated a protective effect similar to that of CD11b KO. Meanwhile, CD11b deficiency significantly inhibited the activation of p-p65/p-STAT1 signaling pathway and upregulated p-STAT6 expression. In conclusion, CD11b protects against cerebral I/R injury by modulating microglial and macrophage polarization, thereby reducing subsequent neuroinflammation and neuronal death. Our findings suggest that CD11b intervention could be a potential therapeutic strategy for acute cerebral ischemic stroke.
期刊介绍:
The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.