Jiang Gui-Nan, Lin Qiu-Yue, An Xiang-Bo, Yu Wei-Jia, Bai Jie, Yu Xin, Wang Feng, Li Hui-Hua
First Affiliated Hospital of Dalian Medical University, Department of Interventional Therapy, No.222 Zhongshan Road, Dalian, 116011, China.
First Affiliated Hospital of Dalian Medical University, Institute of Cardiovascular Diseases, No.193 Lianhe Road, Dalian, 116011, China.
J Mol Neurosci. 2025 Sep 20;75(4):120. doi: 10.1007/s12031-025-02414-8.
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.
小胶质细胞/巨噬细胞的极化对于在脑缺血/再灌注（I/R）损伤期间维持神经炎症反应至关重要。整合素CD11b参与神经炎症、免疫调节和神经损伤修复过程。然而，其在脑I/R损伤期间小胶质细胞和巨噬细胞介导的神经炎症中的作用仍知之甚少。对野生型（WT）、CD11b基因敲除（KO）或用中和抗体处理的小鼠进行短暂性脑动脉I/R损伤（tMCAO）模型实验。通过qPCR、免疫荧光和蛋白质免疫印迹法检测CD11b的表达。通过苏木精-伊红（H&E）染色和尼氏染色评估组织病理学特征，通过二氢乙锭（DHE）染色检测活性氧（ROS）生成，通过末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）法检测神经元凋亡，并通过免疫荧光染色评估小胶质细胞极化。我们发现，tMCAO后缺血半暗带中CD11b显著增加。CD11b基因敲除显著减轻了tMCAO诱导的梗死、神经功能缺损、氧化应激以及缺血半暗带中的神经元凋亡。此外，CD11b基因敲除显著增强了小胶质细胞/巨噬细胞的抗炎表型转变，从而加速了炎症消退。此外，对CD11b的药物性阻断显示出与CD11b基因敲除相似的保护作用。同时，CD11b缺乏显著抑制了p-p65/p-STAT1信号通路的激活并上调了p-STAT6的表达。总之，CD11b通过调节小胶质细胞和巨噬细胞极化来保护脑免受I/R损伤，从而减少随后的神经炎症和神经元死亡。我们的研究结果表明，CD11b干预可能是急性脑缺血性中风的一种潜在治疗策略。
