Wang Long-Rui, Zhao Zi-Yuan, Li Zhao-Wei, Jiang Yin-Ru, Sun Wen-Jing, Du Guan-Hua, Shi Rui-Li, Kong Ling-Lei
Beijing Key Laboratory of Innovative Drug Discovery and Polymorphic Druggability Research for Cerebrovascular Diseases, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.
Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, 030006, China.
Acta Pharmacol Sin. 2025 Oct 1. doi: 10.1038/s41401-025-01662-z.
Stroke is the second leading cause of mortality and the leading cause of adult disability worldwide. Neuroinflammation is a crucial mechanism that regulates the pathogenesis and prognosis of stroke and involves both peripheral and intracerebral immune cells. Neutrophils and microglia are the primary immune cells that mediate neuroinflammation and play bidirectional roles after stroke. Significant interactions between neutrophils and microglia exist. Microglia regulate the activation, infiltration, as well as formation of neutrophil extracellular traps (NETs), whereas neutrophils regulate the polarization and phagocytic activity of microglia. In this review, we summarize the bidirectional roles of neutrophils and microglia in stroke with an emphasis on the interactions between neutrophils and microglia, as well as the associated signaling pathways and targets involved. We further introduce potential stroke treatment drugs that regulate the interactions between neutrophils and microglia, including anti-inflammatory drugs and natural products. We propose that, according to the different ischemic times and cell activation states, regulating the interactions between neutrophils and microglia through relevant targets and signaling pathways may be an ideal strategy for the anti-inflammatory treatment of stroke, potentially improving treatment and prognosis of stroke. This review summarizes the bidirectional roles of neutrophils and microglia in stroke, respectively, focusing on the interactions and signaling pathways between neutrophils and microglia, as well as potential therapeutic targets and drugs.
