Targeting the interactions between neutrophils and microglia: a novel strategy for anti-inflammatory treatment of stroke

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.