Abstract: Stroke, particularly ischemic stroke, induces dynamic interactions between peripheral monocytes and central nervous system cells, influencing neuroinflammation, repair, and functional recovery. Monocytes infiltrate the brain post-stroke and differentiate into macrophages, which interact with microglia, astrocytes, endothelial cells, and neurons. These interactions, mediated by chemokines, cytokines, and extracellular vesicles, can be detrimental or beneficial depending on context. Another interface is the gut–immune–brain axis, wherein gut microbiota, immune cells, and central nervous system-resident populations engage in reciprocal communication. Emerging therapies targeting monocyte subsets, their recruitment, and communication pathways. These include preconditioned peripheral blood mononuclear cells, bone marrow-derived mononuclear cells, mesenchymal stem cells, and cellfree or cell-mediated approaches utilizing the secretome. Together, these interventions hold promise for enhancing stroke recovery by modulating the immune–neural interface. This review summarizes recent advances in monocyte–central nervous system communication and its translational potential in stroke.

Key words: cell therapy, cell-cell communication, chemokines, cytokines, enteric microbiota, extracellular vesicles, macrophage, monocytes, mononuclear cell, peripheral blood mononuclear cells