Ischemic stroke causes rapid cellular distress and death in the central nervous system, leading its resident cells to disseminate diffusible inflammatory signals that can reach immune cells in distant peripheral tissues. Monocytes respond quickly to this distress signal and are among the earliest peripheral immune cell types to infiltrate the ischemic brain, where they differentiate into macrophages and critically contribute to brain injury and repair. Monocyte-derived macrophages (MDM) can be recruited from several different reservoirs throughout the body, and their phenotypes may differ by their origin and/or route of invasion. The objective of this review is to examine the roles of MDM in diverse processes that occur in a stroke injury, including phagocytosis, blood-brain barrier stabilization, inflammatory signal propagation and resolution, white matter repair, angiogenesis, and neurogenesis. We also describe how monocytes are mobilized in human patients and animal models of stroke, and their transformation into MDM. Although ischemic stroke therapies are currently limited to restoring blood flow, new strategies harnessing the CNS-invading and reparatory power of MDM are on the horizon. Hence, a better understanding of the molecular mechanisms that promote beneficial properties of MDM may optimize macrophage-targeting therapies for stroke in the future.
Dufort et al. (Thu,) studied this question.