Figure 2.

Schematic of how the FPR agonist AnxA1 could reduce inflammation in the brain following I/R injury and exert neuroprotection. Neutrophils are activated after I/R injury. They roll, adhere and migrate into the tissue. AnxA1 is released from neutrophil cytosolic granules to the cell surface, where it interacts with FPRs in an autocrine or paracrine fashion. Administration of AnxA1 (or the N-terminal peptide Ac2–26) causes the leukocyte detachment from endothelial cells. Resident cells, such as microglia, are also activated by I/R injury and, like blood-borne cells, release a plethora of damaging mediators such as reactive oxygen species, cytokines (TNF-α, IL-1β) and leukotrienes. The involvement of AnxA1 in these processes might be similar to that observed in the peripheral microvasculature, namely to promote resolution. The receptors that mediate this process in stroke remain unknown, although evidence suggests that FPR/ALX plays a role.