Selective modulation of microglia polarization to M2 phenotype for stroke treatment

• Microglia play a dual role in ischemic stroke.
• In ischemic stroke, microglia show transient neuroprotective M2 phenotype followed by a shift to destructive M1 phenotype.
• Multi-signal pathways regulating the alternation of microglial phenotype are reviewed.
• Selective modulation of microglia polarization to M2 phenotype may be a possible therapeutic target for ischemic stroke.

Resident microglia are the major immune cells in the brain, acting as the first defense of the central nervous system. Following cerebral ischemia, microglia respond to this injury at first and transform from surveying microglia to active state. The activated microglia play a dual role in the ischemic injury, due to distinct microglia phenotypes, including deleterious M1 and neuroprotective M2. However, microglia show transient M2 phenotype followed by a shift to M1. The high ratio of M1 to M2 is significantly related to ischemic injury. Many signal pathways participate in the alternation of microglial phenotype, presenting potential therapeutic targets for selectively modulating M2 polarization of microglia. In this review, we discuss how the M2 phenotype mediates neuroprotective effects and summarize the alternation of signaling cascades that control microglial phenotype after ischemic stroke.