Microglial and macrophage polarization—new prospects for brain repair

After brain injuries, microglia and macrophages can aid or hinder tissue repair depending on polarization toward specific cell phenotypes. This Perspectives article describes the phenotypic dynamics and different functions of these cells after acute CNS injury and argues that therapeutic approaches should focus on subtle adjustment of the balance between their phenotypes. The traditional view of the adult brain as a static organ has changed in the past three decades, with the emergence of evidence that it remains plastic and has some regenerative capacity after injury. In the injured brain, microglia and macrophages clear cellular debris and orchestrate neuronal restorative processes. However, activation of these cells can also hinder CNS repair and expand tissue damage. Polarization of macrophage populations toward different phenotypes at different stages of injury might account for this dual role. This Perspectives article highlights the specific roles of polarized microglial and macrophage populations in CNS repair after acute injury, and argues that therapeutic approaches targeting cerebral inflammation should shift from broad suppression of microglia and macrophages towards subtle adjustment of the balance between their phenotypes. Breakthroughs in the identification of regulatory molecules that control these phenotypic shifts could ultimately accelerate research towards curing brain disorders.