Microglia in health and CNS disease: Learning from animal models

Microglia are the resident macrophage in the central nervous system (CNS) and are essential for maintaining homeostatic functions of the CNS. During development, the proliferation, and colonization of yolk sac-derived progenitors in the CNS are precisely regulated by a specific set of genes. Microglia also play a crucial role in CNS diseases. Microglia adopt distinct profiles to perform differential functions in various diseases. In this review, we summarize the molecular programs that govern microglial development from embryonic colonization to postnatal maturation, and highlight how these regulatory mechanisms shape microglial identity and function. We further discuss how microglia undergo profound profile transitions in cerebral disorders, especially during ischemic stroke. Together, these insights gained from recent studies highlight the need for a better understanding of the precise cell types and their stage-specific mechanism in the revolution of the immune landscape at different stages of stroke pathology. This knowledge will be valuable to design specific therapeutic strategies to reduce acute and secondary neuronal damage without further exacerbating stroke-induced immune suppression (SIIS).