Microglial phagocytosis and regulatory mechanisms after stroke

Stroke, including ischemic stroke and hemorrhagic stroke can cause massive neuronal death and disruption of brain structure, which is followed by secondary inflammatory injury initiated by pro-inflammatory molecules and cellular debris. Phagocytic clearance of cellular debris by microglia, the brain's scavenger cells, is pivotal for neuroinflammation resolution and neurorestoration. However, microglia can also exacerbate neuronal loss by phagocytosing stressed-but-viable neurons in the penumbra, thereby expanding the injury area and hindering neurofunctional recovery. Microglia constantly patrol the central nervous system using their processes to scour the cellular environment and start or cease the phagocytosis progress depending on the eat me or don't eat me'' signals on cellular surface. An optimal immune response requires a delicate balance between different phenotypic states to regulate neuro-inflammation and facilitate reconstruction after stroke. Here, we examine the literature and discuss the molecular mechanisms and cellular pathways regulating microglial phagocytosis, their resulting effects in brain injury and neural regeneration, as well as the potential therapeutic targets that might modulate microglial phagocytic activity to improve neurological function after stroke.

Automated summary

Stroke can cause neuronal death and disruption of brain structure, leading to secondary inflammatory injury. Microglia, as scavenger cells in the brain, play an important role in the clearance of cellular debris. However, they can also exacerbate neuronal loss by phagocytosing stressed-but-viable neurons. The optimal immune response requires a delicate balance between different phenotypic states to regulate neuro-inflammation and facilitate reconstruction after stroke.