Microglial phagocytosis/apoptosis coupling in health and disease.

<p>In physiological conditions as well as during excitotoxicity and inflammation, microglial phagocytosis is tightly coupled to apoptosis due to “find-me” signals released by apoptotic cells, such as ATP. Microglia display a combination of three adaptation strategies to boost their phagocytic efficiency: recruit more phagocytic cells, increase the phagocytic capacity per cell, and/or increase the number of cells. In contrast, neuronal hyperactivity induced by seizures leads to a widespread release of ATP, among other possible signals, and interferes with the ability of microglia to recognize and engulf apoptotic cells, resulting in their delayed clearance. Because phagocytosis is actively anti-inflammatory, the phagocytosis impairment was associated with the production of proinflammatory, epileptogenic cytokines.