Microglial phagocytosis in epilepsy: Mechanisms and impact

Microglia are resident immune cells critical in maintaining brain homeostasis via their surveillance and phagocytosis function. Under disease contexts such as seizures and epilepsy, microglial phagocytic signalling is activated in response to both inflammatory and non-inflammatory cell death. This process involves a range of well-characterized 'find me' and 'eat me' signals, phagocytic receptors, and less well-characterized intracellular signalling pathways. In addition, epigenetic and transcriptional regulators orchestrate microglial responses to seizures, including the integration of phagocytic and inflammatory pathways. Interestingly, although inhibiting phagocytosis has been shown to improve neuronal survival and cognitive performance after seizures, it paradoxically increases the risk of developing spontaneous recurrent seizures. Reconciling these dual effects requires a deeper understanding the spatiotemporal dynamics of microglial phagocytosis. The objective of this review is to examine the mechanisms and impact of microglial phagocytosis in the context of epilepsy and to highlight unresolved questions that warrant further investigation in this emerging field.