Microglia in epilepsy

Epilepsy is one of most common chronic neurological disorders, and the antiseizure medications developed by targeting neurocentric mechanisms have not effectively reduced the proportion of patients with drug-resistant epilepsy. Further exploration of the cellular or molecular mechanism of epilepsy is expected to provide new options for treatment. Recently, more and more researches focus on brain network components other than neurons, among which microglia have attracted much attention for their diverse biological functions. As the resident immune cells of the central nervous system, microglia have highly plastic transcription, morphology and functional characteristics, which can change dynamically in a context-dependent manner during the progression of epilepsy. In the pathogenesis of epilepsy, highly reactive microglia interact with other components in the epileptogenic network by performing crucial functions such as secretion of soluble factors and phagocytosis, thus continuously reshaping the landscape of the epileptic brain microenvironment. Indeed, microglia appear to be both pro-epileptic and anti-epileptic under the different spatiotemporal contexts of disease, rendering interventions targeting microglia biologically complex and challenging. This comprehensive review critically summarizes the pathophysiological role of microglia in epileptic brain homeostasis alterations and explores potential therapeutic or modulatory targets for epilepsy targeting microglia.