Microglia in Epilepsy: From Circuit Modulators to Therapeutic Targets

Abstract

Epilepsy affects over 50 million people worldwide, with one-third resistant to drugs. Once seen as a disorder of neuronal hyperexcitability, it's now recognized as involving complex network dysfunction, where non-neuronal cells, especially microglia, play active roles. Microglia regulate synaptic activity, immune surveillance, and circuit remodeling. They monitor extracellular changes, detect ATP from hyperactive neurons, and respond with process motility. Studies show microglia can both reduce hyperactivity by spine contact and promote excitation by stimulating dendritic filopodia and new synapses. This dual role places microglia at the junction of stability and hyperexcitability. Evidence links maladaptive microglial responses to epileptogenesis, seizures, and network instability, highlighting the importance of glial and immune pathways as therapeutic targets.