Microglial pathological synaptic pruning in epilepsy: pathophysiology and therapeutic potential

Epilepsy affects around 70 million people worldwide, and roughly one-third of them respond poorly to standard antiepileptic drugs. Current treatments are directed almost entirely at neurons, leaving the contribution of non-neuronal cells largely unaddressed. Microglia, the resident immune cells of the central nervous system, both support neuronal survival and shape neural circuits by pruning synapses through "eat-me" and "don't-eat-me" signals. In epilepsy, this pruning becomes dysregulated: microglia preferentially eliminate inhibitory synapses, producing excitatory/inhibitory (E/I) imbalance, synchronized network discharges, and a lowered seizure threshold. This review summarizes recent work on pathological synaptic pruning by microglia in epilepsy, focusing on the signaling pathways that drive the process and on whether they can be targeted therapeutically in drug-resistant epilepsy. The broader goal is to suggest new treatment directions beyond conventional, neuron-targeted pharmacology.