Status epilepticus (SE) led to reduced miR-124 expression via SIRT1-and, in turn, miR-124 repression-via C/EBPα upregulated NRSF. SE-sustaining animals developed epilepsy, but supplementing miR-124 did not modify epileptogenesis. Synthetic miR-124 not only effectively blocked NRSF upregulation and rescued NRSF target genes, but also augmented microglia activation and inflammatory cytokines. Thus, miR-124 attenuates epileptogenesis via NRSF while promoting epilepsy via inflammation.