Functional Reelin signaling deficits without interneuron loss are associated with neuroblast misplacement after non-convulsive status epilepticus.

Non-convulsive status epilepticus (NCSE) accounts for 20 to 40% of all observed cases of status epilepticus in the intensive care unit, but its early cellular and molecular consequences remain poorly understood. Here, we investigated early dentate gyrus alterations after pilocarpine-induced NCSE, focusing on whether neuroblast misplacement is associated with loss of Reelin-positive hilar interneurons or with functional impairment of Reelin signaling. Using cellular, molecular and imaging analyses, we found that NCSE was associated with reduced positioning of DCX-positive neuroblasts in the granule cell layer and diminished contacts between DCX-positive neuroblasts and GFAP-positive radial glia-like cells. These alterations occurred in the absence of a significant reduction in the number of Reelin-positive hilar interneurons, but were accompanied by reduced extracellular Reelin intensity, altered Reelin processing, and accumulation of intracellular Reelin clusters. Thus, in contrast to more severe convulsive status epilepticus models in which interneuron loss is prominent, our data support an early NCSE phenotype dominated by functional impairment of Reelin signaling. Two-day bumetanide treatment improved selected post-NCSE alterations, including extracellular Reelin processing, RGL-neuroblast contacts, intracellular Reelin clustering and EGR1 expression in Reelin-positive interneurons, and is therefore used here as a pharmacological probe of chloride-transport-associated mechanisms rather than as definitive evidence for direct central NKCC1 inhibition or therapeutic efficacy. These findings highlight NCSE as a distinct pathological entity and suggest that chloride-transport-sensitive changes in interneuron functional state may influence Reelin signaling and neuroblast positioning after seizures.