Acute Status Epilepticus Triggers Long‐Term Neurogenic Niche Destabilization That Undermines Cognitive Function in the Excitotoxic FVB/N Hippocampus

The adult hippocampus is highly susceptible to excitotoxic injury, although the extent to which acute seizure episodes dictate long‐term cognitive outcomes through neurogenic niche remodeling remains incompletely understood. This study investigated the hypothesis that an isolated episode of sustained status epilepticus (SE) is sufficient to trigger persistent alteration of the adult neurogenic niche, followed by neurostructural and functional discrepancies. Acute SE was induced in young FVB/N mice via a single systemic dose of kainic acid. Dentate morphological remodeling was quantitatively characterized using immunostaining, Golgi‐Cox staining, SNT‐Sholl analysis, and confocal microscopy. Behavioral paradigms assessed anxiety, despair, and spatial/recognition memory, while correlation coefficient was used to establish structure–function correlations. Acute SE triggered the rapid activation of reactive adult neural stem cells (HopX + GFAP + ), followed by a critical polarity shift and a fate transition from neurogenic (GFAP + S100β − ) to non‐neurogenic (GFAP + S100β + ) lineages, thereby driving widespread reactive gliosis. This niche destabilization was accompanied by collapse of dentate neuronal architecture, characterized by ectopic DCX + cell localization, asymmetrical neuronal clustering, primary dendritic ramification defects, abnormal and complex branching patterns, and disrupted dendritic spine microanatomy. These structural aberrations displayed a robust, graded correlation with increased anxiety, behavioral despair, and profound deficits in recognition and spatial memory. Our results demonstrate that even a discrete, acute seizure episode precipitates enduring disruption of the hippocampal adult neurogenic niche and long‐lasting structural and behavioral abnormalities. This study highlights that early destabilization of the neurogenic niche is an underrecognized pathophysiological process associated with irreversible hippocampal remodeling and cognitive deficits following SE.