Maturation-dependent behavioral deficits and cell injury in developing animals during the subacute postictal period

- Status epilepticus causes acute anxiety-like behavior in developing rats.
- Seizure-induced behavioral deficits are age-dependent and can last for days.
- Status epilepticus causes age-dependent cell injury in the limbic system.
- Persistence of behavioral deficits is temporally correlated with limbic cell injury.

Prolonged early-life seizures are associated with disruptions of affective and cognitive function. Postictal disturbances, temporary functional deficits that persist for hours to days after seizures, have not yet been thoroughly characterized. Here, we used kainic acid (KA) to induce status epilepticus (SE) in immature rats at three developmental stages (postnatal day (P) 15, 21, or 30) and subsequently assessed spatial learning and memory in a Barnes maze, exploratory behavior in an open field, and the spatiotemporal distribution of cell injury during the first 7-10 days of the postictal period. At 1 day post-SE, P15-SE rats showed no deficit in the Barnes maze but were hyperexploratory in an open field compared with their littermate controls. In contrast, P21- and P30-SE rats exhibited markedly impaired performance in the Barnes maze and exhibited significantly reduced open field exploration suggestive of anxiety-like behavior. These behavioral changes were transient in P15 rats but more persistent in P21 and enduring in P30 rats after KA-SE. The time course of behavioral deficits in P21 and P30 rats was temporally correlated with the presence of neuronal injury in the lateral septal nuclei, amygdala, and ventral subiculum/CA1, regions involved in modulation of the hypothalamic-pituitary-adrenal stress response.