Abstract
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 7–10days of the postictal period. At 1day 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.
Highlights
Seizures provide a profoundly aberrant input to the brain, perturbing normal patterns of neuronal activity and initiating structural and functional changes that persist well beyond the ictal event [1,2,3,4,5,6]
We demonstrate that the core postictal behavioral deficit after status epilepticus (SE) is anxiety-like behavior and that the persistence of SE-induced behavioral changes varies with developmental stage
Performance: Status epilepticus at P15 had no effect on Barnes Maze performance
Summary
Seizures provide a profoundly aberrant input to the brain, perturbing normal patterns of neuronal activity and initiating structural and functional changes that persist well beyond the ictal event [1,2,3,4,5,6]. Individuals with epilepsy frequently report a “postictal state,” temporary affective and cognitive changes that last for hours to days after seizures, including deficits in attention, concentration and short term memory; anxiety, depression, lethargy, and confusion, and in rare cases, postictal psychosis [7, 8, 10]. Most investigations of functional deficits in developing animals, for example, have postponed assessment until adulthood, typically testing at least 1-2 months after seizures [12,13,14,15] Those that have investigated postictal symptoms have mainly focused on the period immediately after seizures [16, 17], failing to reflect that clinically, the emergence of neuropsychiatric symptoms may be delayed for several hours [10]. Regional quantification of KA-SE induced cell injury has been limited to acute time points (24-48 h) and has rarely included the subacute postictal period [18]
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