Although neonatal seizures are quite common, there is controversy regarding their consequences. Despite considerable evidence that seizures may cause less cell loss in young animals compared with mature animals, there are nonetheless clear indications that seizures may have other potentially deleterious effects. Because it is known that seizures in the mature brain can increase neurogenesis in the hippocampus, we studied the extent of neurogenesis in the granule cell layer of the dentate gyrus over multiple time points after a series of 25 flurothylinduced seizures administered between postnatal day 0 (P0) and P4. Rats with neonatal seizures had a significant reduction in the number of the thymidine analog 5-bromo-2Ј-deoxyuridine-5Ј-monophosphate-(BrdU) labeled cells in the dentate gyrus and hilus compared with the control groups when the animals were killed either 36 hr or 2 weeks after the BrdU injections. The reduction in BrdU-labeled cells continued for 6 d after the last seizure. BrdU-labeled cells primarily colocalized with the neuronal marker neuron-specific nuclear protein and rarely colocalized with the glial cell marker glial fibrillary acidic protein, providing evidence that a very large percentage of the newly formed cells were neurons. Immature rats subjected to a single seizure did not differ from controls in number of BrdUlabeled cells. In comparison, adult rats undergoing a series of 25 flurothyl-induced seizures had a significant increase in neurogenesis compared with controls. This study indicates that, after recurrent seizures in the neonatal rat, there is a reduction in newly born granule cells.

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Summary:Purpose: Status epilepticus (SE) is more common in children than adults and has a high mortality and morbidity rate. SE in adult rats results in long-term disturbances in learning and memory, as well as an enhanced seizure susceptibility to further seizures. In contrast, a number of studies suggest that the immature brain is less vulnerable to the morphologic and physiologic alterations after SE. The goal of this study was to determine whether the long-term consequences of SE during development on hippocampal plasticity and cognitive function are age and model specific.Methods: We used lithium-pilocarpine (Li-PC) to induce SE at different age points during development (P12, P16, P20) and evaluated the effects of this abnormal neural activity on spatial memory performance and seizure susceptibility in the animals beginning at P55, corresponding to young adulthood.Results: We demonstrated that SE at P12 did not result in any structural or functional changes detectable in adulthood, whereas SE at both P16 and P20 induced cell loss and mossy fiber sprouting within the hippocampus and cognitive impairment when the animals were tested as adults.Conclusions: Whereas the seizure threshold to generalized seizures was not altered, animals with SE at P20 showed an increased susceptibility to kindling in adulthood. Key Words: Epilepsy-Seizures-Immature brain-LearningPilocarpine.Status epilepticus (SE), an acutely life-threatening event characterized by repetitive or prolonged seizures, is a common pediatric emergency. Approximately 10% of children and adults who have a first unprovoked seizure or newly diagnosed epilepsy have SE (1,2). SE is more common in children than in adults, with half of the total cases occurring in those younger than 2 years (3). In the clinical literature, some reports indicate that SE in the immature brain is less harmful than SE in adults (4,5). However, recent studies suggest that SE can result in brain damage, resulting in long-term cognitive impairment and permanent susceptibility to future seizures (6-8).Likewise, in rodent studies, the pathophysiologic effects of SE appear to vary as a function of age (9-12). Severe seizures in pubescent rats can produce persistent neuronal dysfunction, resulting in deficits in learning and memory (13-15) and an enhanced susceptibility to further seizures (16,17). Damage in the developing hippocampus, a structure implicated in both memory acquisition and seizure expression, may be responsible for these effects. Abnormal neural activity such as seizures during its development might have effects on the developing circuitry, particularly in the dentate gyrus (DG), modifying the development of synaptic connections and therefore influencing hippocampal function in adulthood. Although the immature hippocampus is highly susceptible to seizure, and experimental seizures induced in immature rats are typically more severe than those in adults (18), a number of studies suggest that the immature brain is less vulnerable to the morphologic and physiologic alterati...