Abstracts

In rat pups neurogenesis of the dentate gyrus is constrained by seizures where in adult rats it is provoked. To determine long-term effects of a single episode of status epilepticus on the developing hippocampus we examined neurogenesis after kainate (KA) administration in pups on postnatal (P) day 13 and then let them grow to adults. To determine whether neurogenesis is affected just by the seizure itself and or by cell death, neurogenesis was also examined in adult rats after KA-induced status epilepticus with and without a delay of bromo-deoxyuridine (BrdU) injection. KA was administered on P13 (2 mg/kg, i.p.) and animals were sacrificed on P62. BrdU was injected at the time of KA injection. P60 rats were injected with KA (12 mg/kg) and sacrificed at 48 and 96 hrs. BrdU was injected at the time of KA injection and after a 48 delay when neurodegeneration is near maximal. Brains were processed for BrdU immunohistochemistry and sections were co-labeled with GFAP. In control P60 rats, BrdU positive nuclei lined the hilar border of the dentate gyrus (DG) and they were few in number (approx. 18). Within molecular layers of the DG additional BrdU-positive cells were observed. A few cells were also detected throughout the rest of the hippocampal layers (approx. 15). In contrast, adult rats injected with KA and BrdU on P13, had BrdU-labeled nuclei deep within the granule cell layers but they were also few in number. The pattern of BrdU-labeled nuclei observed throughout the hippocampus was different from control P60 adults. In adults without delay of BrdU injection and 48 hrs after KA, there was a small increase in the number of BrdU-labeled nuclei within the hilus as reported after pilocarpine seizures, but marked increases were observed in the CA3, particularly the CA3a, highly sensitive to neurodegeneration. In contrast to our expectation, co-labeling with GFAP was minimal. Numbers of BrdU labeled nuclei were elevated further with delayed BrdU injection; the CA1 and ventricular zone were robustly labeled as well as CA3/hilus. Although the number of BrdU-labeled cells did not appear to increase when adults had an early seizure, the altered pattern suggests that one early life seizure could lead to permanently altered hippocampal circuitry in adulthood. The marked increases observed in the CA3/hilus without BrdU delay were not due to proliferating astrocytes. Enhanced elevation of BrdU-labeled cells with BrdU delay suggests that neurodegenerative process also contribute to neurogenesis following status epilepticus. (Supported by NJ Neuroscience Institute)