Abstracts

RATIONALE: Granule cell (GC) proliferation in adult rodents is enhanced by both physiological and pathological stimuli, including prolonged or recurrent limbic seizures. Though the precise consequences of GC proliferation remain unclear, this phenomenon may play a role in epileptogenesis following acute seizure induction. Prolonged febrile seizures (FS) in the immature rat result in transient injury to pyramidal neurons as well as to permanently enhanced susceptibility to excitatory input to hippocampal circuits. This study tested the hypothsis that enhanced GC neurogenesis may contribute to the increased hippocampal excitability observed after prolonged FS. METHODS: Immature rats (postnatal day 10; N=18) subjected to hyperthermic seizures, a model for prolonged FS (Dube et al. Ann Neurol, 2000), were compared with hyperthermic and normothermic controls. To distinguish proliferating cells, rats were injected with BrdU 3 or 7 days later, and perfused after 48h (P15 or P19). Quantitative analysis of BrdU-immunolabeled cells within the GC layer and in the hilus was performed without knowledge of treatment. RESULTS: Numbers of BrdU-labeled cells in FS-sustaining rats did not differ from those of control at either timepoints. However, age-dependent reduction in GC proliferation rate was noted (Means +/- standard deviations in controls vs. FS rats: 1877+/-402 vs 1800+/-283 at P15; 790+/-147 vs 731+/-94 at P19) CONCLUSIONS: In contrast to the effects of adult prolonged seizures on neurogenesis, prolonged FS in immature rat did not alter GC proliferation rate. Whether this fact relates to seizure duration or to inherent differences between mature and developing dentate gyrus is the focus of current investigation. Supported by NS35439.