Abstracts

Rationale: Long-term (LT) effects of a single episode of kainate (KA) induced status epilepticus initiated in the perinatal period on hippocampal neurogenesis remain unknown. Therefore, we determined whether one early-life seizure induced on postnatal day 13 (P13) could have lasting effects into adulthood and whether these resemble short-term (ST) effects of a seizure later in life, P60. Methods: We used single and double immunohistochemistry to study newly dividing cells throughout the hippocampus with antibodies bromo-deoxyuridine (BrdU) and Ki67, which label different stages of the cell cycle; neuronal and non-neuronal cell markers were used to identify cell types affected. Results: In control rats, few scattered BrdU+ and Ki67+ dividing cells were detected lining the hilar border and other hippocampal layers. In contrast, ST rats expressed high numbers of BrdU+ and Ki67+ dividing cells within 48 hrs throughout hippocampal subfields. LT rats revealed a significant increase in the number of BrdU, but not Ki67, labeled nuclei within the CA3 and molecular cell layer (MCL) of the dentate gyrus (DG). Although there was no significant increase in progenitors within the granule cell layer (GCL), many BrdU+ cells were deeply incorporated, resembling the ST rats. Dispersion of the GCL was also noted in LT rats in various regions of dorsal and ventral blades. Percentages of proliferating cells co-labeling with neuronal and non-neuronal cell markers differed according to experimental group. Conclusions: In ST rats, increased proliferation was observed with both antibodies; therefore, enhanced proliferation likely occurred around the time of the seizure, on P60. Accordingly, increases in LT rats were only detected with the BrdU marker, suggesting enhanced proliferation of newly dividing cells also occurred around the time of the seizure, on P13. Elevation of neuronal and non-neuronal progenitors following seizures in certain parts of the DG and altered distribution in the GCL of both groups suggests progenitors are not restricted to areas of neuronal vulnerability and incorporation of newly born granule cells occurs at the time of the insult. These may lead to permanently altered patterns of hippocampal circuitry regardless of when prolonged seizure episodes occur.