Abstracts

Rationale: In adult rats, seizures increase hippocampal neurogenesis. Therefore, short- and long-term effects of multiple episodes of status epilepticus on hippocampal neurogenesis during early development were examined. Methods: Status epilepticus was induced thrice with kainate at ages (P6, P9, P13 or P20). Brains were processed for bromo-deoxyuridine (BrdU) and TUNEL immunohistochemistry, silver impregnation, and electron microscopy at several time points. Results: In control pups, BrdU positive neurons were abundant within the dentate gyrus. Control labeling occurred after two episodes of status epilepticus. Three episodes at P6, P9, and P13, suppressed the number of BrdU positive cells expressed at 48 hrs (489.7 b 77 vs. 224.8 b 36). Numbers were lower if pups were older at the 3rd injection (P6, P9, P20) (395 b 33 vs. 99 b 11.7). In granule cell layers or hilus, neurodegenerative stains showed minimal argyrophilia and TUNEL positive cells were absent. At 48 hrs, electron microscopy revealed many small-irregularly shaped neurons with condensed cytoplasm and electron dense nuclei, presumably stem cells. They were located at the border of the granule cell layer and lacked glial support cells. These were unlike normal immature granule cells found at this site with oval nuclei and a watery cytoplasm. At 72 hrs, some granule cells were electron dense and Nissl stain showed shrunken hyperbasophilic cells throughout the layer. Conclusions: Three episodes of status epilepticus occurring during the first weeks of postnatal development dramatically reduce the number of hippocampal BrdU positive cells and alter granule cell morphology for a prolonged period without inducing cell death. Alterations in small cell ultra-structure and lack of glial support suggest that after three seizure episodes progenitors may not differentiate or migrate properly and could be retarded in an immature state. Supported by NIH-38069 (LKF) and NH-38331 (CER)