title: Kainic acid induces rapid cell death followed by transiently reduced cell proliferation in the immature granule cell layer of rat organotypic hippocampal slice cultures.
abstract: Brain injury due to seizures results in transiently increased cell proliferation and neurogenesis in the subgranular zone of the adult dentate gyrus. In contrast, the immature postnatal brain appears to be more resistant to cell death after seizure-induced brain injury and paradoxically reacts to seizures by reducing SGZ proliferation. Organotypic hippocampal slice cultures are a useful paradigm for modelling the early postnatal hippocampus. We have investigated the temporal relationship between cell death and cell proliferation after kainate in the granule cell layer of rat organotypic hippocampal slice cultures equivalent to post natal day 11 animals. We found stable numbers and densities of mature thionine stained cells in the granule cell layer over 72 h in control cultures grown in defined medium. We also found a slowly declining cell proliferation rate over the same time period under control conditions. We report evidence of early cell death in the granule cell layer after just 2 h exposure to 5 microM kainate, followed by a significant decrease in cell proliferation in the granule cell layer at 24 h. In contrast to control conditions, cell proliferation rose significantly in the kainate exposed cultures by 72 h back to levels seen at 2 h. There were no significant changes in cell labelling with antibody to activated caspase-3 between kainate treated and control cultures at any time point examined. Our results suggest that kainate-induced injury in the early postnatal hippocampus damages precursor cells contributing to a reduction in granule layer cell proliferation.
authors.affiliation: Division of Clinical Neurosciences, Southampton Neurosciences Group, School of Medicine, University of Southampton, Room 6207, Level 6, Biomedical Sciences Building, Bassett Crescent East, Southampton SO16 7PX, UK.
authors.forename: Matthew Paul
authors.initials: MP
authors.lastname: Sadgrove
authors.forename: John E
authors.initials: JE
authors.lastname: Chad
authors.forename: William Peter
authors.initials: WP
authors.lastname: Gray
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D007608:Kainic Acid / Q000494:pharmacology*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D006131:Growth Inhibitors; D007608:Kainic Acid