Ethidium bromide staining reveals rapid cell dispersion in the rat dentategyrus following ouabain-induced injury

The dentate gyrus of the hippocampal formation undergoes extensive network remodelling including progenitor cell proliferation, migration as well as a poptotic cell death in response to prolonged excitotoxic insults. Previous studies have shown that such a proliferative cell population may undergo ab errant migration and later persist in ectopically located positions within the molecular cell layer. In this study we have developed an experimental m odel to characterize the spatiotemporal patterns of such an injury-induced network remodelling. Ouabain (1 mu l, 1 mM), a Na+, K+-ATPase blocker, was stereotactically co-injected into the rat dentate gyrus with ethidium bromi de (1 mu l 40 mu M) The latter is a fluorescent nucleic acid intercalating dye, which was used for labeling cells undergoing early phases of apoptosis or proliferation. Our results revealed that within an hour after the injec tion, a subpopulation of cells characterized by spindle- or ovoid-shaped so mata and bipolar morphology, were intensely labeled with ethidium bromide. These cells were found initially clustered both inside and outside the dent ate granule cell layer and later on markedly increased in number as well as spread radially in the next few hours into the dentate molecular layer. The unusual pattern of cell dispersion encountered in our study may represe nt aberrantly migrating progenitor cells consistent with earlier observatio ns of ectopically-located granule cells in human temporal lobe epilepsy spe cimens and epilepsy animal models. Alternatively, the described phenomenon may represent dispersion of Cajal-Retzius cells that may be involved in pos tlesion network remodelling. (C) 1999 IBRO. Published by Elsevier Science L td.