Development of seizure susceptibility is coincident with a tight time window that is required for accumulation of neural progenitors in the dorsal hippocampus .

Abstract

Kindled seizures are widely used to model epileptogenesis, but the molecular mechanisms underlying the attainment of kindling status are largely unknown. Accumulating evidence suggests that neurogen-esis could be a major event that contributes to seizure susceptibility rather than a side effect of seizure activity. Recently we showed that optimal achievement of kindling status in the Sprague-Dawley rat is associated with a critical developmental interval of 25 ± 1 days. We hypothesized that neurogenesis-related cellular (survival) differentia-tion events with this periodicity may underlie the tightly circumscribed window for the optimal induction of convulsive seizure. By real-time PCR, quantitative immunohistochemistry and confocal 3D-image reconstruction analysis using tissue from this new model, we now re-port that convulsive seizure leads first to a non-specific, transient in-crease in the number of proliferative cells that express the proliferating cell nuclear antigen-, nestin-, ßIII-tubulin and doublecortin. However, repeated convulsive seizures with a periodicity of 25 days led to a massive and selective increase in the number of new-born cells expressing the neuronal lineage marker, doublecortin, at the boundary between the granule cell layer and the polymorphic layer in the dorsal hippocampus.