Cell damage and neurogenesis in the dentate granule cell layer of adult rats after pilocarpine- or kainate-induced status epilepticus

Dentate granule cells are generally considered to be relatively resistant t o excitotoxicity and have been associated with robust synaptogenesis after neuronal damage. Synaptic reorganization of dentate granule cell axons, the mossy fibers, has been suggested to be relevant for hyperexcitability in h uman temporal lobe epilepsy and animal models. A recent hypothesis suggeste d that messy-fiber sprouting is dependent on newly formed dentate granule c ells. However, we recently demonstrated that cycloheximide (CHX) can block the messy-fiber sprouting that would otherwise be induced by different epil eptogenic agents and does not interfere with epileptogenesis in those model s. Here, we investigated cell damage and neurogenesis in the dentate gyrus of pilocarpine- or kainate-treated animals with or without coadministration of CHX. Dentate granule cells were highly vulnerable to pilocarpine induce d-status epilepticus (SE), but were hardly damaged by kainate-induced SE. C HX pretreatment markedly reduced the number of injured neurons after piloca rpine-induced SE. Induction of SE dramatically increased the mitotic rate o f KA-and KA + CHX-treated animals. Induction of SE in animals injected with pilocarpine alone led to 2-7-fold increases in the mitotic rate of dentate granule cells as compared to 5- and 30-fold increases for pilocarpine + CH X animals. We suggest that such increased mitotic rates might be associated with a protection of a vulnerable precursor cell population that would oth erwise degenerate after pilocarpine-induced SE. We further suggest that mes sy-fiber sprouting and neurogenesis of granule cells are not necessarily li nked to one another. (C) 2000 Wiley-Liss, Inc.