Ultrastructural identification of dentate granule cell death from pilocarpine-induced seizures

Abstract

Cell loss in the hippocampal formation is a common event in patients with temporal lobe epilepsy. The belief that dentate granule neurons are relatively resistant to excitotoxic injury has recently been challenged both, in epileptic patients and in animal models of temporal lobe epilepsy. The nature of dentate granule cell damage in epilepsy has been reported as either apoptotic, necrotic or both. The lack of a consensus on this topic stems from use of different animal models and different experimental techniques for characterizing the apoptotic/necrotic process. Using electron rnicroscopy for defining the, nature of cell loss and one of the main animal models of status epilepticus (SE) we have focussed on the nature of the degenerative process in dentate granule cells. Ultrastructural morphological changes of these cells were evaluated 2.5–48 h after pilocarpine-induced status epilepticus. A variety of morphologies ranging from apoptosis to necrosis, could be seen at 2.5 h after SE onset and continued at least over the following 48 h. Some cells displayed coalescence of chromatin against nuclear membranes. In such cases however, chromatin did not have well-defined edges (as it should, if it were apoptosis). Condensation of cytoplasm. present in both processes was also frequently found. Neither obvious apoptotic budding-off of cytoplasm nor typical membrane-bound apoptotic bodies were found. Our results indicate that in the dentate granule cell layer pilocarpine-induced SE promotes a degenerative process in which apoptotic and necrotic features overlap.