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

Cell loss in the hippocampal formation is a common event in patients with t emporal lobe epilepsy. The belief that dentate granule neurons are relative ly resistant to excitotoxic injury has recently been challenged both, in ep ileptic patients and in animal models of temporal lobe epilepsy. The nature of dentate granule cell damage in epilepsy has been reported as either apo ptotic, necrotic or both. The lack of a consensus on this topic stems from use of different animal models and different experimental techniques for ch aracterizing the apoptotic/necrotic process. Using electron microscopy for defining the, nature of cell loss and one of the main animal models of stat us epilepticus (SE) we have focussed on the nature of the degenerative proc ess in dentate granule cells. Ultrastructural morphological changes of thes e cells were evaluated 2.5-48 h after pilocarpine-induced status epilepticu s. A variety of morphologies ranging from apoptosis to necrosis, could be s een 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. I n such cases however, chromatin did not have well-defined edges las it shou ld, if it were apoptosis). Condensation of cytoplasm. present in both proce sses was also frequently found. Neither obvious apoptotic budding-off of cy toplasm nor typical membrane-bound apoptotic bodies were found. Our results indicate that in the dentate granule cell layer pilocarpine-induced SE pro motes a degenerative process in which apoptotic and necrotic features overl ap. (C) 2000 Elsevier Science B.V. All rights reserved.