Excitotoxins in neuronal apoptosis and necrosis

Neuronal loss is common to many neurodegenerative diseases. Although necros is is a common histopathologic feature observed in neuropathologic conditio ns, evidence is increasing that apoptosis can significantly contribute to n euronal demise. The prevalence of either type of cell death, apoptosis or n ecrosis, and the relevance for the progression of disease is still unclear. The debate on the occurrence and prevalence of one or the other type of de ath in pathologic conditions such as stroke or neurotoxic injury may in par t be resolved by the proposal that different types of cell death within a t issue reflect either partial or complete execution of a common death progra m. Apoptosis is an active process of cell destruction, characterized morpho logically by cell shrinkage, chromatin aggregation with extensive genomic f ragmentation, and nuclear pyknosis. In contrast, necrosis is characterized by cell swelling, linked to rapid energy loss, and generalized disruption o f ionic and internal homeostasis. This swiftly leads to membrane lysis, rel ease of intracellular constituents that evoke a local inflammatory reaction , edema, and injury to the surrounding tissue. During the past few years, o ur laboratories have studied the signals and mechanisms responsible for ind uction or prevention of apoptosis/necrosis in neuronal injury and this is t he subject of this review.