RT Journal Article SR Electronic T1 Specific Caspase Pathways Are Activated in the Two Stages of Cerebral Infarction JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 7127 OP 7134 DO 10.1523/JNEUROSCI.21-18-07127.2001 VO 21 IS 18 A1 Alexandra Benchoua A1 Christelle Guégan A1 Cécile Couriaud A1 Hassan Hosseini A1 Nathalie Sampaı̈o A1 Didier Morin A1 Brigitte Onténiente YR 2001 UL http://www.jneurosci.org/content/21/18/7127.abstract AB Necrosis and apoptosis have been initially identified as two exclusive pathways for cell death. In acute brain lesions, such as focal ischemia, this binary scheme is challenged by demonstrations of mixed morphological and biochemical characteristics of both apoptosis and necrosis in single cells. The resulting difficulty in defining the nature of cell death that is triggered by severe insults has dramatically impeded the development of therapeutic strategies. We show that in the early stages of cerebral infarction, neurons of the so-called “necrotic” core display a number of morphological, physiological, and biochemical features of early apoptosis, which include cytoplasmic and nuclear condensations and specific caspase activation cascades. Early activation cascades involve the death receptor pathway linked to caspase-8 and the caspase-1 pathway. They are not associated with alterations of mitochondrial respiration or activation of caspase-9. In contrast, pathways that are activated during the secondary expansion of the lesion in the penumbral area include caspase-9. In agreement with its downstream position in both mitochondria-dependent and -independent pathways, activation of caspase-3 displays a biphasic time course. We suggest that apoptosis is the first commitment to death after acute cerebral ischemia and that the final morphological features observed results from abortion of the process because of severe energy depletion in the core. In contrast, energy-dependent caspase activation cascades are observed in the penumbra in which apoptosis can fully develop because of residual blood supply.