Apoptotic cell death progression after photothrombotic focal cerebral ischaemia: effects of the lipophilic iron chelator 2,2′-dipyridyl

Autor: Alain Beley, Michaël Van Hoecke, Christine Marie, Laurent Prévotat, Anne Prigent-Tessier, Nathalie Bertrand
Rok vydání: 2005
Předmět:
Zdroj: European Journal of Neuroscience. 22:1045-1056
ISSN: 1460-9568
0953-816X
DOI: 10.1111/j.1460-9568.2005.04297.x
Popis: Two different forms of cell death have been distinguished morphologically following cerebral ischaemia: necrotic and apoptotic cell death. The aim of this study was to investigate the contribution of apoptosis to ischaemic damage by carefully depicting the temporal and spatial neuronal death following focal ischaemia. For this purpose, rats were subjected to chemical photothrombosis, and histological and biochemical analyses were performed over a period of 24 h after the onset of ischaemia. In addition, the effects of the lipophilic antioxidant iron chelator 2,2'-dipyridyl (DP) were evaluated 24 h after photothrombosis when the lesion volume was maximal. Our results showed two separate waves of neuronal death. In the first wave, shrunken dark neurons were massively present as early as 2 h after photothrombosis in the infarct core. From this initial neuronal abnormal population, progressive and time-dependent changes of both necrotic and apoptotic cell death were observed, leading to ghost neurons and apoptotic bodies after 24 h. The extension of the lesion coincided with a second wave of cell death. Massive and rapid neuronal loss occurred at the infarct border, which appeared as a sharply demarcated pale region. Procaspase and poly(ADP-ribose) polymerase-1 (PARP-1) cleavages were also detected in the infarct core and surrounding damaged tissue. DP treatment markedly blocked the enlargement of the lesion, the infarct border being rescued from infarction. Furthermore, a large decrease of apoptotic bodies was associated with a significant drop of caspase and PARP-1 cleavages, suggesting that the protective effect of DP closely correlates with limitation of apoptosis expansion.
Databáze: OpenAIRE
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