Ischemic preconditioning (IPC) represents an important adaptation of CNS to sub-lethal
ischemia, which results in increased tolerance of CNS to the lethal
ischemia.
Ischemia-induced mitochondrial apoptosis is considered to be an important event leading to neuronal cell death after cerebral blood flow arrest. In presented study, we have determined the effect of IPC on
ischemia/reperfusion-induced mitochondrial apoptosis. Global
brain ischemia was induced by permanent occlusion of vertebral arteries and temporal occlusion of carotid arteries for 15 min. Rats were preconditioned by 5 min of sub-lethal
ischemia and 2 days later 15 min of lethal
ischemia was induced. With respect to mitochondrial apoptosis initiation, translocation of p53 to mitochondria was observed in hippocampus but not in cerebral cortex. However, level of both apoptotic bax and anti-apoptotic bcl-xl in both hippocampal and cortical mitochondria was unchanged after global
brain ischemia. Detection of genomic DNA fragmentation as well as
Fluoro-Jade C staining showed that
ischemia induces apoptosis in vulnerable CA1 layer of rat hippocampus. IPC abolished completely
ischemia-induced translocation of p53 to mitochondria and had significant protective effect on
ischemia-induced DNA fragmentation. In addition, significant decrease of
Fluoro-Jade C positive cells was observed as well. Our results indicate that IPC abolished almost completely both initiation and execution of mitochondrial apoptosis induced by global
brain ischemia.