Apoptosis may contribute to a significant proportion of neuron death following acute brain
ischemia (ABI), but the underlying mechanisms are still not fully understood. Brain ischemia may lead to
stroke, which is one of the main causes of long-term morbidity and mortality in both developed and developing
countries. Therefore, stroke prevention and treatment is clinically important.
There are two important separate areas of the brain during ABI: the ischemic core and the ischemic penumbra.
The ischemic core of the brain experiences a sudden reduction of blood flow, just minutes after
ischemic attack with irreversible injury and subsequent cell death. On the other hand, apoptosis within the
ischemic penumbra may occur after several hours or days, while necrosis starts in the first hours after the
onset of ABI in the ischemic core. ABI is characterized by key molecular events that initiate apoptosis in
many cells, such as overproduction of free radicals, Ca2+ overload and excitotoxicity. These changes in
cellular homeostasis may trigger either necrosis or apoptosis, which often depends on cell type, cell age,
and location in the brain. Apoptosis results in DNA fragmentation, degradation of cytoskeletal and nuclear
proteins, cross-linking of proteins, formation of apoptotic bodies, expression of ligands for phagocytic
cell receptors and finally uptake by phagocytic cells.
This review focuses on recent findings based on animal and human studies regarding the apoptotic
mechanisms of neuronal death following ABI and the development of potential neuroprotective agents
that reduce morbidity. The effects of statins on stroke prevention and treatment as well as on apoptotic
mediators are also considered.