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Apoptosis and Acute Brain Ischemia in Ischemic Stroke

[ Vol. 15 , Issue. 2 ]

Author(s):

Djordje Radak, Niki Katsiki, Ivana Resanovic, Aleksandra Jovanovic, Emina Sudar-Milovanovic, Sonja Zafirovic, Shaker A. Mousad and Esma R. Isenovic   Pages 115 - 122 ( 8 )

Abstract:


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.

Keywords:

Apoptosis, acute brain ischemia, stroke, caspase, death receptor, statins.

Affiliation:

Laboratory of Radiobiology and Molecular Genetics, Institute Vinca, University of Belgrade, P.O.Box 522, 11000 Belgrade

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