Extrinsic and intrinsic pathways of apoptosis and related molecules in ischemic stroke

Cerebral ischemia is a disease in which there is no enough blood flow to provide essential nutrients for brain activity and metabolism. Following the stroke, the occurrence of two types of disorders is probable, including ischemia (85%) and haemorrhage (15%). In cerebral ischemia conditions, various mechanisms cause neural death, including increased extracellular glutamate amino acid concentration, inflammation, oxidative stress, apoptosis, and necrosis-induced cell death. Each of these mechanisms can potentially spread into the adjacent cells and tissues through distinct molecular cascades. Although several mechanisms are involved in cerebral ischemia pathogenesis, apoptosis plays a major role in cell death following cerebral ischemia. After the onset of focal cerebral ischemia, the core region in the ischemic brain with severe blood flow is lethally damaged, leading to cell death. Following cerebral ischemia, apoptosis occurs through two general pathways of intrinsic and extrinsic. The role of mitochondria and the released cytochrome C leading to stimulation of caspase-3 is prominent in the intrinsic pathway. But, the extrinsic pathway initiates with the activity of death receptors located on the cell surfaces of neurons, causing stimulation of caspase-8. Calpain, caspases, and c-Jun N-terminal kinases are considered key molecules involved in the cell apoptosis molecular pathway. This study aimed to describe the apoptosis process in cerebral ischemia by the use of key apoptotic molecules.