Delayed Neuronal Death in Ischemic Stroke: Molecular Pathways

Ischemic stroke is caused by a loss of blood flow and deficiency in glucose and oxygen to the brain. The lack of sufficient glucose and oxygen results in varying degrees of tissue damage and cell death following stroke. Reperfusion of blood flow after ischemia often compounds tissue damage that is sustained during the initial drop in local blood availability. The size and position of the affected region depends on which vessel is occluded. A complete loss of blood flow is rare, as rich networks of nearby blood vessels often compensate for reduced flow. The centre of the ischemic region, the core, is characterized by acute and mostly necrotic cell death resulting from severe anoxia and hypoglycemia. The region enveloping the core is known as the penumbra, which experiences a milder ischemic insult. The penumbra should be targeted for treatment strategies; it is usually much larger than the core and has a longer window of opportunity during which neurons can be prevented from dying. Many studies elucidate the molecular pathways of delayed neuronal death. This chapter presents the pathways and strategies that have been investigated to date.