Programmed cell death dynamics during hyperglycemia and ischemic brain injuries.

Abstract

Ischemia-reperfusion injuries of the brain are serious conditions that involve a high degree of programmed cell death. The two major pathways of programmed cell death which are widespread among mammalian cells, apoptosis and necroptosis, drive the damage of these injuries. In this mini-review, the signaling that underlies both of these programmed cell death pathways is broken down, highlighting important overlap and differences between the two pathways. The roles of both apoptosis and necroptosis in driving the pathology of ischemic brain injuries are also outlined. Special attention is paid to the balance between apoptosis and necroptosis in ischemic brain injuries and recent findings that demonstrate that hyperglycemia upregulates necroptosis and may shift apoptosis to necroptosis. The significance of these recent findings are discussed with regard to their role in ischemia-reperfusion injury of the brain and possible underlying mechanisms and avenues for further research on the topic are considered.