Apoptosis as a mediator of delayed tissue damage in progressive stroke: a computational study

Abstract

This paper presents a computational model of ischemic stroke that focuses on the role of apoptosis as a mediator of delayed tissue. There is strong evidence that apoptosis (programmed cell death) occurs subsequent to ischemia, but its role as a mediator of delayed cell death has not been examined quantitatively. In this computational study, evidence is presented suggesting that apoptosis can cause tissue damage in a delayed fashion, with a temporal profile similar to that reported in cases of progressive stroke. The results from this study indicate that tissue damage is bi-phasic. In the acute phase (1-3 hours post-ictus), damage in the ischemic focus occurs as a result of severe metabolic insufficiency (necrosis). After a substantial time delay, a second form of cell death becomes apparent - mediated by apoptosis. The combination of necrosis and apoptosis accounts for the final infarct volume occurring in this model of ischemic stroke