SPREADING DEPRESSION IN FOCAL ISCHEMIA - A COMPUTATIONAL STUDY

When a cerebral infarction occurs, surrounding the core of dying tissu e there usually is an ischemic penumbra of nonfunctional but still via ble tissue. One current but controversial hypothesis is that this penu mbra tissue often eventually dies because of the metabolic stress impo sed by multiple cortical spreading depression (CSD) waves, that is, by ischemic depolarizations. We describe here a computational model of C SD developed to study the implications of this hypothesis. After simul ated infarction, the model displays the linear relation between final infarct size and the number of CSD waves traversing the penumbra that has been reported experimentally, although damage with each individual wave progresses nonlinearly with time. It successfully reproduces the experimental dependency of final infarct size on midpenumbra cerebral blood flow and potassium reuptake rates, and predicts a critical penu mbra blood flow rate beyond which damage does not occur. The model rep roduces the dependency of CSD wave propagation on N-methyl-D-aspartate activation. It also makes testable predictions about the number, velo city, and duration of ischemic CSD waves and predicts a positive corre lation between the duration of elevated potassium in the infarct core and the number of CSD waves. These findings support the hypothesis tha t CSD waves play an important causal role in the death of ischemic pen umbra tissue.