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These cascades occur over multiple time-scales, with the initial rapid changes in cell metabolism and ionic concentrations trigging several damaging agents that may ultimately leads to cell death.

Tissue affected by ischemic stroke is divided into three regions; 1. Multiscale modeling and multiphysics modeling is essential to capture this cascade.

Such modeling requires coupling complex intracellular molecular alterations with electrophysiology, and consideration of network properties in the context of bulk tissue alterations mediated by extracellular diffusion. Spreading depression is a wave of depolarization that propagates through tissue and causes cells in the penumbra to expend energy by repolarization, increasing their vulnerability to cell death.