Multiscale simulation of spreading depolarization in ischemic stroke

Occlusion of a blood vessel in the brain triggers a cascade of changes, including: 1. synaptic glutamate release, related to excitotoxicity; 2. elevated extracellular potassium, leading to spreading depolarization (depression); 3. edema due to cell swelling, reducing the extracellular volume and increasing the tortuosity; 4. production of reactive oxygen species, which gives rise to inflammation and direct cellular damage. These cascades occur over multiple time-scales, with the initial rapid changes in cell metabolism and ionic concentrations triggering several damaging agents that may ultimately lead to cell death. At the tissue scale coincident diffusion may divide ischemic tissue into distinct patterns of pathology, with the ischemic core surrounded by several types of ischemic penumbrae, with cells that are damaged but salvageable.