An ischemic penumbra has the potential for functional recovery provided that 
local blood flow can be reestablished, but irreversible damage will develop 
without sufficient reperfusion, depending on the interaction of severity and 
duration of ischemia. With acute flows below the threshold required for 
maintenance of basic housekeeping, injury in the core is established within a 
few minutes. During the subacute phase, the irreversible damage expands into the 
penumbra: multiple electrical and biological signals are triggered by 
periinfarct, spreading depression-like depolarizations leading to hypoxia and 
stepwise increase in lactate. Usually within 6 to 8 hours, all the penumbra are 
converted into irreversible infarcts. In a delayed phase, secondary phenomena 
may cause additional tissue damage: disruption of the tight junctions results in 
vasogenic edema, leading to increase of water content and damage expansion. 
Neutrophils and cytokinins cause secondary inflammation, inducing further damage 
in periinfarct regions and connecting fiber tracts. Multimodal imaging might be 
able to differentiate among the tissue compartments affected by acute, subacute, 
or delayed ischemic damage, and thereby might provide the basis for 
phase-specific treatment strategies.