Table 1.

The three phases of infarct progression.

Phases	Cerebral Blood Flow Threshold	Mechanisms of Damage
Acute phase (few minutes from ischemia onset)	<20% of pre-occlusion values (core)	Ischemia-induced energy failure and terminal depolarization of cell membranes
Subacute phase (from 4–6 h to >24 h in different models)	25 and 50% of pre-occlusion values (penumbra)	The irreversible damage expands into the areas around the core until after several hours, so the core expands into the penumbra, defined as areas of decreased CBF and O2 metabolism, but increased OEF. The main mechanism is periinfarct spreading depression, which starts at the border of the infarct core and spreads over the ipsilateral hemisphere. The metabolic rate of the tissue but not rCBF markedly increases, leading to stepwise accumulation of lactate with each depolarization, loss of ionic gradients, until cell death.
Delayed phase (several days or even weeks)	25 and 50% of pre-occlusion values (penumbra)	Secondary phenomena (vasogenic edema, inflammation, programmed cell death) may contribute to further progression of tissue damage

CBF: cerebral blood flow; OEF: oxygen extraction fraction.