In the core zone, which is an area of severe ischemia (blood flow below 10% to 25%), the loss of inadequate supply of oxygen and glucose results in rapid depletion of energy stores.  Severe ischemia can result in necrosis of neurons and also of supporting cellular elements (glial cells) within the severely ischemic area.

Brain cells within the penumbra, a rim of mild to moderately ischemic tissue lying between tissue that is normally perfused and the area in which infarction is evolving, may remain viable for several hours.  That is because the penumbral zone is supplied with blood by collateral arteries anastomosing with branches of the occluded vascular tree (see inset).  However, even cells in this region will die if reperfusion is not established during the early hours since collateral circulation is inadequate to maintain the neuronal demand for oxygen and glucose indefinitely.

In this example, the ischemic penumbra is shown as a rim of tissue surrounding the severely ischemic core lying within the vascular territory of the pre-Rolandic branch of the left middle cerebral artery.  The Rolandic artery is occluded by a thromboembolus.  The extent of the penumbra varies directly with the number and patency of collateral arteries.

The penumbra is where pharmacologic interventions are most likely to be effective.  However, it may also be possible to salvage cells within the severely ischemic core zone.  Although severe ischemia kills selectively vulnerable neurons, glial cells may be spared if blood flow is restored early.  Therefore, timely recanalization of the occluded vessel should theoretically restore perfusion in both the penumbra and in the severely ischemic core.  Partial recanalization should markedly reduce the size of the penumbra as well.