The ischaemic penumbra: twenty years on.

In focal ischaemia, the penumbra defines regions with blood flow below that needed to sustain electrical activity, but above that required to maintain cellular ionic gradients, and that lead in time to infarction. Among other terms used to describe regions surrounding the ischaemic core, "penumbra" is the only one based on a precise functional state of partially ischaemic tissue. The precarious balance between energy supply and demand that characterizes the penumbra and the proximity of the ischaemic core are the basis of a number of important features: (a) It is a time-limited condition, with a tendency to evolve towards infarction and to propagate to adjacent viable tissue; (b) "misery perfusion" is associated with increased oxygen extraction, acidosis, and high glucose utilization, but residual ATP; (c) recurrent spreading depression contributes to the deterioration of the penumbra, at least in animal models of stroke; (d) there is no sustained increase of extracellular glutamate; and (e) improvement of local perfusion and reduction of energy demand remain the most rational approaches to rescue the penumbra. By defining a window of opportunity for therapeutic intervention in stroke, the concept of ischaemic penumbra has enormously stimulated research in this field and led to a better understanding of the pathophysiology of cerebral ischaemia, with direct practical application for the surgical management of cerebrovascular disorders such as aneurysms.