15 - The ischemic penumbra: the evolution of a concept

Summary

Definition

In human ischemic stroke the affected brain tissue has metabolic requirements that can no longer be supported by a sudden interruption, or at least reduction, in nutrient supply and waste disposal resulting from disease in a proximal artery. The underlying pathophysiological changes immediately following arterial occlusion include an initial loss of neuronal electrical activity followed by depletion of cellular energy stores and the loss of the transmembrane ion pumps which maintain water, sodium, chloride and potassium balance. Cellular necrosis will follow these changes if the cell's minimum energy requirements are not met. The tissue supplied by the artery is not affected homogeneously by this process, and critical blood flow thresholds associated with irreversible tissue infarction, functional tissue impairment, or benign oligemia can be identified. Several methods of threshold detection using modern imaging techniques lead to differing interpretations of this in vivo, and the extensive molecular and biochemical mechanisms in the penumbra can only partially be evaluated in human stroke patients. The region of incomplete ischemia in stroke usually adjacent to the area of profound ischemia has been termed the ischemic penumbra. A useful functional definition of the penumbra is that region of under-perfused brain tissue that is metabolically impaired, classically showing electrical inactivity, but with cellular morphology intact. In humans, this region is closely associated with established critical thresholds for blood flow rates using positron emission tomography (PET).