Heterogeneity in the penumbra

Original experimental studies in nonhuman primate models of focal ischemia showed flow-related changes in evoked potentials that suggested a circumferential zone of low regional cerebral blood flow with normal K+ homeostasis, around a core of permanent injury in the striatum or the cortex. This became the basis for the definition of the ischemic penumbra. Imaging techniques of the time suggested a homogeneous core of injury, while positing a surrounding ‘penumbral’ region that could be salvaged. However, both molecular studies and observations of vascular integrity indicate a more complex and dynamic situation in the ischemic core that also changes with time. The microvascular, cellular, and molecular events in the acute setting are compatible with heterogeneity of the injury within the injury center, which at early time points can be described as multiple ‘mini-cores' associated with multiple ‘mini-penumbras’. These observations suggest the progression of injury from many small foci to a homogeneous defect over time after the onset of ischemia. Recent observations with updated imaging techniques and data processing support these dynamic changes within the core and the penumbra in humans following focal ischemia.