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A new penumbra: transitioning from injury into repair after stroke

Abstract

The penumbra is an area of brain tissue that is damaged but not yet dead after focal ischemia. The existence of a penumbra implies that therapeutic salvage is theoretically possible after stroke. The first decade of penumbral science investigated the ischemic regulation of electrophysiology, cerebral blood flow and metabolism. The second decade advanced our understanding of molecular mechanisms that mediate penumbral cell death. And the third decade saw the rapid development of clinical neuroimaging tools that are now increasingly applied in stroke patients. But how can we look ahead as we move into the fourth decade of penumbra research? This author speculates that a paradigm shift is needed. Most molecular targets for therapy have biphasic roles in stroke pathophysiology. During the acute phase, these targets mediate injury. During the recovery phase, the same mediators contribute to neurovascular remodeling. It is this boundary zone that comprises the new penumbra, and future investigations should dissect where, when and how damaged brain makes the transition from injury into repair.

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Figure 1: The penumbra.

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Acknowledgements

The speculative ideas presented here have come from innumerable stimulating discussions with many colleagues over the past few years, especially in the context of the stroke progress review group organized by the National Institute of Neurological Disorders and Stroke. I apologize to colleagues whose work could not be cited because of space limitations. Supported in part by a Bugher award from the American Heart Association and grants from the US National Institutes of Health.

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Lo, E. A new penumbra: transitioning from injury into repair after stroke. Nat Med 14, 497–500 (2008). https://doi.org/10.1038/nm1735

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