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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Neural surface receptors integrate signals with diverse functions, such as neuronal injury and repair, and depending on pathophysiological context could have Janus-like roles in the ischaemic brain.
“Neural surface receptors integrate signals with diverse functions, such as neuronal injury and repair,96 which depending on the pathophysiological context could have Janus-like roles in the ischaemic brain.5,100”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [100]
In view of the Janus-like role of brain-repair signals for neuronal injury, initiating neurorestorative therapies in the very acute phase of stroke would probably induce more undesirable effects than treatment in the very late (chronic) phase.
“In view of the Janus-like role of brain-repair signals for neuronal injury,5,100 the initiation of neurorestorative therapies in the very acute phase of stroke would probably induce more undesirable effects than would treatment in the very late (chronic) phase.”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [100]
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- Authors
- Lo, E. H.
- Affiliations
- Harvard University (US)
- Corresponding author
- Lo, Eng H
- ORCID
- Lo, Eng H
- Venue
- Nature Medicine
- Published
- 2008-05
- Volume
- 14
- Issue
- 5
- Pages
- 497-500
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2011783556
- Cited by
- 611
- References
- 50
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 22 · 2023: 17 · 2022: 25 · 2021: 46 · 2020: 31 · 2019: 27 · 2018: 37 · 2017: 37 · 2016: 35 · 2015: 52 · 2014: 41 · 2013: 54 · 2012: 51
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- penumbra, stroke, focal cerebral ischemia, neurovascular remodeling, brain repair, ischemic injury, neuroimaging, therapeutic target
- MeSH terms
- Brain, Humans, Ischemia, Regional Blood Flow, Signal Transduction, Disease Progression, Stroke, Matrix Metalloproteinases
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