ReviewTranslational stroke research2023
Reinventing the Penumbra - the Emerging Clockwork of a Multi-modal Mechanistic Paradigm.
Review in Translational stroke research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Modulation of miRNAs by Phytochemicals in Cerebral Ischemia: A Systematic Review of In Vitro and In Vivo Studies.Phytotherapy research : PTR · 2025Pooled it
- Astrocytic Redox Homeostasis as a Metabolic Modulator of DNA Damage and Repair in the Ischemic Penumbra.Cells · 2026Review
- The hypoxia-inflammation cycle as a key mechanism of smoldering inflammation and progression in multiple sclerosis.Acta neuropathologica · 2026Review
- Ferroptosis induces heterogeneous death profiles that are controlled by lysosome rupture.Developmental cell · 2026Article
- Measuring cerebral glucose metabolism by chemical exchange-sensitive spin-lock (CESL) MRI of 2-deoxy-D-glucose in rodents.PloS one · 2026Article
- Aging Rewires Neuronal Metabolism, Exacerbating Cell Death After Ischemic Stroke: A Hidden Reason for the Failure of Neuroprotection.International journal of molecular sciences · 2025Article
- IGF2BP1 positively regulates CircOGDH accumulation in hypoxia induced stress granules.Acta pharmaceutica Sinica. B · 2025Article
- Statins in Acute Ischemic Stroke: Mechanisms, Resistance, and Precision Strategies for Neurovascular and Cognitive Protection.CNS drugs · 2025Review
- Microglial Autophagy and Mitophagy in Ischemic Stroke: From Dual Roles to Therapeutic Modulation.Biology · 2025Review
- Depth-Specific Hypoxic Responses to Spreading Depolarizations in Gyrencephalic Swine Cortex Unveiled by Photoacoustic Imaging.Translational stroke research · 2025Article
- Small Extracellular Vesicles From Hypoxia-Neuron Maintain Blood-Brain Barrier Integrity.Stroke · 2025Article
- The fuzzy MAD stroke conjecture, using Fuzzy C Means to classify multimodal apparent diffusion for ischemic stroke lesion stratification.Magnetic resonance imaging · 2025Article
- Early localization of tissue at risk for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: blood distribution on initial imaging vs early CT perfusion.Neurosurgical review · 2024Article
- Silymarin administration after cerebral ischemia improves survival of obese mice by increasing cortical BDNF and IGF1 levels.Frontiers in aging neuroscience · 2024Article
- Ischemic stroke-related gene expression profiles across species: a meta-analysis.Journal of inflammation (London, England) · 2023Article
- Perfusion Status in Lacunar Stroke: A Pathophysiological Issue.Diagnostics (Basel, Switzerland) · 2023Review
- Rectangular method: a modified technique for sampling the ischemic border zone in a rat model of transient middle cerebral artery occlusion.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2023Article
- Diagnostic biomarkers of ischemic stroke: strengths and limitations across blood, urine, and saliva.Frontiers in neurologyReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The concept of the ischemic penumbra was originally defined as the area around a necrotic stroke core and seen as the tissue at imminent risk of further damage. Today, the penumbra is generally considered as time-sensitive hypoperfused brain tissue with decreased oxygen and glucose availability, salvageable tissue as treated by intervention, and the potential target for neuroprotection in focal stroke. The original concept entailed electrical failure and potassium release but one short of neuronal cell death and was based on experimental stroke models, later confirmed in clinical imaging studies. However, even though the basic mechanisms have translated well, conferring brain protection, and improving neurological outcome after stroke based on the pathophysiological mechanisms in the penumbra has yet to be achieved. Recent findings shape the modern understanding of the penumbra revealing a plethora of molecular and cellular pathophysiological mechanisms. We now propose a new model of the penumbra, one which we hope will lay the foundation for future translational success. We focus on the availability of glucose, the brain's central source of energy, and bioenergetic failure as core pathophysiological concepts. We discuss the relation of mitochondrial function in different cell types to bioenergetics and apoptotic cell death mechanisms, autophagy, and neuroinflammation, to glucose metabolism in what is a dynamic ischemic penumbra.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.