Evidence map›Paper›PMID 27328690›Full record

ReviewJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2017

The continuum of spreading depolarizations in acute cortical lesion development: Examining Leão's legacy.

Jed A Hartings, C William Shuttleworth, Sergei A Kirov, Cenk Ayata, Jason M Hinzman, Brandon Foreman, R David Andrew, Martyn G Boutelle, K C Brennan, Andrew P Carlson and 24 more

Registry-linked trialOpen access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03321370 (Cortical Spreading Depolarization After Severe Traumatic Brain Injury), which is not on this map. Cited by 230 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
230citing papers in PubMed, 3 pooled it
20.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT03321370 recruitingnot on this mapstarted 2019, after this paper: background citation

Cortical Spreading Depolarization After Severe Traumatic Brain Injury

TypeobservationalSponsorHennepin County Medical Center, MinneapolisRan2019 to 2025Enrolled10ConditionsTraumatic Brain InjuryArmsContinuous electrocorticography post severe traumatic brain injury requiring neurosurgical intervention
3 · Its place in the literature

Who cites it

230 citing papers in PubMed, 3 syntheses or guidelines pooled it, 378 citations in OpenAlex.

  1. Pooled it
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  3. Systematic review of the pharmacological agents that have been tested against spreading depolarizations.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018
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  10. Spreading depolarization: A wave that precedes and drives cerebral ischemic cell death-Target for neuroprotection.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
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170 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

34 authors at 19 institutions in 8 countries.

Jed A Hartings1 Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
C William Shuttleworth3 Department of Neuroscience, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Sergei A Kirov4 Department of Neurosurgery and Brain and Behavior Discovery Institute, Medical College of Georgia, Augusta, GA, USA.
Cenk Ayata5 Neurovascular Research Unit, Department of Radiology, and Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Jason M Hinzman1 Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Brandon Foreman6 Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
R David Andrew7 Department of Biomedical & Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Martyn G Boutelle8 Department of Bioengineering, Imperial College London, London, United Kingdom.
K C Brennan9 Department of Neurology, University of Utah, Salt Lake City, UT, USA.
Andrew P Carlson11 Department of Neurosurgery, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Markus A Dahlem12 Department of Physics, Humboldt University of Berlin, Berlin, Germany.
Christoph Drenckhahn13 Department of Neurology, Charité University Medicine, Berlin, Germany.
Christian Dohmen14 Department of Neurology, University of Cologne, Cologne, Germany.
Martin Fabricius15 Department of Clinical Neurophysiology, Rigshospitalet, Glostrup, Denmark.
Eszter Farkas16 Department of Medical Physics and Informatics, Faculty of Medicine, and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.
Delphine Feuerstein17 Multimodal Imaging of Brain Metabolism, Max-Planck-Institute for Metabolism Research, Cologne, Germany.
Rudolf Graf17 Multimodal Imaging of Brain Metabolism, Max-Planck-Institute for Metabolism Research, Cologne, Germany.
Raimund Helbok18 Medical University of Innsbruck, Department of Neurology, Neurocritical Care Unit, Innsbruck, Austria.
Martin Lauritzen15 Department of Clinical Neurophysiology, Rigshospitalet, Glostrup, Denmark.
Sebastian Major13 Department of Neurology, Charité University Medicine, Berlin, Germany.
Ana I Oliveira-Ferreira20 Center for Stroke Research Berlin, Charité University Medicine, Berlin, Germany.
Frank Richter22 Institute of Physiology/Neurophysiology, Jena University Hospital, Jena, Germany.
Eric S Rosenthal5 Neurovascular Research Unit, Department of Radiology, and Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Oliver W Sakowitz23 Department of Neurosurgery, Klinikum Ludwigsburg, Ludwigsburg, Germany.
Renán Sánchez-Porras24 Department of Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany.
Edgar Santos24 Department of Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany.
Michael Schöll24 Department of Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany.
Anthony J Strong25 Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London.
Anja Urbach26 Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
M Brandon Westover5 Neurovascular Research Unit, Department of Radiology, and Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Maren Kl Winkler20 Center for Stroke Research Berlin, Charité University Medicine, Berlin, Germany.
Otto W Witte26 Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
Johannes Woitzik20 Center for Stroke Research Berlin, Charité University Medicine, Berlin, Germany.
Jens P Dreier13 Department of Neurology, Charité University Medicine, Berlin, Germany.
Charité - Universitätsmedizin Berlin · DEJena University Hospital · DEUniversity of Cincinnati Medical Center · USHarvard University · USHeidelberg University · DEMax Planck Institute for Metabolism Research · DERigshospitalet · DKUniversity Hospital Heidelberg · DEUniversity of New Mexico · USAugusta University · USHumboldt-Universität zu Berlin · DEImperial College London · GBKing's College London · GBMassachusetts General Hospital · USQueen's University · CAUniversität Innsbruck · ATUniversity of Cologne · DEUniversity of Szeged · HUUniversity of Utah · US

Funding

University of New Mexico (UNM) Center for Brain Recovery and RepairP20GM109089 · NIGMS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI CUNNINGHAM, LEE ANNA · 2015 to 2024
$22.7M
Synaptic Circuitry in StrokeR01NS083858 · NINDS · AUGUSTA UNIVERSITY · PI KIROV, SERGEI A · 2014 to 2022
$2.7M
Spreading Depolarizations and Post-Ischemic InjuryR01NS051288 · NINDS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI SHUTTLEWORTH, CLAUDE W · 2006 to 2014
$2.6M
Sensory plasticity in migraineR01NS085413 · NINDS · UNIVERSITY OF UTAH · PI BRENNAN, KEVIN CHRISTOPHER · 2013 to 2017
$1.7M
Quantitative Monitoring and Control of Sedation and Pain in the ICU EnvironmentK23NS090900 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI WESTOVER, MICHAEL BRANDON · 2014 to 2018
$988k
NIGMS NIH HHS P20 GM109089NINDS NIH HHS K23 NS090900NINDS NIH HHS R01 NS051288NINDS NIH HHS R01 NS083858NINDS NIH HHS R01 NS085413
6 · The paper itself

Abstract

A modern understanding of how cerebral cortical lesions develop after acute brain injury is based on Aristides Leão's historic discoveries of spreading depression and asphyxial/anoxic depolarization. Treated as separate entities for decades, we now appreciate that these events define a continuum of spreading mass depolarizations, a concept that is central to understanding their pathologic effects. Within minutes of acute severe ischemia, the onset of persistent depolarization triggers the breakdown of ion homeostasis and development of cytotoxic edema. These persistent changes are diagnosed as diffusion restriction in magnetic resonance imaging and define the ischemic core. In delayed lesion growth, transient spreading depolarizations arise spontaneously in the ischemic penumbra and induce further persistent depolarization and excitotoxic damage, progressively expanding the ischemic core. The causal role of these waves in lesion development has been proven by real-time monitoring of electrophysiology, blood flow, and cytotoxic edema. The spreading depolarization continuum further applies to other models of acute cortical lesions, suggesting that it is a universal principle of cortical lesion development. These pathophysiologic concepts establish a working hypothesis for translation to human disease, where complex patterns of depolarizations are observed in acute brain injury and appear to mediate and signal ongoing secondary damage.

Indexed as

Brain InjuriesCerebral CortexCerebrovascular CirculationCortical Spreading DepressionDiffusion Magnetic Resonance ImagingElectrocorticographyHumansbrain edemabrain ischemiabrain traumacardiac arrestcerebral blood flowcerebrovascular diseasediffusion weighted MRIelectrophysiologyfocal ischemiaglobal ischemianeurocritical careneuroprotectionneurovascular couplingselective neuronal deathSpreading depressionstrokesubarachnoid hemorrhagesystem biologytwo photon microscopyvasospasm

Identifiers

PMID27328690
PMCPMC5435288
OpenAlexW2471954838

What OpenQuestion holds

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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.