Evidence map›Paper›PMID 31820363›Full record

ReviewGeroScience2020

Direct electrophysiological evidence that spreading depolarization-induced spreading depression is the pathophysiological correlate of the migraine aura and a review of the spreading depolarization continuum of acute neuronal mass injury.

Sebastian Major, Shufan Huo, Coline L Lemale, Eberhard Siebert, Denny Milakara, Johannes Woitzik, Karen Gertz, Jens P Dreier

Open access · bronzeAbstract readReview
In one paragraph

Review in GeroScience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 2 pooled it
5.4field-weighted citation impact, top 4% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 75 citations in OpenAlex.

  1. What does a migraine aura look like?-A systematic review.The journal of headache and pain · 2025
    Pooled it
  2. Pooled it
  3. Hemiplegic migraine: genetics and pathophysiology.The Journal of clinical investigation · 2026
    Review
  4. Article
  5. 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
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  20. Cortical spreading depolarization-induced constriction of penetrating arteries can cause watershed ischemia: A potential mechanism for white matter lesions.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023
    Article
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

8 authors at 3 institutions in 1 country.

Sebastian MajorCenter for Stroke Research, Campus Charité Mitte, Charité University Medicine Berlin, Charitéplatz 1, 10117, Berlin, Germany.ORCID https://orcid.org/0000-0003-0970-1308
Shufan HuoCenter for Stroke Research, Campus Charité Mitte, Charité University Medicine Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Coline L LemaleCenter for Stroke Research, Campus Charité Mitte, Charité University Medicine Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Eberhard SiebertDepartment of Neuroradiology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Denny MilakaraSolution Centre for Image Guided Local Therapies (STIMULATE), Otto-von-Guericke-University, Magdeburg, Germany.
Johannes WoitzikEvangelisches Krankenhaus Oldenburg, University of Oldenburg, Oldenburg, Germany.
Karen GertzCenter for Stroke Research, Campus Charité Mitte, Charité University Medicine Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Jens P DreierCenter for Stroke Research, Campus Charité Mitte, Charité University Medicine Berlin, Charitéplatz 1, 10117, Berlin, Germany. jens.dreier@charite.de.ORCID https://orcid.org/0000-0001-7459-2828
Humboldt-Universität zu Berlin · DECarl von Ossietzky Universität Oldenburg · DEOtto-von-Guericke-Universität Magdeburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Spreading depolarization is observed as a large negative shift of the direct current potential, swelling of neuronal somas, and dendritic beading in the brain's gray matter and represents a state of a potentially reversible mass injury. Its hallmark is the abrupt, massive ion translocation between intraneuronal and extracellular compartment that causes water uptake (= cytotoxic edema) and massive glutamate release. Dependent on the tissue's energy status, spreading depolarization can co-occur with different depression or silencing patterns of spontaneous activity. In adequately supplied tissue, spreading depolarization induces spreading depression of activity. In severely ischemic tissue, nonspreading depression of activity precedes spreading depolarization. The depression pattern determines the neurological deficit which is either spreading such as in migraine aura or migraine stroke or nonspreading such as in transient ischemic attack or typical stroke. Although a clinical distinction between spreading and nonspreading focal neurological deficits is useful because they are associated with different probabilities of permanent damage, it is important to note that spreading depolarization, the neuronal injury potential, occurs in all of these conditions. Here, we first review the scientific basis of the continuum of spreading depolarizations. Second, we highlight the transition zone of the continuum from reversibility to irreversibility using clinical cases of aneurysmal subarachnoid hemorrhage and cerebral amyloid angiopathy. These illustrate how modern neuroimaging and neuromonitoring technologies increasingly bridge the gap between basic sciences and clinic. For example, we provide direct electrophysiological evidence for the first time that spreading depolarization-induced spreading depression is the pathophysiological correlate of the migraine aura.

Indexed as

Cortical Spreading DepressionEpilepsyMigraine DisordersStrokeHumansNeuronsCerebral amyloid angiopathyDelayed cerebral ischemiaMigraine auraSpreading depressionSubarachnoid hemorrhage

Identifiers

PMID31820363
PMCPMC7031471
OpenAlexW2992454104

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.