Evidence map›Paper›PMID 41673123›Full record

ArticleScientific reports2026

The metabolic consequences of evoked spreading depolarization in brain slices.

Olivia Grech, Caroline Mugo, Lisa J Hill, Samuel R Heaselgrave, Zerin Alimajstorovic, Andreas Yiangou, Hannah S Lyons, James Mitchell, Gareth G Lavery, Daniel Fulton and 1 more

Abstract read
In one paragraph

Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Thirty years later: Revisiting the glial failure hypothesis as the homeostatic organizing principle of ischemic injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
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

11 authors.

Olivia GrechMetabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK.
Caroline MugoMetabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK.
Lisa J HillBiomedical Sciences, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK.
Samuel R HeaselgraveCenter of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390- 9077, USA.
Zerin AlimajstorovicMetabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK.
Andreas YiangouMetabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK.
Hannah S LyonsMetabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK.
James MitchellMetabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK.
Gareth G LaveryCentre for Systems Health and Integrated Metabolic Research, Department of Biosciences, School of Science and Technology, Nottingham Trent University, Clifton Campus, Nottingham, NG11 8NS, UK.
Daniel FultonDepartment of Inflammation and Ageing, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK.
Alexandra J SinclairMetabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, B15 2TT, UK. a.b.sinclair@bham.ac.uk.

Funding

Association of British Neurologists and Guarantors of the Brain FellowshipSir Jules Thorn Charitable Trust Award for Biomedical Research
6 · The paper itself

Abstract

Spreading depolarization is a wave of neuronal and glial depolarization that propagates through brain tissue, triggering neuropeptide release and altered blood flow. It has been observed in ischemic stroke, traumatic brain injury, subarachnoid haemorrhage, epilepsy, and migraine aura. Spreading depolarization imposes a high energetic demand, and recovery impaired under metabolic substrate deficiency. Despite its clinical relevance, metabolic responses remain poorly understood, limiting therapeutic progress. We investigated metabolic effects of spreading depolarisation using an ex vivo brain slice model, aiming to characterise changes in intracellular calcium signalling, mitochondrial function, and central carbon metabolism, and to assess the impact of glucose deprivation. We further tested whether coenzyme Q10 could improve recovery under metabolically compromised conditions. Spreading depolarization increased mitochondrial activity and shifted metabolism toward anaerobic respiration and glycolysis. Glucose deprivation impaired recovery, inducing mitochondrial dysfunction and accumulation intermediates indicative of tricarboxylic acid cycle stalling and disrupted central carbon metabolism. Supplementing glucose-deprived brain slices with coenzyme Q10 shortened spreading depolarization repolarization duration, indicating enhanced metabolic recovery. These findings demonstrate that spreading depolarization imposes a significant metabolic burden, particularly under glucose limitation, and that mitochondrial-targeted interventions such as coenzyme Q10 may enhance tissue resilience in neurological disorders.

Indexed as

BrainCortical Spreading DepressionAnimalsCalcium SignalingCarbonEnergy MetabolismGlucoseGlycolysisMaleMitochondriaNeuronsUbiquinoneCarboncoenzyme Q10GlucoseUbiquinoneCentral carbon metabolismCoenzyme Q10Glucose deprivationMitochondrial functionMulti electrode arraySpreading depolarization

Identifiers

PMID41673123
PMCPMC12972070

What OpenQuestion holds

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LicenceCC BY
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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.