Evidence map›Paper›PMID 25424475›Full record

ArticleStroke2015

Brain cell death is reduced with cooling by 3.5°C to 5°C but increased with cooling by 8.5°C in a piglet asphyxia model.

Daniel Alonso-Alconada, Kevin D Broad, Alan Bainbridge, Manigandan Chandrasekaran, Stuart D Faulkner, Áron Kerenyi, Jane Hassell, Eridan Rocha-Ferreira, Mariya Hristova, Bobbi Fleiss and 6 more

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In one paragraph

Article in Stroke, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 1 pooled it
–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

58 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  5. Review
  6. Stay cool and keep moving forwards.Pediatric research · 2025
    Article
  7. Article
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  9. Article
  10. SMYD5 is a regulator of the mild hypothermia response.bioRxiv : the preprint server for biology · 2024
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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

16 authors.

Daniel Alonso-AlconadaFrom the Institute for Women's Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King's College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United Kingdom (X.G.).
Kevin D BroadFrom the Institute for Women's Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King's College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United Kingdom (X.G.).
Alan BainbridgeFrom the Institute for Women's Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King's College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United Kingdom (X.G.).
Manigandan ChandrasekaranFrom the Institute for Women's Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King's College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United Kingdom (X.G.).
Stuart D FaulknerFrom the Institute for Women's Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King's College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United Kingdom (X.G.).
Áron KerenyiFrom the Institute for Women's Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King's College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United Kingdom (X.G.).
Jane HassellFrom the Institute for Women's Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King's College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United Kingdom (X.G.).
Eridan Rocha-FerreiraFrom the Institute for Women's Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King's College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United Kingdom (X.G.).
Mariya HristovaFrom the Institute for Women's Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King's College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United Kingdom (X.G.).
Bobbi FleissFrom the Institute for Women's Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King's College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United Kingdom (X.G.).
Kate BennettFrom the Institute for Women's Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King's College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United Kingdom (X.G.).
Dorottya KelenFrom the Institute for Women's Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King's College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United Kingdom (X.G.).
Ernest CadyFrom the Institute for Women's Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King's College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United Kingdom (X.G.).
Pierre GressensFrom the Institute for Women's Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King's College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United Kingdom (X.G.).
Xavier GolayFrom the Institute for Women's Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King's College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United Kingdom (X.G.).
Nicola J RobertsonFrom the Institute for Women's Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King's College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United Kingdom (X.G.). n.robertson@ucl.ac.uk.

Funding

Medical Research Council G0501259
6 · The paper itself

Abstract

background and purposeIn infants with moderate to severe neonatal encephalopathy, whole-body cooling at 33°C to 34°C for 72 hours is standard care with a number needed to treat to prevent a adverse outcome of 6 to 7. The precise brain temperature providing optimal neuroprotection is unknown.

methodsAfter a quantified global cerebral hypoxic-ischemic insult, 28 piglets aged <24 hours were randomized (each group, n=7) to (1) normothermia (38.5°C throughout) or whole-body cooling 2 to 26 hours after insult to (2) 35°C, (3) 33.5°C, or (4) 30°C. At 48 hours after hypoxia-ischemia, delayed cell death (terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling and cleaved caspase 3) and microglial ramification (ionized calcium-binding adapter molecule 1) were evaluated.

resultsAt 48 hours after hypoxia-ischemia, substantial cerebral injury was found in the normothermia and 30°C hypothermia groups. However, with 35°C and 33.5°C cooling, a clear reduction in delayed cell death and microglial activation was observed in most brain regions (P<0.05), with no differences between 35°C and 33.5°C cooling groups. A protective pattern was observed, with U-shaped temperature dependence in delayed cell death in periventricular white matter, caudate nucleus, putamen, hippocampus, and thalamus. A microglial activation pattern was also seen, with inverted U-shaped temperature dependence in periventricular white matter, caudate nucleus, internal capsule, and hippocampus (all P<0.05).

conclusionsCooling to 35°C (an absolute drop of 3.5°C as in therapeutic hypothermia protocols) or to 33.5°C provided protection in most brain regions after a cerebral hypoxic-ischemic insult in the newborn piglet. Although the relatively wide therapeutic range of a 3.5°C to 5°C drop in temperature reassured, overcooling (an 8.5°C drop) was clearly detrimental in some brain regions.

Indexed as

AnimalsAsphyxiaBrainCaudate NucleusCell DeathCell SurvivalDisease Models, AnimalHippocampusHypothermia, InducedHypoxia-Ischemia, BrainPutamenSwineThalamusWhite Matterhypothermiahypoxia-ischemia, brainneonatal encephalopathyneuroprotection

Identifiers

PMID25424475
PMCPMC4276417

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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.