Evidence map›Paper›PMID 30996318›Full record

ArticleNature2019

Restoration of brain circulation and cellular functions hours post-mortem.

Zvonimir Vrselja, Stefano G Daniele, John Silbereis, Francesca Talpo, Yury M Morozov, André M M Sousa, Brian S Tanaka, Mario Skarica, Mihovil Pletikos, Navjot Kaur and 7 more

Open access · greenAbstract read
In one paragraph

Article in Nature, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.

0numbers the graph read from it
0cells of the map it votes in
108citing papers in PubMed
19.7field-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.

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

108 citing papers in PubMed, 302 citations in OpenAlex.

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  6. Experimenting with disembodied human brain might better approximate ground truth but could lack statistical assurance.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
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48 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 3 institutions in 2 countries.

Zvonimir Vrselja *Department of Neuroscience, Yale School of Medicine, New Haven, CT, USA.
Stefano G Daniele *Department of Neuroscience, Yale School of Medicine, New Haven, CT, USA.
John SilbereisDepartment of Neuroscience, Yale School of Medicine, New Haven, CT, USA.
Francesca TalpoDepartment of Neuroscience, Yale School of Medicine, New Haven, CT, USA.
Yury M MorozovDepartment of Neuroscience, Yale School of Medicine, New Haven, CT, USA.
André M M SousaDepartment of Neuroscience, Yale School of Medicine, New Haven, CT, USA.
Brian S TanakaCenter for Neuroscience and Regeneration Research, Yale School of Medicine, New Haven, CT, USA.
Mario SkaricaDepartment of Neuroscience, Yale School of Medicine, New Haven, CT, USA.
Mihovil PletikosDepartment of Neuroscience, Yale School of Medicine, New Haven, CT, USA.
Navjot KaurDepartment of Neuroscience, Yale School of Medicine, New Haven, CT, USA.
Zhen W ZhuangSection of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
Zhao LiuSection of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
Rafeed AlkawadriDepartment of Neurology, Yale School of Medicine, New Haven, CT, USA.
Albert J SinusasSection of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
Stephen R LathamInterdisciplinary Center for Bioethics, Yale University, New Haven, CT, USA.
Stephen G WaxmanCenter for Neuroscience and Regeneration Research, Yale School of Medicine, New Haven, CT, USA.
Nenad SestanDepartment of Neuroscience, Yale School of Medicine, New Haven, CT, USA. nenad.sestan@yale.edu.
Yale University · USUniversity of Pavia · ITUniversity of Pittsburgh · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9M
Yale Macaque Brain ResourceR01MH113257 · NIMH · YALE UNIVERSITY · PI Alvaro Duque · 2017 to 2026
$4.3M
Technology for functional study of cells and circuits in large postmortem brains ex vivoRF1MH117064 · NIMH · YALE UNIVERSITY · PI SESTAN, NENAD · 2018 to 2019
$3.0M
Ultra-high Performance MicroSPECT/CT systemS10OD021845 · OD · YALE UNIVERSITY · PI SINUSAS, ALBERT J · 2016 to 2016
$600k
NCATS NIH HHS UL1 TR001863NIGMS NIH HHS T32 GM007205NIH HHS S10 OD021845NIMH NIH HHS R01 MH113257NIMH NIH HHS RF1 MH117064
6 · The paper itself

Abstract

The brains of humans and other mammals are highly vulnerable to interruptions in blood flow and decreases in oxygen levels. Here we describe the restoration and maintenance of microcirculation and molecular and cellular functions of the intact pig brain under ex vivo normothermic conditions up to four hours post-mortem. We have developed an extracorporeal pulsatile-perfusion system and a haemoglobin-based, acellular, non-coagulative, echogenic, and cytoprotective perfusate that promotes recovery from anoxia, reduces reperfusion injury, prevents oedema, and metabolically supports the energy requirements of the brain. With this system, we observed preservation of cytoarchitecture; attenuation of cell death; and restoration of vascular dilatory and glial inflammatory responses, spontaneous synaptic activity, and active cerebral metabolism in the absence of global electrocorticographic activity. These findings demonstrate that under appropriate conditions the isolated, intact large mammalian brain possesses an underappreciated capacity for restoration of microcirculation and molecular and cellular activity after a prolonged post-mortem interval.

Indexed as

AutopsyCerebrovascular CirculationMicrocirculationSwineAnimalsBrainBrain IschemiaCaspase 3Cell SurvivalCerebral ArteriesDisease Models, AnimalHypoxia, BrainInflammationNeurogliaNeuronsPerfusionCaspase 3

Identifiers

PMID30996318
PMCPMC6844189
OpenAlexW2939414360

What OpenQuestion holds

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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.