Evidence map›Paper›PMID 26813496›Full record

ArticleNature communications2016

Rapid endothelial cytoskeletal reorganization enables early blood-brain barrier disruption and long-term ischaemic reperfusion brain injury.

Yejie Shi, Lili Zhang, Hongjian Pu, Leilei Mao, Xiaoming Hu, Xiaoyan Jiang, Na Xu, R Anne Stetler, Feng Zhang, Xiangrong Liu and 4 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 262 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
262citing papers in PubMed, 1 pooled it
20.5field-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

262 citing papers in PubMed, 1 synthesis or guideline pooled it, 417 citations in OpenAlex.

  1. Pooled it
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  6. Temporal enhancement patterns on 3D-FLAIR MRI in labyrinthine infarction.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
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  12. Chemogenetic modulation of CNS pericytes: Impact on pericyte CaMolecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  13. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
  14. Article
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  19. Article
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202 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 2 countries.

Yejie ShiCenter of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.ORCID http://orcid.org/0000-0001-7502-9201
Lili ZhangCenter of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Hongjian PuCenter of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Leilei MaoCenter of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Xiaoming HuCenter of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Xiaoyan JiangCenter of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.ORCID http://orcid.org/0000-0003-3832-3756
Na XuState Key Laboratory of Medical Neurobiology, Institute of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
R Anne StetlerCenter of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Feng ZhangCenter of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Xiangrong LiuCenter of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Rehana K LeakDivision of Pharmaceutical Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, Pennsylvania 15282, USA.
Richard F KeepDepartment of Neurosurgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
Xunming JiChina-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
Jun ChenCenter of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
University of Pittsburgh · USCapital Medical University · CNDuquesne University · USFudan University · CNUniversity of Michigan · US

Funding

Neuroprotection in Models of Cerebral IschemiaR01NS045048 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHEN, JUN · 2003 to 2015
$3.1M
Mechanisms of Neurovascular Injury in Cerebral IschemiaR01NS089534 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHEN, JUN · 2014 to 2018
$1.7M
A novel mechanism of neurovascular protection in ischemic toleranceR01NS092810 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ZHANG, FENG · 2015 to 2020
$1.7M
Neuroprotective effect of HSP27 in Cerebral IschemiaR01NS056118 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHEN, JUN · 2006 to 2010
$1.5M
Heat shock proteins and neuroprotection in cerebral ischemiaI01BX002495 · VA · VETERANS HEALTH ADMINISTRATION · PI CHEN, JUN · 2015 to 2020
–
BLRD VA I01 BX002495NINDS NIH HHS NS045048NINDS NIH HHS NS056118NINDS NIH HHS NS089534NINDS NIH HHS NS092810NINDS NIH HHS R01 NS045048NINDS NIH HHS R01 NS056118NINDS NIH HHS R01 NS089534NINDS NIH HHS R01 NS092810
6 · The paper itself

Abstract

The mechanism and long-term consequences of early blood-brain barrier (BBB) disruption after cerebral ischaemic/reperfusion (I/R) injury are poorly understood. Here we discover that I/R induces subtle BBB leakage within 30-60 min, likely independent of gelatinase B/MMP-9 activities. The early BBB disruption is caused by the activation of ROCK/MLC signalling, persistent actin polymerization and the disassembly of junctional proteins within microvascular endothelial cells (ECs). Furthermore, the EC alterations facilitate subsequent infiltration of peripheral immune cells, including MMP-9-producing neutrophils/macrophages, resulting in late-onset, irreversible BBB damage. Inactivation of actin depolymerizing factor (ADF) causes sustained actin polymerization in ECs, whereas EC-targeted overexpression of constitutively active mutant ADF reduces actin polymerization and junctional protein disassembly, attenuates both early- and late-onset BBB impairment, and improves long-term histological and neurological outcomes. Thus, we identify a previously unexplored role for early BBB disruption in stroke outcomes, whereby BBB rupture may be a cause rather than a consequence of parenchymal cell injury.

Indexed as

ActinsAnimalsBlood-Brain BarrierBrain IschemiaCytoskeletonEndothelial CellsHumansMaleMatrix Metalloproteinase 9MicePolymerizationReperfusion InjuryActinsMatrix Metalloproteinase 9

Identifiers

PMID26813496
PMCPMC4737895
OpenAlexW2263957136

What OpenQuestion holds

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Registered trials

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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.