Evidence map›Paper›PMID 29460006›Full record

ArticleActa neuropathologica2018

Mechanical disruption of the blood-brain barrier following experimental concussion.

Victoria E Johnson, Maura T Weber, Rui Xiao, D Kacy Cullen, David F Meaney, William Stewart, Douglas H Smith

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed, 2 pooled it
13.5field-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

103 citing papers in PubMed, 2 syntheses or guidelines pooled it, 156 citations in OpenAlex.

  1. Pooled it
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  6. Traumatic Microhemorrhages Are Not Synonymous With Axonal Injury.Annals of clinical and translational neurology · 2026
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43 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Victoria E JohnsonDepartment of Neurosurgery, Penn Center for Brain Injury and Repair, Perelman School of Medicine, University of Pennsylvania, 105 Hayden Hall, 3320 Smith Walk, Philadelphia, PA, 19104, USA.
Maura T WeberDepartment of Neurosurgery, Penn Center for Brain Injury and Repair, Perelman School of Medicine, University of Pennsylvania, 105 Hayden Hall, 3320 Smith Walk, Philadelphia, PA, 19104, USA.
Rui XiaoThe Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, 19104, USA.
D Kacy CullenDepartment of Neurosurgery, Penn Center for Brain Injury and Repair, Perelman School of Medicine, University of Pennsylvania, 105 Hayden Hall, 3320 Smith Walk, Philadelphia, PA, 19104, USA.
David F MeaneyDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA.
William StewartDepartment of Neuropathology, Queen Elizabeth University Hospital, Glasgow, G51 4TF, UK.
Douglas H SmithDepartment of Neurosurgery, Penn Center for Brain Injury and Repair, Perelman School of Medicine, University of Pennsylvania, 105 Hayden Hall, 3320 Smith Walk, Philadelphia, PA, 19104, USA. smithdou@pennmedicine.upenn.edu.
University of Pennsylvania · USUniversity of Glasgow · GB

Funding

TBI: Uncovering Mechanisms of AD-like pathologyR01NS038104 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI SMITH, DOUGLAS HAMILTON · 1999 to 2020
$7.6M
Neuropathological Characterization of 'CTE'R01NS094003 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI Douglas Hamilton Smith, William Stewart · 2016 to 2026
$5.1M
Detection and Mechanisms of Mild Traumatic Brain InjuryR01NS092398 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI SMITH, DOUGLAS HAMILTON · 2015 to 2019
$1.9M
Uncovering mechanical mechanisms of traumatic axonal injuryR01EB021293 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI SHENOY, VIVEK, SMITH, DOUGLAS HAMILTON · 2016 to 2019
$1.4M
Chronic neurodegenerative and neurophysiological sequela of closed-head TBII01RX001097 · VA · PHILADELPHIA VA MEDICAL CENTER · PI DUDA, JOHN ERIC · 2015 to 2018
–
NIBIB NIH HHS R01 EB021293NINDS NIH HHS R01 NS038104NINDS NIH HHS R01NS038104NINDS NIH HHS R01 NS092398NINDS NIH HHS R01NS092398NINDS NIH HHS R01 NS094003NINDS NIH HHS R01NS094003RRD VA I01 RX001097
6 · The paper itself

Abstract

Although concussion is now recognized as a major health issue, its non-lethal nature has limited characterization of the underlying pathophysiology. In particular, potential neuropathological changes have typically been inferred from non-invasive techniques or post-mortem examinations of severe traumatic brain injury (TBI). Here, we used a swine model of head rotational acceleration based on human concussion to examine blood-brain barrier (BBB) integrity after injury in association with diffuse axonal injury and glial responses. We then determined the potential clinical relevance of the swine concussion findings through comparisons with pathological changes in human severe TBI, where post-mortem examinations are possible. At 6-72 h post-injury in swine, we observed multifocal disruption of the BBB, demonstrated by extravasation of serum proteins, fibrinogen and immunoglobulin-G, in the absence of hemorrhage or other focal pathology. BBB disruption was observed in a stereotyped distribution consistent with biomechanical insult. Specifically, extravasated serum proteins were frequently observed at interfaces between regions of tissue with differing material properties, including the gray-white boundary, periventricular and subpial regions. In addition, there was substantial overlap of BBB disruption with regions of axonal pathology in the white matter. Acute perivascular cellular uptake of blood-borne proteins was observed to be prominent in astrocytes (GFAP-positive) and neurons (MAP-2-positive), but not microglia (IBA1-positive). Parallel examination of human severe TBI revealed similar patterns of serum extravasation and glial uptake of serum proteins, but to a much greater extent than in the swine model, attributed to the higher injury severity. These data suggest that BBB disruption represents a new and important pathological feature of concussion.

Indexed as

AdolescentAdultAnimalsAstrocytesBiomarkersBiomechanical PhenomenaBlood-Brain BarrierBrain ConcussionCapillary PermeabilityDisease Models, AnimalFemaleHumansMaleMiddle AgedSwineSwine, MiniatureBiomarkersBiomechanicsBlood–brain barrierConcussionFibrinogenGliosisMild traumatic brain injury

Identifiers

PMID29460006
PMCPMC6532777
OpenAlexW2787895993

What OpenQuestion holds

Textmetadata
LicenceTDM
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.