Evidence map›Paper›PMID 33892818›Full record

ArticleActa neuropathologica communications2021

Mild traumatic brain injury induces microvascular injury and accelerates Alzheimer-like pathogenesis in mice.

Yingxi Wu, Haijian Wu, Jianxiong Zeng, Brock Pluimer, Shirley Dong, Xiaochun Xie, Xinying Guo, Tenghuan Ge, Xinyan Liang, Sudi Feng and 6 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica communications, 2021. 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 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

48 citing papers in PubMed, 72 citations in OpenAlex.

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  7. Persistent dysmorphology and dysfunction of the brain microvasculature following repeated trauma.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 2 countries.

Yingxi Wu *Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Haijian Wu *Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Jianxiong ZengCenter for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Brock PluimerCenter for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Shirley DongCenter for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Xiaochun XieCenter for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Xinying GuoCenter for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Tenghuan GeCenter for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Xinyan LiangCenter for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Sudi FengCenter for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Youzhen YanCenter for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Jian-Fu ChenCenter for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, 90033, USA.
Naomi Sta MariaCenter for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.
Qingyi MaLawrence D. Longo, MD Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, 92350, USA.
Fernando Gomez-PinillaBrain Injury Research Center, Department of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Zhen ZhaoCenter for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA. zzhao@usc.edu.ORCID http://orcid.org/0000-0001-8967-5570
University of Southern California · USLoma Linda University · USUniversity of California, Los Angeles · US

Funding

A TIMEM252-dependent Microvascular Endophenotype in Alzheimer’s DiseaseRF1NS122060 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ZHAO, ZHEN · 2021 to 2021
$2.3M
Pericyte-neuronal crosstalk in health and Alzheimer's DiseaseR01AG061288 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ZHAO, ZHEN · 2019 to 2023
$2.1M
The protective effects of c-type natriuretic peptide in the neonatal brainR01NS112404 · NINDS · LOMA LINDA UNIVERSITY · PI MA, QINGYI · 2019 to 2023
$1.7M
Genetic interaction of PICALM and APOE in Alzheimer's diseaseR03AG063287 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ZHAO, ZHEN · 2019 to 2020
$330k
NIA NIH HHS R01 AG061288NIA NIH HHS R03 AG063287NINDS NIH HHS R01 NS112404NINDS NIH HHS R01NS112404NINDS NIH HHS RF1 NS122060NINDS NIH HHS RF1NS122060
6 · The paper itself

Abstract

introductionTraumatic brain injury (TBI) is considered as the most robust environmental risk factor for Alzheimer's disease (AD). Besides direct neuronal injury and neuroinflammation, vascular impairment is also a hallmark event of the pathological cascade after TBI. However, the vascular connection between TBI and subsequent AD pathogenesis remains underexplored.

methodsIn a closed-head mild TBI (mTBI) model in mice with controlled cortical impact, we examined the time courses of microvascular injury, blood-brain barrier (BBB) dysfunction, gliosis and motor function impairment in wild type C57BL/6 mice. We also evaluated the BBB integrity, amyloid pathology as well as cognitive functions after mTBI in the 5xFAD mouse model of AD.

resultsmTBI induced microvascular injury with BBB breakdown, pericyte loss, basement membrane alteration and cerebral blood flow reduction in mice, in which BBB breakdown preceded gliosis. More importantly, mTBI accelerated BBB leakage, amyloid pathology and cognitive impairment in the 5xFAD mice. DISCUSSION: Our data demonstrated that microvascular injury plays a key role in the pathogenesis of AD after mTBI. Therefore, restoring vascular functions might be beneficial for patients with mTBI, and potentially reduce the risk of developing AD.

Indexed as

Disease ProgressionAlzheimer DiseaseAnimalsBrain ConcussionCognitive DysfunctionHumansMiceMice, Inbred C57BLMice, TransgenicMicrovesselsAlzheimer’s diseaseBlood–brain barrierMicrovascular injuryTraumatic brain injuryβ-amyloid

Identifiers

PMID33892818
PMCPMC8063402
OpenAlexW3153773701

What OpenQuestion holds

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LicenceCC BY
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.