Evidence map›Paper›PMID 34545550›Full record

ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2021

Upregulation of AQP4 Improves Blood-Brain Barrier Integrity and Perihematomal Edema Following Intracerebral Hemorrhage.

Hanwool Jeon, Moinay Kim, Wonhyoung Park, Joon Seo Lim, Eunyeup Lee, Hyeuk Cha, Jae Sung Ahn, Jeong Hoon Kim, Seok Ho Hong, Ji Eun Park and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
5.2field-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

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.

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  20. New targets in spontaneous intracerebral hemorrhage.Current opinion in neurology · 2025
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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

13 authors at 1 institution in 1 country.

Hanwool Jeon *Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Moinay Kim *Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Wonhyoung Park *Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Joon Seo Lim *Clinical Research Center, Asan Medical Center, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Eunyeup LeeDepartment of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Hyeuk ChaDepartment of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Jae Sung Ahn *Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Jeong Hoon Kim *Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Seok Ho Hong *Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Ji Eun ParkUniversity of Ulsan College of Medicine, Seoul, Republic of Korea.
Eun-Jae LeeDepartment of Medical Science, Asan Medical Center, Asan Medical Institute of Convergence Science and Technology, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Chul-Woong WooConvergence Medicine Research Center, Asan Medical Center, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Seungjoo LeeDepartment of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. changhill@gmail.com.ORCID http://orcid.org/0000-0003-0641-3917
Ulsan College · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In intracerebral hemorrhage (ICH), delayed secondary neural damages largely occur from perihematomal edema (PHE) resulting from the disruption of the blood-brain barrier (BBB). PHE is often considered the principal cause of morbidity and mortality in patients with ICH. Nevertheless, the main cellular mechanism as well as the specific BBB component involved in the formation of PHE after ICH remains elusive. Herein, we evaluated the role of AQP4, a water channel expressed on the astrocytes of the BBB, in the formation of PHE in ICH. The static and dynamic functions of the BBB were evaluated by analyzing the microstructure and leakage assay. Protein changes in the PHE lesion were analyzed and the control mechanism of AQP4 expression by reactive oxygen species was also investigated. Delayed PHE formation due to BBB disruption after ICH was confirmed by the decreased coverage of multiple BBB components and increased dynamic leakages. Microstructure assay showed that among the BBB components, AQP4 showed a markedly decreased expression in the PHE lesions. The decrease in AQP4 was due to microenvironmental ROS derived from the hemorrhage and was restored by treatment with ROS scavenger. AQP4-deficient mice had significantly larger PHE lesions and unfavorable survival outcomes compared with wild-type mice. Our data identify AQP4 as a specific BBB-modulating target for alleviating PHE in ICH. Further comprehensive studies are needed to form the preclinical basis for the use of AQP4 enhancers as BBB modulators for preventing delayed cerebral edema after ICH.

Indexed as

Aquaporin 4Blood-Brain BarrierAnimalsCerebral HemorrhageEdemaHumansMiceUp-RegulationAquaporin 4Intracerebral hemorrhagePerihematomal edemaVascular biologyVasogenic edema

Identifiers

PMID34545550
PMCPMC8804112
OpenAlexW3199243439

What OpenQuestion holds

Textmetadata
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.