Evidence map›Paper›PMID 33203936›Full record

ArticleCellular & molecular immunology2021

Targeting the CD146/Galectin-9 axis protects the integrity of the blood-brain barrier in experimental cerebral malaria.

Hongxia Duan, Shuai Zhao, Jianquan Xiang, Chenhui Ju, Xuehui Chen, Irene Gramaglia, Xiyun Yan

Open access · hybridAbstract read
In one paragraph

Article in Cellular & molecular immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

21 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Galectin-9-An Emerging Glyco-Immune Checkpoint Target for Cancer Therapy.International journal of molecular sciences · 2025
    Review
  5. Article
  6. The blood-brain barrier: a help and a hindrance.Brain : a journal of neurology · 2025
    Review
  7. Article
  8. Article
  9. Review
  10. CD8CNS neuroscience & therapeutics · 2024
    Article
  11. Review
  12. A subpopulation of CD146Cellular & molecular immunology · 2023
    Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. MeningiticFrontiers in cellular neuroscience · 2022
    Article
  19. Article
  20. Article
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

7 authors at 2 institutions in 1 country.

Hongxia Duan *Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. cherryshoen@ibp.ac.cn.ORCID http://orcid.org/0000-0003-3995-1228
Shuai Zhao *Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.ORCID http://orcid.org/0000-0002-1488-2601
Jianquan Xiang *Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Chenhui JuKey Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Xuehui ChenKey Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Irene GramagliaLa Jolla Infectious Disease Institute, San Diego, CA, USA.
Xiyun YanKey Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. yanxy@ibp.ac.cn.
Chinese Academy of Sciences · CNSouthwest Medical University · CN

Funding

National Natural Science Foundation of China (National Science Foundation of China) 31530026National Natural Science Foundation of China (National Science Foundation of China) 31770793Natural Science Foundation of Beijing Municipality (Beijing Natural Science Foundation) 7192123
6 · The paper itself

Abstract

Cerebral malaria (CM) is a life-threatening diffuse encephalopathy caused by Plasmodium falciparum, in which the destruction of the blood-brain barrier (BBB) is the main cause of death. However, increasing evidence has shown that antimalarial drugs, the current treatment for CM, do little to protect against CM-induced BBB damage. Therefore, a means to alleviate BBB dysfunction would be a promising adjuvant therapy for CM. The adhesion molecule CD146 has been reported to be expressed in both endothelial cells and proinflammatory immune cells and mediates neuroinflammation. Here, we demonstrate that CD146 expressed on BBB endothelial cells but not immune cells is a novel therapeutic target in a mouse model of experimental cerebral malaria (eCM). Endothelial CD146 is upregulated during eCM development and facilitates the sequestration of infected red blood cells (RBCs) and/or proinflammatory lymphocytes in CNS blood vessels, thereby promoting the disruption of BBB integrity. Mechanistic studies showed that the interaction of CD146 and Galectin-9 contributes to the aggregation of infected RBCs and lymphocytes. Deletion of endothelial CD146 or treatment with the anti-CD146 antibody AA98 prevents severe signs of eCM, such as limb paralysis, brain vascular leakage, and death. In addition, AA98 combined with the antiparasitic drug artemether improved the cognition and memory of mice with eCM. Taken together, our findings suggest that endothelial CD146 is a novel and promising target in combination with antiparasitic drugs for future CM therapies.

Indexed as

Blood-Brain BarrierCD146 AntigenMalaria, CerebralAnimalsDisease Models, AnimalEndothelial CellsGalectinsMiceCD146 AntigenGalectinsMcam protein, mouseBBBCD146experimental cerebral malaria

Identifiers

PMID33203936
PMCPMC8484550
OpenAlexW3101681795

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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.