Evidence map›Paper›PMID 40426195›Full record

ArticleJournal of neuroinflammation2025

Endothelial TREM-1 mediates sepsis-induced blood‒brain barrier disruption and cognitive impairment via the PI3K/Akt pathway.

Yuwen Su, Wanwan Zhu, Tong Su, Lian Huang, Mubing Qin, Qingyu Wang, Qi Xu, Yi Li, Jianbo Xiu

Abstract read
In one paragraph

Article in Journal of neuroinflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

10 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
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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

9 authors.

Yuwen Su *State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, School of Basic Medicine Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China.
Wanwan Zhu *State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, School of Basic Medicine Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China.
Tong SuState Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, School of Basic Medicine Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China.
Lian HuangState Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, School of Basic Medicine Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China.
Mubing QinEmergency Department, The State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.
Qingyu WangState Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, School of Basic Medicine Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China.
Qi XuState Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, School of Basic Medicine Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China. xuqi@pumc.edu.cn.
Yi LiEmergency Department, The State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China. billliyi@126.com.
Jianbo XiuState Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, School of Basic Medicine Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China. xiujianbo@ibms.cams.cn.

Funding

CAMS Innovation Fund for Medical Sciences 2021-I2M-1-020National High Level Hospital Clinical Research Funding 2022-PUMCH-B-109Research grants from STI2030-Major Projects 2021ZD0203001Research grants from STI2030-Major Projects 2022ZD0211701Special Research Fund for Central Universities, Peking Union Medical College 3332024120
6 · The paper itself

Abstract

The blood‒brain barrier (BBB) is a critical selective interface between the central nervous system (CNS) and the blood circulation. BBB dysfunction plays an important role in the neurological damage caused by sepsis. However, the mechanisms underlying the disruption of the BBB during sepsis remain unclear. We established a human induced pluripotent stem cell (iPSC)-derived BBB model and reported that treating with sepsis patient serum leads to structural and functional disruption of the BBB. In a cecal ligation and puncture (CLP)-induced mouse model of sepsis, we also observed disruption of the BBB, inflammation in the brain, and impairments in cognition. In both models, we found that the expression of TREM-1 was significantly increased in endothelial cells. TREM-1 knockout specifically in endothelial cells alleviated BBB dysfunction and cognitive impairments. Further study revealed that TREM-1 affects the expression of genes involved in the PI3K/Akt signaling pathway. The protective effects of TREM-1 inhibition on the BBB and cognition were abrogated by PI3K inhibitors. Our findings suggest that endothelial TREM-1 induces sepsis-induced BBB disruption and cognitive impairments via the PI3K/Akt signaling pathway. Targeting endothelial TREM-1 or the PI3K/Akt signaling pathway may be a promising strategy to maintain BBB integrity and improve cognitive function in sepsis patients.

Indexed as

Blood-Brain BarrierCognitive DysfunctionEndothelial CellsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSepsisTriggering Receptor Expressed on Myeloid Cells-1AnimalsHumansInduced Pluripotent Stem CellsMaleMiceMice, Inbred C57BLMice, KnockoutSignal TransductionPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTREM1 protein, mouseTriggering Receptor Expressed on Myeloid Cells-1Blood‒brain barrierCognitive impairmentPI3K/AktSepsisTREM-1

Identifiers

PMID40426195
PMCPMC12117814

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.