ArticleCell research2015
P2RX7 sensitizes Mac-1/ICAM-1-dependent leukocyte-endothelial adhesion and promotes neurovascular injury during septic encephalopathy.
Article in Cell research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 2 of them syntheses that pooled it.
What it found
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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.
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.
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Who cites it
70 citing papers in PubMed, 2 syntheses or guidelines pooled it, 125 citations in OpenAlex.
- Risk factors for unexplained early neurological deterioration after intravenous thrombolysis: a meta-analysis.Neurosciences (Riyadh, Saudi Arabia) · 2025Pooled it
- The Key Drivers of Brain Injury by Systemic Inflammatory Responses after Sepsis: Microglia and Neuroinflammation.Molecular neurobiology · 2023Pooled it
- Target degradation of CASPASE-1 for alleviation of inflammation in sepsisActa pharmaceutica Sinica. B · 2026Article
- Aging, the microbiota-gut-brain axis, and late-life epilepsy: a hypothesis-driven review.Frontiers in molecular neuroscience · 2026Review
- Research article proteomics-based plasma biomarkers for predicting CRKP infection in ICU sepsis patients.Frontiers in pharmacology · 2026Article
- Mesenchymal stem cells in sepsis-induced organ dysfunction: mechanisms and therapeutic potential.Stem cell research & therapy · 2025Review
- The role of maternal infections in neurodevelopmental psychiatric disorders: focus on the P2X7/NLRP3/IL-1β signalling pathway.Journal of neuroinflammation · 2025Review
- Partial depletion of circulating neutrophil granulocytes in mice exacerbates the inflammatory response and hypothermia during LPS induced severe systemic inflammation.Frontiers in immunology · 2025Article
- Targeting P2X Receptors-Current Progress in Sepsis.International journal of inflammation · 2025Review
- Mac-1 blockade impedes adhesion-dependent neutrophil extracellular trap formation and ameliorates lung injury in LPS-induced sepsis.Frontiers in immunology · 2025Article
- Cerebral endothelial 3-mercaptopyruvate sulfurtransferase improves ischemia-induced cognitive impairmentActa pharmaceutica Sinica. B · 2025Article
- Targeting Brain Endothelial Gasdermin D: A Shortcut to Remodel the Blood-Brain Barrier.Neuroscience bulletin · 2025Article
- Hematopoietic Growth Factors Regulate the Entry of Monocytes into the Adult Brain via Chemokine Receptor CCR5.International journal of molecular sciences · 2024Article
- Article
- Review
- Distinct Olfactory Bulb-Cortex Neural Circuits Coordinate Cognitive Function in Parkinson's Disease.Research (Washington, D.C.) · 2024Article
- P2X7 receptor: A receptor closely linked with sepsis-associated encephalopathy.Open life sciences · 2024Review
- Single-cell RNA sequencing unveils Lrg1's role in cerebral ischemia‒reperfusion injury by modulating various cells.Journal of neuroinflammation · 2023Article
- Endothelial TFEB signaling-mediated autophagic disturbance initiates microglial activation and cognitive dysfunction.Autophagy · 2023Article
- Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Septic encephalopathy (SE) is a critical factor determining sepsis mortality. Vascular inflammation is known to be involved in SE, but the molecular events that lead to the development of encephalopathy remain unclear. Using time-lapse in vivo two-photon laser scanning microscopy, we provide the first direct evidence that cecal ligation and puncture in septic mice induces microglial trafficking to sites adjacent to leukocyte adhesion on inflamed cerebral microvessels. Our data further demonstrate that septic injury increased the chemokine CXCL1 level in brain endothelial cells by activating endothelial P2RX7 and eventually enhanced the binding of Mac-1 (CD11b/CD18)-expressing leukocytes to endothelial ICAM-1. In turn, leukocyte adhesion upregulated endothelial CX3CL1, thereby triggering microglia trafficking to the injured site. The sepsis-induced increase in endothelial CX3CL1 was abolished in CD18 hypomorphic mutant mice. Inhibition of the P2RX7 pathway not only decreased endothelial ICAM-1 expression and leukocyte adhesion but also prevented microglia overactivation, reduced brain injury, and consequently doubled the early survival of septic mice. These results demonstrate the role of the P2RX7 pathway in linking neurovascular inflammation to brain damage in vivo and provide a rationale for targeting endothelial P2RX7 for neurovascular protection during SE.
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Registered trials
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.