ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Matrix metalloprotease 8-dependent extracellular matrix cleavage at the blood-CSF barrier contributes to lethality during systemic inflammatory diseases.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 2 of them syntheses that pooled it.
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Who cites it
75 citing papers in PubMed, 2 syntheses or guidelines pooled it, 111 citations in OpenAlex.
- The Key Drivers of Brain Injury by Systemic Inflammatory Responses after Sepsis: Microglia and Neuroinflammation.Molecular neurobiology · 2023Pooled it
- Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies.The Lancet. Neurology · 2014Pooled it
- Matrix Metalloproteinase-8 Deficiency Alters the Balance Between Viral Clearance and Immunopathology in H1N1 Infection.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- CAR design equips diverse immune cells with unique antigen-specific activation identities.Molecular therapy. Oncology · 2026Article
- Identification of core differentially expressed genes for respiratory syncytial virus infection.Global medical genetics · 2026Article
- Opposing prognostic roles of tumor-associated and circulating MMP8 in colorectal cancer.Clinical and experimental medicine · 2026Article
- Cross-Organ Neuroimmunology of Behavior.Annual review of immunology · 2026Review
- Base barrier cells provide compartmentalization of choroid plexus, brain and CSF.Nature neuroscience · 2026Article
- Altered epithelial development of the lateral ventricle choroid plexus in Mllt11 mutants.Biology open · 2025Article
- The influence of the choroid plexus on brain function: beyond its role in cerebrospinal fluid production.Inflammation and regeneration · 2025Review
- A shared inflammatory signature across severe malaria syndromes manifested by transcriptomic, proteomic and metabolomic analyses.Nature communications · 2025Article
- Knowns and unknowns of TiLV-associated neuronal disease.Virulence · 2024Review
- Paneth cell TNF signaling induces gut bacterial translocation and sepsis.Cell host & microbe · 2024Article
- The Spreading and Effects of Human Recombinant α-Synuclein Preformed Fibrils in the Cerebrospinal Fluid of Mice.eNeuro · 2024Article
- Unraveling the fatigue puzzle: insights into the pathogenesis and management of IBD-related fatigue including the role of the gut-brain axis.Frontiers in medicine · 2024Review
- Approaches for Increasing Cerebral Efflux of Amyloid-β in Experimental Systems.Journal of Alzheimer's disease : JAD · 2024Review
- Dengue virus infection induces selective expansion of Vγ4 and Vγ6TCR γδ T cells in the small intestine and a cytokine storm driving vascular leakage in mice.PLoS neglected tropical diseases · 2023Article
- Gut microbiota regulates blood-cerebrospinal fluid barrier function and Aβ pathology.The EMBO journal · 2023Article
- Helicobacter pylori-derived outer membrane vesicles contribute to Alzheimer's disease pathogenesis via C3-C3aR signalling.Journal of extracellular vesicles · 2023Article
- A Journey to the Central Nervous System: Routes of Flaviviral Neuroinvasion in Human Disease.Viruses · 2022Review
15 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 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Systemic inflammatory response syndrome (SIRS) is a highly mortal inflammatory disease, associated with systemic inflammation and organ dysfunction. SIRS can have a sterile cause or can be initiated by an infection, called sepsis. The prevalence is high, and available treatments are ineffective and mainly supportive. Consequently, there is an urgent need for new treatments. The brain is one of the first organs affected during SIRS, and sepsis and the consequent neurological complications, such as encephalopathy, are correlated with decreased survival. The choroid plexus (CP) that forms the blood-CSF barrier (BCSFB) is thought to act as a brain "immune sensor" involved in the communication between the peripheral immune system and the CNS. Nevertheless, the involvement of BCSFB integrity in systemic inflammatory diseases is seldom investigated. We report that matrix metalloprotease-8 (MMP8) depletion or inhibition protects mice from death and hypothermia in sepsis and renal ischemia/reperfusion. This effect could be attributed to MMP8-dependent leakage of the BCSFB, caused by collagen cleavage in the extracellular matrix of CP cells, which leads to a dramatic change in cellular morphology. Disruption of the BCSFB results in increased CSF cytokine levels, brain inflammation, and downregulation of the brain glucocorticoid receptor. This receptor is necessary for dampening the inflammatory response. Consequently, MMP8(+/+) mice, in contrast to MMP8(-/-) mice, show no anti-inflammatory response and this results in high mortality. In conclusion, we identify MMP8 as an essential mediator in SIRS and, hence, a potential drug target. We also propose that the mechanism of action of MMP8 involves disruption of the BCSFB integrity.
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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.