ArticleOxidative medicine and cellular longevity2021
Increase in Blood-Brain Barrier (BBB) Permeability Is Regulated by MMP3 via the ERK Signaling Pathway.
Article in Oxidative medicine and cellular longevity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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.
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.
Who cites it
41 citing papers in PubMed, 53 citations in OpenAlex.
- Brief, Repeated Isoflurane Anaesthesia Elicits Sex-Dependent Behavioural, Cerebrovascular and Microglial Alterations in Mice.The European journal of neuroscience · 2026Article
- Spatiotemporal arising of molecular and functional blood-brain barrier properties in the developing Gallus gallus optic tectum.Fluids and barriers of the CNS · 2026Article
- The extracellular matrix as a dynamic regulator of brain function and plasticity.Neurobiology of disease · 2026Review
- Review
- Neuroinflammation and blood-brain barrier dysfunction in cerebral small vessel disease: mechanisms, biomarkers, and therapeutic implications.European journal of medical research · 2026Review
- Minimally Invasive Endovascular Administration for Targeted PLGA Nanoparticles Delivery to Brain, Salivary Glands, Kidney and Lower Limbs.Pharmaceutics · 2026Article
- Prenatal Exposure to Tobacco Smoke and Vaping Aerosols: Mechanisms Disrupting White-Matter Formation.Toxics · 2025Review
- Mechanistic Interplay of Gut Microbiota and Blood-Brain Barrier Integrity in Neurodegenerative Diseases.Molecular neurobiology · 2025Review
- Purinergic and extracellular vesicle signaling in alcohol-induced blood-brain barrier breakdown and neuroimmune activation.Brain, behavior, and immunity · 2025Review
- Role of transforming growth factorβ in neurovascular unit during cerebral small vessel disease.Fluids and barriers of the CNS · 2025Review
- Protective Effects of Luteolin onAntibiotics (Basel, Switzerland) · 2025Article
- Modular-Based Synergetic Mechanisms of Jasminoidin and Ursodeoxycholic Acid in Cerebral Ischemia Therapy.Biomedicines · 2025Article
- Dual Challenges in the Context of Healthy Aging: A Comprehensive Exploration of the Association between Malnutrition and Cognitive Decline in Disabled Elderly.Aging and disease · 2025Review
- Ulinastatin treatment mitigates glycocalyx degradation and associated with lower postoperative delirium risk in patients undergoing cardiac surgery: a multicentre observational study.Critical care (London, England) · 2025Observational
- Methylene Blue Pretreatment Protects Against Repeated Neonatal Isoflurane Exposure-Induced Brain Injury and Memory Loss.Molecular neurobiology · 2024Article
- Infliximab modifies CD74-mediated lymphatic abnormalities and adipose tissue alterations in creeping fat of Crohn's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Ibrutinib disrupts blood-tumor barrier integrity and prolongs survival in rodent glioma model.Acta neuropathologica communications · 2024Article
- Vascular dysfunction in sporadic bvFTD: white matter hyperintensity and peripheral vascular biomarkers.Alzheimer's research & therapy · 2024Article
- Beyond the barrier: the immune-inspired pathways of tumor extravasation.Cell communication and signaling : CCS · 2024Review
- Ischemia-induced endogenous Nrf2/HO-1 axis activation modulates microglial polarization and restrains ischemic brain injury.Frontiers in immunology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe blood-brain barrier (BBB) regulates the exchange of molecules between the brain and peripheral blood and is composed primarily of microvascular endothelial cells (BMVECs), which form the lining of cerebral blood vessels and are linked via tight junctions (TJs). The BBB is regulated by components of the extracellular matrix (ECM), and matrix metalloproteinase 3 (MMP3) remodels the ECM's basal lamina, which forms part of the BBB. Oxidative stress is implicated in activation of MMPs and impaired BBB. Thus, we investigated whether MMP3 modulates BBB permeability.
methodsExperiments included
resultsCompared to WT mice, measurements of isoflurane usage and anesthesia induction time were higher in MMP3-KO mice and lower in WT that had been treated with MMP3 (WT+MMP3), while anesthesia emergence times were shorter in MMP3-KO mice and longer in WT+MMP3 mice than in WT. Extravasation of systemically administered dyes was also lower in MMP3-KO mouse brains and higher in WT+MMP3 mouse brains, than in the brains of WT mice. The results from both TEER and Transwell assays indicated that MMP3 deficiency (or inhibition) increased, while MMP3 upregulation reduced barrier integrity in either BMVEC or the coculture. MMP3 deficiency also increased the abundance of TJs and VE-cadherin proteins in BMVECs, and the protein abundance declined when MMP3 activity was upregulated in BMVECs, but not when the cells were treated with an inhibitor of extracellular signal related-kinase (ERK).
conclusionMMP3 increases BBB permeability following the administration of isoflurane by upregulating the ERK signaling pathway, which subsequently reduces TJ and VE-cadherin proteins in BMVECs.
Indexed as
Identifiers
What OpenQuestion holds
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.