ArticleFluids and barriers of the CNS2021
Comparative assessment of in vitro BBB tight junction integrity following exposure to cigarette smoke and e-cigarette vapor: a quantitative evaluation of the protective effects of metformin using small-molecular-weight paracellular markers.
Article in Fluids and barriers of the CNS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Effects of cigarette smoke and HIV-1 factors on blood-brain barrier integrity and permeability in an in vitro model.Journal of neurovirology · 2026Article
- Organ-specific apoptotic pathways induced by micro- and nanoplastics: a systematic review ofFrontiers in toxicology · 2026Review
- Tight junction suppression by candidalysin promotes gut-to-blood dissemination ofFrontiers in microbiology · 2026Article
- Cigarette smoke-induced lung-brain barrier dysfunction drives neurocognitive impairment via inflammatory spill-over.Journal of neuroinflammation · 2025Article
- The Breakdown of Neurovascular Barriers: Molecular Mechanisms of Tight Junction Dysfunction.Molecular neurobiology · 2025Review
- Metformin's protection against blood-brain barrier disruption and neuronal dysfunction under oxygen-glucose deprivation and tobacco smoke and e-vape chemical exposure.Fluids and barriers of the CNS · 2025Article
- Oxidative Stress in HIV-Associated Neurodegeneration: Mechanisms of Pathogenesis and Therapeutic Targets.International journal of molecular sciences · 2025Review
- Neuroprotective Effects of Metformin Through the Modulation of Neuroinflammation and Oxidative Stress.Cells · 2025Review
- Mesenchymal stem cell-derived exosomes-a promising therapeutic approach to improve neurocognitive disorders in chronic obstructive pulmonary disease.Stem cell research & therapy · 2025Review
- Evaluation of systemic and brain pharmacokinetic parameters for repurposing metformin using intravenous bolus administration.The Journal of pharmacology and experimental therapeutics · 2025Article
- Eucalyptus Wood Smoke Extract Elicits a Dose-Dependent Effect in Brain Endothelial Cells.International journal of molecular sciences · 2024Article
- Metformin ameliorates neuroinflammatory environment for neurons and astrocytes during in vitro and in vivo stroke and tobacco smoke chemical exposure: Role of Nrf2 activation.Redox biology · 2024Article
- The Acute Impact of Propofol on Blood-Brain Barrier Integrity in Mice.Pharmaceutical research · 2024Article
- The Progress in Molecular Transport and Therapeutic Development in Human Blood-Brain Barrier Models in Neurological Disorders.Cellular and molecular neurobiology · 2024Review
- Higher Brain Uptake of Gentamicin and Ceftazidime under Isoflurane Anesthesia Compared to Ketamine/Xylazine.Pharmaceutics · 2024Article
- Permeability of Metformin across an In Vitro Blood-Brain Barrier Model during Normoxia and Oxygen-Glucose Deprivation Conditions: Role of Organic Cation Transporters (Octs).Pharmaceutics · 2023Article
- Maternal e-cigarette use can disrupt postnatal blood-brain barrier (BBB) integrity and deteriorates motor, learning and memory function: influence of sex and age.Fluids and barriers of the CNS · 2023Article
- Impact of Electronic Cigarette Vaping on Cerebral Ischemia: What We Know So Far.Translational stroke research · 2022Review
- Metformin Preserves VE-Cadherin in Choroid Plexus and Attenuates Hydrocephalus via VEGF/VEGFR2/p-Src in an Intraventricular Hemorrhage Rat Model.International journal of molecular sciences · 2022Article
- Vascularizing the brainiScience · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe blood-brain barrier (BBB) plays a critical role in protecting the central nervous system (CNS) from blood-borne agents and potentially harmful xenobiotics. Our group's previous data has shown that tobacco smoke (TS) and electronic cigarettes (EC) affect the BBB integrity, increase stroke incidence, and are considered a risk factor for multiple CNS disorders. Metformin was also found to abrogate the adverse effects of TS and EC.
methodsWe used sucrose and mannitol as paracellular markers to quantitatively assess TS and EC's impact on the BBB in-vitro. Specifically, we used a quantitative platform to determine the harmful effects of smoking on the BBB and study the protective effect of metformin. Using a transwell system and iPSCs-derived BMECs, we assessed TS and EC's effect on sucrose and mannitol permeability with and without metformin pre-treatment at different time points. Concurrently, using immunofluorescence (IF) and Western blot (WB) techniques, we evaluated the expression and distribution of tight junction proteins, including ZO-1, occludin, and claudin-5.
resultsOur data showed that TS and EC negatively affect sucrose and mannitol permeability starting after 6 h and up to 24 h. The loss of barrier integrity was associated with a reduction of TEER values. While the overall expression level of ZO-1 and occludin was not significantly downregulated, the distribution of ZO-1 was altered, and discontinuation patterns were evident through IF imaging. In contrast to occludin, claudin-5 expression was significantly decreased by TS and EC, as demonstrated by WB and IF data.
conclusionIn agreement with previous studies, our data showed the metformin could counteract the negative impact of TS and EC on BBB integrity, thus suggesting the possibility of repurposing this drug to afford cerebrovascular protection.
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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.