ArticleInternational journal of nanomedicine2015
Silver nanoparticles induce tight junction disruption and astrocyte neurotoxicity in a rat blood-brain barrier primary triple coculture model.
Article in International journal of nanomedicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 112 citations in OpenAlex.
- Silver Nanoparticles and Neurotoxicity: Mechanistic Insights and Recent Experimental Evidence.Pharmaceutics · 2026Review
- Oxidative stress-driven disease-associated microglia (DAM)-like polarization in human microglia (HMC3) cells exposed to small-size silver nanoparticles in a transwell co-culture system with neurons (cholinergic differentiated SH-SY5Y) cells in vitro.Archives of toxicology · 2026Article
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- Cardiovascular Toxicity of Metal-Based Nanoparticles.International journal of molecular sciences · 2025Review
- Assessing cytotoxicity and endoplasmic reticulum stress in human blood-brain barrier cells due to silver and copper oxide nanoparticles.Journal of applied genetics · 2025Article
- Astrocyte-mediated inflammatory responses in traumatic brain injury: mechanisms and potential interventions.Frontiers in immunology · 2025Review
- Argyria and Neuropsychiatric Disorders: When not only the Matter is Gray. A Literature Review and a Case Report.Current medicinal chemistry · 2025Review
- Orally Administered Silver Nanoparticles Are Absorbed and Migrate to Testes in Mice.ACS nanoscience Au · 2024Article
- Sodium Selenite Ameliorates Silver Nanoparticles Induced Vascular Endothelial Cytotoxic Injury by Antioxidative Properties and Suppressing Inflammation Through Activating the Nrf2 Signaling Pathway.Biological trace element research · 2024Article
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- Silver Compounds for Caries Management.International dental journal · 2024Review
- Noradrenaline release from the locus coeruleus shapes stress-induced hippocampal gene expression.eLife · 2024Article
- Ag- but Not ZnO-Nanoparticles Disturb the Airway Epithelial Barrier at Subtoxic Concentrations.Pharmaceutics · 2023Article
- Long-term application of silver nanoparticles in dental restoration materials: potential toxic injury to the CNS.Journal of materials science. Materials in medicine · 2023Review
- Storming the gate: New approaches for targeting the dynamic tight junction for improved drug delivery.Advanced drug delivery reviews · 2023Review
- Determinants and mechanisms of inorganic nanoparticle translocation across mammalian biological barriers.Archives of toxicology · 2023Review
- Effective decolonization strategy for mupirocin-resistantMaterials today. Bio · 2023Article
- Potentially toxic elements in the brains of people with multiple sclerosis.Scientific reports · 2023Article
- Article
- Functionalized Noble Metal Nanoparticles for the Treatment of Herpesvirus Infection.Microorganisms · 2022Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSilver nanoparticles (Ag-NPs) can enter the brain and induce neurotoxicity. However, the toxicity of Ag-NPs on the blood-brain barrier (BBB) and the underlying mechanism(s) of action on the BBB and the brain are not well understood.
methodTo investigate Ag-NP suspension (Ag-NPS)-induced toxicity, a triple coculture BBB model of rat brain microvascular endothelial cells, pericytes, and astrocytes was established. The BBB permeability and tight junction protein expression in response to Ag-NPS, NP-released Ag ions, and polystyrene-NP exposure were investigated. Ultrastructural changes of the microvascular endothelial cells, pericytes, and astrocytes were observed using transmission electron microscopy (TEM). Global gene expression of astrocytes was measured using a DNA microarray.
resultsA triple coculture BBB model of primary rat brain microvascular endothelial cells, pericytes, and astrocytes was established, with the transendothelial electrical resistance values >200 Ω·cm(2). After Ag-NPS exposure for 24 hours, the BBB permeability was significantly increased and expression of the tight junction (TJ) protein ZO-1 was decreased. Discontinuous TJs were also observed between microvascular endothelial cells. After Ag-NPS exposure, severe mitochondrial shrinkage, vacuolations, endoplasmic reticulum expansion, and Ag-NPs were observed in astrocytes by TEM. Global gene expression analysis showed that three genes were upregulated and 20 genes were downregulated in astrocytes treated with Ag-NPS. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the 23 genes were associated with metabolic processes, biosynthetic processes, response to stimuli, cell death, the MAPK pathway, and so on. No GO term and KEGG pathways were changed in the released-ion or polystyrene-NP groups. Ag-NPS inhibited the antioxidant defense of the astrocytes by increasing thioredoxin interacting protein, which inhibits the Trx system, and decreasing Nr4a1 and Dusp1. Meanwhile, Ag-NPS induced inflammation and apoptosis through modulation of the MAPK pathway or B-cell lymphoma-2 expression or mTOR activity in astrocytes.
conclusionThese results draw our attention to the importance of Ag-NP-induced toxicity on the neurovascular unit and provide a better understanding of its toxicological mechanisms on astrocytes.
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