Evaluation of Size-dependent Uptake, Transport and Cytotoxicity of Polystyrene Microplastic in a Blood-Brain Barrier (BBB) Model

Abstract

Microplastics, especially those in the micrometer range, can enter the human body via ingestion, inhalation, and skin contact. Recent studies suggest that they may affect the central nervous system (CNS) by crossing the blood-brain barrier (BBB), though the mechanisms behind their uptake and toxicity remain unclear. In this study, we used an engineered 3D human BBB model to evaluate the size-dependent uptake and cytotoxicity of polystyrene microparticles. Our results showed that 0.2 μm particles had significantly higher cellular uptake and transendothelial transport than 1.0 μm particles, leading to greater BBB permeability and cellular damage. After 24 hours of exposure, permeability increased 15.6-fold for 0.2 μm and 2-fold for 1.0 μm particles. At 72 hours, these values increased to 27.3-fold and 4.5-fold, respectively, compared to control. Furthermore, microplastic exposure after TNF-α stimulation led to even greater BBB absorption and damage, suggesting inflammation exacerbates toxicity. Importantly, the toxic effects differed between conventional 2D cultures and 3D BBB models, underscoring the relevance of physiologically representative systems in environmental toxicity assessments. Our findings highlight the potential for microplastics to compromise the BBB and suggest an urgent need for further investigation into their neurological impacts.