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

Microplastics, particularly those in the micrometer scale, have been shown to enter the human body through ingestion, inhalation, and dermal contact. Recent research indicates that microplastics can potentially impact the central nervous system (CNS) by crossing the blood-brain barrier (BBB). However, the exact mechanisms of their transport, uptake, and subsequent toxicity at BBB remain unclear. In this study, we evaluated the size-dependent uptake and cytotoxicity of polystyrene microparticles using an engineered BBB model. Our findings demonstrate that 0.2 μm polystyrene microparticles exhibit significantly higher uptake and transendothelial transport compared to 1.0 μm polystyrene microparticles, leading to increased permeability and cellular damage. After 24 h of exposure, permeability increased by 15.6-fold for the 0.2 μm particles and 2-fold for the 1.0 μm particles compared to the control. After 72 h of exposure, permeability further increased by 27.3-fold for the 0.2 μm particles and a 4.5-fold for the 1.0 μm particles compared to the control. Notably, microplastics administration following TNF-α treatment resulted in enhanced absorption and greater BBB damage compared to non-stimulated conditions. Additionally, the size-dependent toxicity observed differently between 2D cultured cells and 3D BBB models, highlighting the importance of testing models in evaluating environmental toxicity.