| Summary: | Although it has been reported that blood brain barrier (BBB) disruption following head impact can lead to increased vascular permeability and subsequent brain injury, the influence of pressure loading on BBB dysfunction is not fully understood. In this study, we exposed in vitro BBB models to impulsive pressure to mimic changes in intracranial pressure during head impact. Barrier function was examined by measuring transendothelial electrical resistance (TEER). Four models were used: an endothelial monolayer of rat brain capillaries (E00 model), a co-culture model of endothelial cells and pericytes (EP0 model), a co-culture model of endothelial cells and astrocytes (EA0 model), and a triple co-culture model of endothelial cells, pericytes, and astrocytes (EPA model). Immediately after loading, the E00 model showed a 13% decrease in TEER, the EP0 model showed an 8% decrease, the EA0 model showed a 40% decrease, and the EPA model showed a 33% decrease. At 2 days post-loading, TEER values in the EPA model remained decreased and the expression of claudin-5 and ZO-1 was significantly decreased, whereas GFAP expression was significantly increased. In conclusion, increased endothelial paracellular permeability induced by exposure to impulsive pressure is associated with astrocyte activation and decreased tight junction protein expression in vitro.
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