Tumor necrosis factor-alpha mediates the blood-brain barrier dysfunction induced by activated microglia in mouse brain microvascular endothelial cells.

The present study was designed to elucidate the involvement of tumor necrosis factor-alpha (TNF-alpha) release from activated microglia in the induction of blood-brain barrier (BBB) dysfunction in an in vitro co-culture system with mouse brain capillary endothelial cells (MBEC4) and microglia. Lipopolysaccharide (LPS)-activated microglia increased the permeability of MBEC4 cells to sodium-fluorescein, and this hyper-permeability was blocked by a neutralizing antibody against TNF-alpha. LPS stimulated microglia to facilitate TNF-alpha release. These findings suggested that TNF-alpha released from activated microglia is attributable to BBB dysfunction.