Tumour necrosis factor-alpha causes an increase in blood-brain barrier permeability during sepsis

Blood-brain barrier (BBB) permeability during sepsis with Escherichia coli or Streptococcus pneumoniae was examined in a mouse model and measured by a circulating beta -galactosidase tracer. The leakage of brain microvascular vessels during sepsis was confirmed by transmission electron microscopic e xamination of brain tissues stained with horseradish peroxidase. The increa se of BBB permeability induced by E. coli and S. pneumoniae, which was maxi mal at 3 h and 12 h after injection, respectively, was transient because of rapid clearance of the bacteria from the blood. Tumour necrosis factor-alp ha (TNF-alpha) was stained on microvascular vessels of the brain during sep sis and intravenous injection of recombinant TNF-alpha also increased the B BB permeability. The increase in BBB permeability induced by either E. coli or S. pneumoniae could be inhibited by anti-TNF-alpha antibody. It was con cluded that circulating TNF-alpha generated during sepsis induced the incre ase in BBB permeability.