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

N. TSAO, H.P. HSU, C.M. WU^*, C.C. LIU and H.Y. LEI

Departments of Microbiology and Immunology, *Anatomy and Paediatrics, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Corresponding author: Dr H.Y. Lei (e-mail: hylei{at}mail.ncku.edu.tw).

Received 24 Jan. 2001; revised version accepted 14 March 2001.

Abstract

Blood-brain barrier (BBB) permeability during sepsis with Escherichia coli or Streptococcus pneumoniae was examined in a mouse model and measured by a circulating ß-galactosidase tracer. The leakage of brain microvascular vessels during sepsis was confirmed by transmission electron microscopic examination of brain tissues stained with horseradish peroxidase. The increase of BBB permeability induced by E. coli and S. pneumoniae, which was maximal at 3 h and 12 h after injection, respectively, was transient because of rapid clearance of the bacteria from the blood. Tumour necrosis factor- (TNF-) was stained on microvascular vessels of the brain during sepsis and intravenous injection of recombinant TNF- also increased the BBB permeability. The increase in BBB permeability induced by either E. coli or S. pneumoniae could be inhibited by anti-TNF- antibody. It was concluded that circulating TNF- generated during sepsis induced the increase in BBB permeability.

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