title: Tumor necrosis factor-α affects blood-brain barrier permeability in acetaminophen-induced acute liver failure.
abstract: OBJECTIVE
  Cerebral edema is a major cause of death during acute liver failure (ALF), but the exact mechanism of this condition is still not entirely clear. The aim of this study was to investigate the role of tumor necrosis factor α (TNFα) in changing the permeability of the blood-brain barrier (BBB) during acetaminophen (APAP)-induced ALF.
  
  
  METHODS
  ALF animal models were generated by administering APAP. Anti-TNFα-IgG was intravenously injected (100 μg/mouse) 2 h after administration of APAP. We investigated BBB permeability with Evans blue staining, and structure with electron microscopy.
  
  
  RESULTS
  BBB permeability increased in APAP-induced ALF mice and correlated with elevated serum TNFα levels. Electron microscopy of mouse brain tissues revealed tight junction (TJ) disruptions and endothelial cell shrinkage, as well as increased vesicles and vacuoles. In addition, the expression of the TJ-associated protein, occludin, was significantly decreased in APAP-induced ALF mice. Changes in BBB permeability and occludin expression could be prevented by administering anti-TNFα-IgG 2 h after APAP challenge.
  
  
  CONCLUSIONS
  TNFα plays a critical role in the development of brain edema in APAP-induced ALF. Increased BBB permeability may be due to the loss of the TJ-associated protein occludin.
authors: Department of Infectious Diseases, the First Affiliated Hospital, China Medical University, No. 55 Nanjing Street, Shenyang, Liaoning Province, China.
authors: Wen
authors: W
authors: Wang
authors: Sa
authors: S
authors: Lv
authors: Ying
authors: Y
authors: Zhou
authors: Jinlong
authors: J
authors: Fu
authors: Chengbo
authors: C
authors: Li
authors: Pei
authors: P
authors: Liu