Wen Wang1, Sa Lv, Ying Zhou, Jinlong Fu, Chengbo Li, Pei Liu. 1. Department of Infectious Diseases, the First Affiliated Hospital, China Medical University, No. 55 Nanjing Street, Shenyang, Liaoning Province, China.
Abstract
OBJECTIVES: 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. MATERIALS AND 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. CONCLUSION: 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.
OBJECTIVES: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. MATERIALS AND 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 ALFmice 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 ALFmice. Changes in BBB permeability and occludin expression could be prevented by administering anti-TNFα-IgG 2 h after APAP challenge. CONCLUSION: 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: Junie P Warrington; Heather A Drummond; Joey P Granger; Michael J Ryan Journal: Am J Physiol Regul Integr Comp Physiol Date: 2015-09-23 Impact factor: 3.619
Authors: Charlene E Gamaldo; Alyssa Gamaldo; Jason Creighton; Rachel E Salas; Ola A Selnes; Paula M David; Gilbert Mbeo; Benjamin S Parker; Amanda Brown; Justin C McArthur; Michael T Smith Journal: J Acquir Immune Defic Syndr Date: 2013-08-15 Impact factor: 3.731
Authors: F Xing; S Sharma; Y Liu; Y-Y Mo; K Wu; Y-Y Zhang; R Pochampally; L A Martinez; H-W Lo; K Watabe Journal: Oncogene Date: 2015-02-09 Impact factor: 9.867
Authors: Wesam Gamal; Philipp Treskes; Kay Samuel; Gareth J Sullivan; Richard Siller; Vlastimil Srsen; Katie Morgan; Anna Bryans; Ada Kozlowska; Andreas Koulovasilopoulos; Ian Underwood; Stewart Smith; Jorge Del-Pozo; Sharon Moss; Alexandra Inés Thompson; Neil C Henderson; Peter C Hayes; John N Plevris; Pierre-Olivier Bagnaninchi; Leonard J Nelson Journal: Sci Rep Date: 2017-01-30 Impact factor: 4.379
Authors: Jacquelyn A Brown; Simona G Codreanu; Mingjian Shi; Stacy D Sherrod; Dmitry A Markov; M Diana Neely; Clayton M Britt; Orlando S Hoilett; Ronald S Reiserer; Philip C Samson; Lisa J McCawley; Donna J Webb; Aaron B Bowman; John A McLean; John P Wikswo Journal: J Neuroinflammation Date: 2016-12-12 Impact factor: 8.322