Tumour necrosis factor-α affects blood-brain barrier permeability and tight junction-associated occludin in acute liver failure

Abstract

Our results suggest that TNF-alpha plays a critical role in the development of brain oedema in ALF, and that both vasogenic and cytotoxic mechanisms may be involved. Increased BBB permeability may be because of the disruption of TJs, and loss of the TJ-associated protein occludin.

Brain edema in acute liver failure and chronic liver disease: Similarities and differences

“…In the same models, alterations in the expression of the major BBB tight junction proteins (occludin, claudin-5, zonula occludens 1 and 2) have been observed (Chen et al, 2009, Lv et al, 2010, Sawara et al, 2009and Shimojima et al, 2008. However, in galactosamine-induced ALF in the rabbit, it was reported that capillary endothelial cells appeared normal, and no evidence of brain extravasation to horseradish peroxidase was observed (Traber et al, 1987), contradicting the anterior data.…”

Cerebral Oxidative Stress and Microvasculature Defects in TNF-α Expressing Transgenic and Porphyromonas gingivalis-Infected ApoE–/– Mice

“…In addition, proinflammatory cytokines, such as TNF-α, IL-1β and IL-6, are relvant to early stages of AD onset [40]. From animal models, proinflammatory cytokines, such as TNF-α, are known to disturb inter-endothelial cell-cell connections and thereby cause BBB permeability [19]. This makes TNF-α transgenic mice [31] and ApoE -/-mice brains [27,29,30], ideal test models to investigate if they share common oxidative stress from an intrinsic biological (proinflammatory cytokine) stressor.…”

“…Inappropriate secretion of cytokines result in pro-oxidant mechanisms especially in neuroinflammatory pathologies. For example, TNF-α has been shown to permeabilise brain microvascular endothelial cells and degrade cell-cell adhesion proteins, such as occludin [19]; and it can induce ROS production in cultured cells [20].…”

The Virulence of 1997 H5N1 Influenza Viruses in the Mouse Model Is Increased by Correcting a Defect in Their NS1 Proteins

“…At day 1 postinfection, MCP-1 and TNF-␣ were increased in HK97G2ϩ-infected lungs compared to levels in wt-HK97-infected lungs. These two cytokines are known to increase pulmonary vascular permeability (29,32,37), which has previously been implicated in influenza virus pathogenesis (60). This early viremia would enable HK97G2ϩ to rapidly seed peripheral organs, such as the spleen, and subsequently spread to the brain, where cytokinemia may also increase the permeability of the blood-brain barrier, whereas the wild-type virus may be restricted to slower neurotropic spread through peripheral nerves.…”