Blood–brain barrier in acute liver failure

Brain edema remains a challenging obstacle in the management of acute liver failure (ALF). Cytotoxic mechanisms associated with brain edema have been well recognized, but evidence for vasogenic mechanisms in the pathogenesis of brain edema in ALF has been lacking. Recent reports have not only shown a role of matrix metalloproteinase-9 in the pathogenesis of brain edema in experimental ALF but have also found significant alterations in the tight junction elements including occludin and claudin-5, suggesting a vasogenic injury in the blood–brain barrier (BBB) integrity. This article reviews and explores the role of the paracellular tight junction proteins in the increased selective BBB permeability that leads to brain edema in ALF.

► Brain edema in ALF occurs with BBB dysfunction without overt structural breakdown. ► Recent evidences suggest that peripheral MMP-9 can induce subtle BBB perturbation. ► EGFR and p38 MAPK signalings contribute to paracellular permeability across BBB in ALF.